Daily Papers

Drug toxicity remains a major challenge in pharmaceutical development. Recent machine learning models have improved in silico toxicity prediction, but their reliance on annotated data and lack of interpretability limit their applicability. This limits their ability to capture organ-specific toxicities driven by complex biological mechanisms. Large language models (LLMs) offer a promising alternative through step-by-step reasoning and integration of textual data, yet prior approaches lack biological context and transparent rationale. To address this issue, we propose CoTox, a novel framework that integrates LLM with chain-of-thought (CoT) reasoning for multi-toxicity prediction. CoTox combines chemical structure data, biological pathways, and gene ontology (GO) terms to generate interpretable toxicity predictions through step-by-step reasoning. Using GPT-4o, we show that CoTox outperforms both traditional machine learning and deep learning model. We further examine its performance across various LLMs to identify where CoTox is most effective. Additionally, we find that representing chemical structures with IUPAC names, which are easier for LLMs to understand than SMILES, enhances the model's reasoning ability and improves predictive performance. To demonstrate its practical utility in drug development, we simulate the treatment of relevant cell types with drug and incorporated the resulting biological context into the CoTox framework. This approach allow CoTox to generate toxicity predictions aligned with physiological responses, as shown in case study. This result highlights the potential of LLM-based frameworks to improve interpretability and support early-stage drug safety assessment. The code and prompt used in this work are available at https://github.com/dmis-lab/CoTox.

Recent advances in large language models (LLMs) have led to their extensive global deployment, and ensuring their safety calls for comprehensive and multilingual toxicity evaluations. However, existing toxicity benchmarks are overwhelmingly focused on English, posing serious risks to deploying LLMs in other languages. We address this by introducing PolygloToxicityPrompts (PTP), the first large-scale multilingual toxicity evaluation benchmark of 425K naturally occurring prompts spanning 17 languages. We overcome the scarcity of naturally occurring toxicity in web-text and ensure coverage across languages with varying resources by automatically scraping over 100M web-text documents. Using PTP, we investigate research questions to study the impact of model size, prompt language, and instruction and preference-tuning methods on toxicity by benchmarking over 60 LLMs. Notably, we find that toxicity increases as language resources decrease or model size increases. Although instruction- and preference-tuning reduce toxicity, the choice of preference-tuning method does not have any significant impact. Our findings shed light on crucial shortcomings of LLM safeguarding and highlight areas for future research.

Foundation models applied to bio-molecular space hold promise to accelerate drug discovery. Molecular representation is key to building such models. Previous works have typically focused on a single representation or view of the molecules. Here, we develop a multi-view foundation model approach, that integrates molecular views of graph, image and text. Single-view foundation models are each pre-trained on a dataset of up to 200M molecules and then aggregated into combined representations. Our multi-view model is validated on a diverse set of 18 tasks, encompassing ligand-protein binding, molecular solubility, metabolism and toxicity. We show that the multi-view models perform robustly and are able to balance the strengths and weaknesses of specific views. We then apply this model to screen compounds against a large (>100 targets) set of G Protein-Coupled receptors (GPCRs). From this library of targets, we identify 33 that are related to Alzheimer's disease. On this subset, we employ our model to identify strong binders, which are validated through structure-based modeling and identification of key binding motifs.

Pretraining datasets are foundational to the development of multimodal models, yet they often have inherent biases and toxic content from the web-scale corpora they are sourced from. In this paper, we investigate the prevalence of toxicity in LLaVA image-text pretraining dataset, examining how harmful content manifests in different modalities. We present a comprehensive analysis of common toxicity categories and propose targeted mitigation strategies, resulting in the creation of a refined toxicity-mitigated dataset. This dataset removes 7,531 of toxic image-text pairs in the LLaVA pre-training dataset. We offer guidelines for implementing robust toxicity detection pipelines. Our findings underscore the need to actively identify and filter toxic content - such as hate speech, explicit imagery, and targeted harassment - to build more responsible and equitable multimodal systems. The toxicity-mitigated dataset is open source and is available for further research.

The discourse around toxicity and LLMs in NLP largely revolves around detection tasks. This work shifts the focus to evaluating LLMs' reasoning about toxicity -- from their explanations that justify a stance -- to enhance their trustworthiness in downstream tasks. Despite extensive research on explainability, it is not straightforward to adopt existing methods to evaluate free-form toxicity explanation due to their over-reliance on input text perturbations, among other challenges. To account for these, we propose a novel, theoretically-grounded multi-dimensional criterion, Human-Aligned Faithfulness (HAF), that measures the extent to which LLMs' free-form toxicity explanations align with those of a rational human under ideal conditions. We develop six metrics, based on uncertainty quantification, to comprehensively evaluate \haf of LLMs' toxicity explanations with no human involvement, and highlight how "non-ideal" the explanations are. We conduct several experiments on three Llama models (of size up to 70B) and an 8B Ministral model on five diverse toxicity datasets. Our results show that while LLMs generate plausible explanations to simple prompts, their reasoning about toxicity breaks down when prompted about the nuanced relations between the complete set of reasons, the individual reasons, and their toxicity stances, resulting in inconsistent and nonsensical responses. We open-source our code and LLM-generated explanations at https://github.com/uofthcdslab/HAF.

Toxicity remains a leading cause of early-stage drug development failure. Despite advances in molecular design and property prediction, the task of molecular toxicity repair - generating structurally valid molecular alternatives with reduced toxicity - has not yet been systematically defined or benchmarked. To fill this gap, we introduce ToxiMol, the first benchmark task for general-purpose Multimodal Large Language Models (MLLMs) focused on molecular toxicity repair. We construct a standardized dataset covering 11 primary tasks and 560 representative toxic molecules spanning diverse mechanisms and granularities. We design a prompt annotation pipeline with mechanism-aware and task-adaptive capabilities, informed by expert toxicological knowledge. In parallel, we propose an automated evaluation framework, ToxiEval, which integrates toxicity endpoint prediction, synthetic accessibility, drug-likeness, and structural similarity into a high-throughput evaluation chain for repair success. We systematically assess nearly 30 mainstream general-purpose MLLMs and design multiple ablation studies to analyze key factors such as evaluation criteria, candidate diversity, and failure attribution. Experimental results show that although current MLLMs still face significant challenges on this task, they begin to demonstrate promising capabilities in toxicity understanding, semantic constraint adherence, and structure-aware molecule editing.

Modern Large Language Models (LLMs) are excellent at generating synthetic data. However, their performance in sensitive domains such as text detoxification has not received proper attention from the scientific community. This paper explores the possibility of using LLM-generated synthetic toxic data as an alternative to human-generated data for training models for detoxification. Using Llama 3 and Qwen activation-patched models, we generated synthetic toxic counterparts for neutral texts from ParaDetox and SST-2 datasets. Our experiments show that models fine-tuned on synthetic data consistently perform worse than those trained on human data, with a drop in performance of up to 30% in joint metrics. The root cause is identified as a critical lexical diversity gap: LLMs generate toxic content using a small, repetitive vocabulary of insults that fails to capture the nuances and variety of human toxicity. These findings highlight the limitations of current LLMs in this domain and emphasize the continued importance of diverse, human-annotated data for building robust detoxification systems.

Large language models (LLMs) have become integral to various real-world applications, leveraging massive, web-sourced datasets like Common Crawl, C4, and FineWeb for pretraining. While these datasets provide linguistic data essential for high-quality natural language generation, they often contain harmful content, such as hate speech, misinformation, and biased narratives. Training LLMs on such unfiltered data risks perpetuating toxic behaviors, spreading misinformation, and amplifying societal biases which can undermine trust in LLM-driven applications and raise ethical concerns about their use. This paper presents a large-scale analysis of inappropriate content across these datasets, offering a comprehensive taxonomy that categorizes harmful webpages into Topical and Toxic based on their intent. We also introduce a prompt evaluation dataset, a high-accuracy Topical and Toxic Prompt (TTP), and a transformer-based model (HarmFormer) for content filtering. Additionally, we create a new multi-harm open-ended toxicity benchmark (HAVOC) and provide crucial insights into how models respond to adversarial toxic inputs. Upon publishing, we will also opensource our model signal on the entire C4 dataset. Our work offers insights into ensuring safer LLM pretraining and serves as a resource for Responsible AI (RAI) compliance.

Despite the considerable advancements in English LLMs, the progress in building comparable models for other languages has been hindered due to the scarcity of tailored resources. Our work aims to bridge this divide by introducing an expansive suite of resources specifically designed for the development of Indic LLMs, covering 22 languages, containing a total of 251B tokens and 74.8M instruction-response pairs. Recognizing the importance of both data quality and quantity, our approach combines highly curated manually verified data, unverified yet valuable data, and synthetic data. We build a clean, open-source pipeline for curating pre-training data from diverse sources, including websites, PDFs, and videos, incorporating best practices for crawling, cleaning, flagging, and deduplication. For instruction-fine tuning, we amalgamate existing Indic datasets, translate/transliterate English datasets into Indian languages, and utilize LLaMa2 and Mixtral models to create conversations grounded in articles from Indian Wikipedia and Wikihow. Additionally, we address toxicity alignment by generating toxic prompts for multiple scenarios and then generate non-toxic responses by feeding these toxic prompts to an aligned LLaMa2 model. We hope that the datasets, tools, and resources released as a part of this work will not only propel the research and development of Indic LLMs but also establish an open-source blueprint for extending such efforts to other languages. The data and other artifacts created as part of this work are released with permissive licenses.

Considerable effort has been dedicated to mitigating toxicity, but existing methods often require drastic modifications to model parameters or the use of computationally intensive auxiliary models. Furthermore, previous approaches have often neglected the crucial factor of language's evolving nature over time. In this work, we present a comprehensive perspective on toxicity mitigation that takes into account its changing nature. We introduce Goodtriever, a flexible methodology that matches the current state-of-the-art toxicity mitigation while achieving 43% relative latency reduction during inference and being more computationally efficient. By incorporating a retrieval-based approach at decoding time, Goodtriever enables toxicity-controlled text generation. Our research advocates for an increased focus on adaptable mitigation techniques, which better reflect the data drift models face when deployed in the wild. Code and data are available at https://github.com/for-ai/goodtriever.

Hate speech and toxic comments are a common concern of social media platform users. Although these comments are, fortunately, the minority in these platforms, they are still capable of causing harm. Therefore, identifying these comments is an important task for studying and preventing the proliferation of toxicity in social media. Previous work in automatically detecting toxic comments focus mainly in English, with very few work in languages like Brazilian Portuguese. In this paper, we propose a new large-scale dataset for Brazilian Portuguese with tweets annotated as either toxic or non-toxic or in different types of toxicity. We present our dataset collection and annotation process, where we aimed to select candidates covering multiple demographic groups. State-of-the-art BERT models were able to achieve 76% macro-F1 score using monolingual data in the binary case. We also show that large-scale monolingual data is still needed to create more accurate models, despite recent advances in multilingual approaches. An error analysis and experiments with multi-label classification show the difficulty of classifying certain types of toxic comments that appear less frequently in our data and highlights the need to develop models that are aware of different categories of toxicity.

Large language models (LM) generate remarkably fluent text and can be efficiently adapted across NLP tasks. Measuring and guaranteeing the quality of generated text in terms of safety is imperative for deploying LMs in the real world; to this end, prior work often relies on automatic evaluation of LM toxicity. We critically discuss this approach, evaluate several toxicity mitigation strategies with respect to both automatic and human evaluation, and analyze consequences of toxicity mitigation in terms of model bias and LM quality. We demonstrate that while basic intervention strategies can effectively optimize previously established automatic metrics on the RealToxicityPrompts dataset, this comes at the cost of reduced LM coverage for both texts about, and dialects of, marginalized groups. Additionally, we find that human raters often disagree with high automatic toxicity scores after strong toxicity reduction interventions -- highlighting further the nuances involved in careful evaluation of LM toxicity.

Perception of toxicity evolves over time and often differs between geographies and cultural backgrounds. Similarly, black-box commercially available APIs for detecting toxicity, such as the Perspective API, are not static, but frequently retrained to address any unattended weaknesses and biases. We evaluate the implications of these changes on the reproducibility of findings that compare the relative merits of models and methods that aim to curb toxicity. Our findings suggest that research that relied on inherited automatic toxicity scores to compare models and techniques may have resulted in inaccurate findings. Rescoring all models from HELM, a widely respected living benchmark, for toxicity with the recent version of the API led to a different ranking of widely used foundation models. We suggest caution in applying apples-to-apples comparisons between studies and lay recommendations for a more structured approach to evaluating toxicity over time. Code and data are available at https://github.com/for-ai/black-box-api-challenges.

In large language model (LLM) pretraining, data quality is believed to determine model quality. In this paper, we re-examine the notion of "quality" from the perspective of pre- and post-training co-design. Specifically, we explore the possibility that pre-training on more toxic data can lead to better control in post-training, ultimately decreasing a model's output toxicity. First, we use a toy experiment to study how data composition affects the geometry of features in the representation space. Next, through controlled experiments with Olmo-1B models trained on varying ratios of clean and toxic data, we find that the concept of toxicity enjoys a less entangled linear representation as the proportion of toxic data increases. Furthermore, we show that although toxic data increases the generational toxicity of the base model, it also makes the toxicity easier to remove. Evaluations on Toxigen and Real Toxicity Prompts demonstrate that models trained on toxic data achieve a better trade-off between reducing generational toxicity and preserving general capabilities when detoxifying techniques such as inference-time intervention (ITI) are applied. Our findings suggest that, with post-training taken into account, bad data may lead to good models.

Large Language Models have demonstrated impressive fluency across diverse tasks, yet their tendency to produce toxic content remains a critical challenge for AI safety and public trust. Existing toxicity mitigation approaches primarily manipulate individual neuron activations, but these methods suffer from instability, context dependence, and often compromise the model's core language abilities. To address these shortcomings, we investigate three key questions: the stability of neuron-level toxicity indicators, the advantages of structural (layer-wise) representations, and the interpretability of mechanisms driving toxic generation. Through extensive experiments on Jigsaw and ToxiCN datasets, we show that aggregated layer-wise features provide more robust signals than single neurons. Moreover, we observe conceptual limitations in prior works that conflate toxicity detection experts and generation experts within neuron-based interventions. To mitigate this, we propose a novel principled intervention technique, EigenShift, based on eigen-decomposition of the language model's final output layer. This method selectively targets generation-aligned components, enabling precise toxicity suppression without impairing linguistic competence. Our method requires no additional training or fine-tuning, incurs minimal computational cost, and is grounded in rigorous theoretical analysis.

Existing toxic detection models face significant limitations, such as lack of transparency, customization, and reproducibility. These challenges stem from the closed-source nature of their training data and the paucity of explanations for their evaluation mechanism. To address these issues, we propose a dataset creation mechanism that integrates voting and chain-of-thought processes, producing a high-quality open-source dataset for toxic content detection. Our methodology ensures diverse classification metrics for each sample and includes both classification scores and explanatory reasoning for the classifications. We utilize the dataset created through our proposed mechanism to train our model, which is then compared against existing widely-used detectors. Our approach not only enhances transparency and customizability but also facilitates better fine-tuning for specific use cases. This work contributes a robust framework for developing toxic content detection models, emphasizing openness and adaptability, thus paving the way for more effective and user-specific content moderation solutions.

Large language models (LLMs) have become integral to our professional workflows and daily lives. Nevertheless, these machine companions of ours have a critical flaw: the huge amount of data which endows them with vast and diverse knowledge, also exposes them to the inevitable toxicity and bias. While most LLMs incorporate defense mechanisms to prevent the generation of harmful content, these safeguards can be easily bypassed with minimal prompt engineering. In this paper, we introduce the new Thoroughly Engineered Toxicity (TET) dataset, comprising manually crafted prompts designed to nullify the protective layers of such models. Through extensive evaluations, we demonstrate the pivotal role of TET in providing a rigorous benchmark for evaluation of toxicity awareness in several popular LLMs: it highlights the toxicity in the LLMs that might remain hidden when using normal prompts, thus revealing subtler issues in their behavior.

As large language models become increasingly integrated into daily life, detecting implicit toxicity across diverse contexts is crucial. To this end, we introduce LifeTox, a dataset designed for identifying implicit toxicity within a broad range of advice-seeking scenarios. Unlike existing safety datasets, LifeTox comprises diverse contexts derived from personal experiences through open-ended questions. Experiments demonstrate that RoBERTa fine-tuned on LifeTox matches or surpasses the zero-shot performance of large language models in toxicity classification tasks. These results underscore the efficacy of LifeTox in addressing the complex challenges inherent in implicit toxicity.

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference--a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.

The real-world impact of polarization and toxicity in the online sphere marked the end of 2020 and the beginning of this year in a negative way. Semeval-2021, Task 5 - Toxic Spans Detection is based on a novel annotation of a subset of the Jigsaw Unintended Bias dataset and is the first language toxicity detection task dedicated to identifying the toxicity-level spans. For this task, participants had to automatically detect character spans in short comments that render the message as toxic. Our model considers applying Virtual Adversarial Training in a semi-supervised setting during the fine-tuning process of several Transformer-based models (i.e., BERT and RoBERTa), in combination with Conditional Random Fields. Our approach leads to performance improvements and more robust models, enabling us to achieve an F1-score of 65.73% in the official submission and an F1-score of 66.13% after further tuning during post-evaluation.

Existing approaches to multilingual text detoxification are hampered by the scarcity of parallel multilingual datasets. In this work, we introduce a pipeline for the generation of multilingual parallel detoxification data. We also introduce SynthDetoxM, a manually collected and synthetically generated multilingual parallel text detoxification dataset comprising 16,000 high-quality detoxification sentence pairs across German, French, Spanish and Russian. The data was sourced from different toxicity evaluation datasets and then rewritten with nine modern open-source LLMs in few-shot setting. Our experiments demonstrate that models trained on the produced synthetic datasets have superior performance to those trained on the human-annotated MultiParaDetox dataset even in data limited setting. Models trained on SynthDetoxM outperform all evaluated LLMs in few-shot setting. We release our dataset and code to help further research in multilingual text detoxification.

To date, toxicity mitigation in language models has almost entirely been focused on single-language settings. As language models embrace multilingual capabilities, it's crucial our safety measures keep pace. Recognizing this research gap, our approach expands the scope of conventional toxicity mitigation to address the complexities presented by multiple languages. In the absence of sufficient annotated datasets across languages, we employ translated data to evaluate and enhance our mitigation techniques. We also compare finetuning mitigation approaches against retrieval-augmented techniques under both static and continual toxicity mitigation scenarios. This allows us to examine the effects of translation quality and the cross-lingual transfer on toxicity mitigation. We also explore how model size and data quantity affect the success of these mitigation efforts. Covering nine languages, our study represents a broad array of linguistic families and levels of resource availability, ranging from high to mid-resource languages. Through comprehensive experiments, we provide insights into the complexities of multilingual toxicity mitigation, offering valuable insights and paving the way for future research in this increasingly important field. Code and data are available at https://github.com/for-ai/goodtriever.

Automatic toxic language detection is critical for creating safe, inclusive online spaces. However, it is a highly subjective task, with perceptions of toxic language shaped by community norms and lived experience. Existing toxicity detection models are typically trained on annotations that collapse diverse annotator perspectives into a single ground truth, erasing important context-specific notions of toxicity such as reclaimed language. To address this, we introduce MODELCITIZENS, a dataset of 6.8K social media posts and 40K toxicity annotations across diverse identity groups. To capture the role of conversational context on toxicity, typical of social media posts, we augment MODELCITIZENS posts with LLM-generated conversational scenarios. State-of-the-art toxicity detection tools (e.g. OpenAI Moderation API, GPT-o4-mini) underperform on MODELCITIZENS, with further degradation on context-augmented posts. Finally, we release LLAMACITIZEN-8B and GEMMACITIZEN-12B, LLaMA- and Gemma-based models finetuned on MODELCITIZENS, which outperform GPT-o4-mini by 5.5% on in-distribution evaluations. Our findings highlight the importance of community-informed annotation and modeling for inclusive content moderation. The data, models and code are available at https://github.com/asuvarna31/modelcitizens.

Pretrained neural language models (LMs) are prone to generating racist, sexist, or otherwise toxic language which hinders their safe deployment. We investigate the extent to which pretrained LMs can be prompted to generate toxic language, and the effectiveness of controllable text generation algorithms at preventing such toxic degeneration. We create and release RealToxicityPrompts, a dataset of 100K naturally occurring, sentence-level prompts derived from a large corpus of English web text, paired with toxicity scores from a widely-used toxicity classifier. Using RealToxicityPrompts, we find that pretrained LMs can degenerate into toxic text even from seemingly innocuous prompts. We empirically assess several controllable generation methods, and find that while data- or compute-intensive methods (e.g., adaptive pretraining on non-toxic data) are more effective at steering away from toxicity than simpler solutions (e.g., banning "bad" words), no current method is failsafe against neural toxic degeneration. To pinpoint the potential cause of such persistent toxic degeneration, we analyze two web text corpora used to pretrain several LMs (including GPT-2; Radford et. al, 2019), and find a significant amount of offensive, factually unreliable, and otherwise toxic content. Our work provides a test bed for evaluating toxic generations by LMs and stresses the need for better data selection processes for pretraining.

Researchers and developers increasingly rely on toxicity scoring to moderate generative language model outputs, in settings such as customer service, information retrieval, and content generation. However, toxicity scoring may render pertinent information inaccessible, rigidify or "value-lock" cultural norms, and prevent language reclamation processes, particularly for marginalized people. In this work, we extend the concept of algorithmic recourse to generative language models: we provide users a novel mechanism to achieve their desired prediction by dynamically setting thresholds for toxicity filtering. Users thereby exercise increased agency relative to interactions with the baseline system. A pilot study (n = 30) supports the potential of our proposed recourse mechanism, indicating improvements in usability compared to fixed-threshold toxicity-filtering of model outputs. Future work should explore the intersection of toxicity scoring, model controllability, user agency, and language reclamation processes -- particularly with regard to the bias that many communities encounter when interacting with generative language models.

Traditional toxicity detection models have focused on the single utterance level without deeper understanding of context. We introduce CONDA, a new dataset for in-game toxic language detection enabling joint intent classification and slot filling analysis, which is the core task of Natural Language Understanding (NLU). The dataset consists of 45K utterances from 12K conversations from the chat logs of 1.9K completed Dota 2 matches. We propose a robust dual semantic-level toxicity framework, which handles utterance and token-level patterns, and rich contextual chatting history. Accompanying the dataset is a thorough in-game toxicity analysis, which provides comprehensive understanding of context at utterance, token, and dual levels. Inspired by NLU, we also apply its metrics to the toxicity detection tasks for assessing toxicity and game-specific aspects. We evaluate strong NLU models on CONDA, providing fine-grained results for different intent classes and slot classes. Furthermore, we examine the coverage of toxicity nature in our dataset by comparing it with other toxicity datasets.

Adverse drug events (ADEs) significantly impact clinical research, causing many clinical trial failures. ADE prediction is key for developing safer medications and enhancing patient outcomes. To support this effort, we introduce CT-ADE, a dataset for multilabel predictive modeling of ADEs in monopharmacy treatments. CT-ADE integrates data from 2,497 unique drugs, encompassing 168,984 drug-ADE pairs extracted from clinical trials, annotated with patient and contextual information, and comprehensive ADE concepts standardized across multiple levels of the MedDRA ontology. Preliminary analyses with large language models (LLMs) achieved F1-scores up to 55.90%. Models using patient and contextual information showed F1-score improvements of 21%-38% over models using only chemical structure data. Our results highlight the importance of target population and treatment regimens in the predictive modeling of ADEs, offering greater performance gains than LLM domain specialization and scaling. CT-ADE provides an essential tool for researchers aiming to leverage artificial intelligence and machine learning to enhance patient safety and minimize the impact of ADEs on pharmaceutical research and development. The dataset is publicly accessible at https://github.com/ds4dh/CT-ADE.

The open-endedness of large language models (LLMs) combined with their impressive capabilities may lead to new safety issues when being exploited for malicious use. While recent studies primarily focus on probing toxic outputs that can be easily detected with existing toxicity classifiers, we show that LLMs can generate diverse implicit toxic outputs that are exceptionally difficult to detect via simply zero-shot prompting. Moreover, we propose a reinforcement learning (RL) based attacking method to further induce the implicit toxicity in LLMs. Specifically, we optimize the language model with a reward that prefers implicit toxic outputs to explicit toxic and non-toxic ones. Experiments on five widely-adopted toxicity classifiers demonstrate that the attack success rate can be significantly improved through RL fine-tuning. For instance, the RL-finetuned LLaMA-13B model achieves an attack success rate of 90.04% on BAD and 62.85% on Davinci003. Our findings suggest that LLMs pose a significant threat in generating undetectable implicit toxic outputs. We further show that fine-tuning toxicity classifiers on the annotated examples from our attacking method can effectively enhance their ability to detect LLM-generated implicit toxic language. The code is publicly available at https://github.com/thu-coai/Implicit-Toxicity.

Despite remarkable advances that large language models have achieved in chatbots, maintaining a non-toxic user-AI interactive environment has become increasingly critical nowadays. However, previous efforts in toxicity detection have been mostly based on benchmarks derived from social media content, leaving the unique challenges inherent to real-world user-AI interactions insufficiently explored. In this work, we introduce ToxicChat, a novel benchmark based on real user queries from an open-source chatbot. This benchmark contains the rich, nuanced phenomena that can be tricky for current toxicity detection models to identify, revealing a significant domain difference compared to social media content. Our systematic evaluation of models trained on existing toxicity datasets has shown their shortcomings when applied to this unique domain of ToxicChat. Our work illuminates the potentially overlooked challenges of toxicity detection in real-world user-AI conversations. In the future, ToxicChat can be a valuable resource to drive further advancements toward building a safe and healthy environment for user-AI interactions.

Toxic conversations during software development interactions may have serious repercussions on a Free and Open Source Software (FOSS) development project. For example, victims of toxic conversations may become afraid to express themselves, therefore get demotivated, and may eventually leave the project. Automated filtering of toxic conversations may help a FOSS community to maintain healthy interactions among its members. However, off-the-shelf toxicity detectors perform poorly on Software Engineering (SE) datasets, such as one curated from code review comments. To encounter this challenge, we present ToxiCR, a supervised learning-based toxicity identification tool for code review interactions. ToxiCR includes a choice to select one of the ten supervised learning algorithms, an option to select text vectorization techniques, eight preprocessing steps, and a large-scale labeled dataset of 19,571 code review comments. Two out of those eight preprocessing steps are SE domain specific. With our rigorous evaluation of the models with various combinations of preprocessing steps and vectorization techniques, we have identified the best combination for our dataset that boosts 95.8% accuracy and 88.9% F1 score. ToxiCR significantly outperforms existing toxicity detectors on our dataset. We have released our dataset, pre-trained models, evaluation results, and source code publicly available at: https://github.com/WSU-SEAL/ToxiCR

Prior works on detoxification are scattered in the sense that they do not cover all aspects of detoxification needed in a real-world scenario. Notably, prior works restrict the task of developing detoxification models to only a seen subset of platforms, leaving the question of how the models would perform on unseen platforms unexplored. Additionally, these works do not address non-detoxifiability, a phenomenon whereby the toxic text cannot be detoxified without altering the meaning. We propose GreenLLaMA, the first comprehensive end-to-end detoxification framework, which attempts to alleviate the aforementioned limitations. We first introduce a cross-platform pseudo-parallel corpus applying multi-step data processing and generation strategies leveraging ChatGPT. We then train a suite of detoxification models with our cross-platform corpus. We show that our detoxification models outperform the SoTA model trained with human-annotated parallel corpus. We further introduce explanation to promote transparency and trustworthiness. GreenLLaMA additionally offers a unique paraphrase detector especially dedicated for the detoxification task to tackle the non-detoxifiable cases. Through experimental analysis, we demonstrate the effectiveness of our cross-platform corpus and the robustness of GreenLLaMA against adversarial toxicity.

Large language models (LLMs) and small language models (SLMs) are being adopted at remarkable speed, although their safety still remains a serious concern. With the advent of multilingual S/LLMs, the question now becomes a matter of scale: can we expand multilingual safety evaluations of these models with the same velocity at which they are deployed? To this end we introduce RTP-LX, a human-transcreated and human-annotated corpus of toxic prompts and outputs in 28 languages. RTP-LX follows participatory design practices, and a portion of the corpus is especially designed to detect culturally-specific toxic language. We evaluate seven S/LLMs on their ability to detect toxic content in a culturally-sensitive, multilingual scenario. We find that, although they typically score acceptably in terms of accuracy, they have low agreement with human judges when judging holistically the toxicity of a prompt, and have difficulty discerning harm in context-dependent scenarios, particularly with subtle-yet-harmful content (e.g. microagressions, bias). We release of this dataset to contribute to further reduce harmful uses of these models and improve their safe deployment.

Machine learning models are often used to inform real world risk assessment tasks: predicting consumer default risk, predicting whether a person suffers from a serious illness, or predicting a person's risk to appear in court. Given multiple models that perform almost equally well for a prediction task, to what extent do predictions vary across these models? If predictions are relatively consistent for similar models, then the standard approach of choosing the model that optimizes a penalized loss suffices. But what if predictions vary significantly for similar models? In machine learning, this is referred to as predictive multiplicity i.e. the prevalence of conflicting predictions assigned by near-optimal competing models. In this paper, we present a framework for measuring predictive multiplicity in probabilistic classification (predicting the probability of a positive outcome). We introduce measures that capture the variation in risk estimates over the set of competing models, and develop optimization-based methods to compute these measures efficiently and reliably for convex empirical risk minimization problems. We demonstrate the incidence and prevalence of predictive multiplicity in real-world tasks. Further, we provide insight into how predictive multiplicity arises by analyzing the relationship between predictive multiplicity and data set characteristics (outliers, separability, and majority-minority structure). Our results emphasize the need to report predictive multiplicity more widely.

Recent alignment algorithms such as direct preference optimization (DPO) have been developed to improve the safety of large language models (LLMs) by training these models to match human behaviors exemplified by preference data. However, these methods are both computationally intensive and lacking in controllability and transparency, making them prone to jailbreaking and inhibiting their widespread use. Furthermore, these tuning-based methods require large-scale preference data for training and are susceptible to noisy preference data. In this paper, we introduce a tuning-free alignment alternative (DeTox) and demonstrate its effectiveness under the use case of toxicity reduction. Grounded on theory from factor analysis, DeTox is a sample-efficient model editing approach that identifies a toxic subspace in the model parameter space and reduces model toxicity by projecting away the detected subspace. The toxic sub-space is identified by extracting preference data embeddings from the language model, and removing non-toxic information from these embeddings. We show that DeTox is more sample-efficient than DPO, further showcasing greater robustness to noisy data. Finally, we establish both theoretical and empirical connections between DeTox and DPO, showing that DeTox can be interpreted as a denoised version of a single DPO step.

Predicting multiple heterogeneous biological and medical targets is a challenge for traditional deep learning models. In contrast to single-task learning, in which a separate model is trained for each target, multi-task learning (MTL) optimizes a single model to predict multiple related targets simultaneously. To address this challenge, we propose the Multi-gate Mixture-of-Experts with Exclusivity (MMoEEx). Our work aims to tackle the heterogeneous MTL setting, in which the same model optimizes multiple tasks with different characteristics. Such a scenario can overwhelm current MTL approaches due to the challenges in balancing shared and task-specific representations and the need to optimize tasks with competing optimization paths. Our method makes two key contributions: first, we introduce an approach to induce more diversity among experts, thus creating representations more suitable for highly imbalanced and heterogenous MTL learning; second, we adopt a two-step optimization [6, 11] approach to balancing the tasks at the gradient level. We validate our method on three MTL benchmark datasets, including Medical Information Mart for Intensive Care (MIMIC-III) and PubChem BioAssay (PCBA).

Large Language Models (LLMs) have demonstrated remarkable capabilities in generating human-like text, but their output may not be aligned with the user or even produce harmful content. This paper presents a novel approach to detect and steer concepts such as toxicity before generation. We introduce the Sparse Conditioned Autoencoder (SCAR), a single trained module that extends the otherwise untouched LLM. SCAR ensures full steerability, towards and away from concepts (e.g., toxic content), without compromising the quality of the model's text generation on standard evaluation benchmarks. We demonstrate the effective application of our approach through a variety of concepts, including toxicity, safety, and writing style alignment. As such, this work establishes a robust framework for controlling LLM generations, ensuring their ethical and safe deployment in real-world applications.

Open-source large language models are becoming increasingly available and popular among researchers and practitioners. While significant progress has been made on open-weight models, open training data is a practice yet to be adopted by the leading open-weight models creators. At the same time, there researchers are working to make language models safer. We propose a data curation pipeline to reduce harmful outputs by models trained on public domain data. There are unique challenges to working with public domain data, as these sources differ from web text in both form and content. Many sources are historical documents and are the result of Optical Character Recognition (OCR). Consequently, current state-of-the-art approaches to toxicity filtering are often infeasible or inappropriate for open data models. In this paper, we introduce a new fully open-source pipeline for open-data toxicity filtering. Our contributions are threefold. We create a custom training dataset, ToxicCommons, which is composed of texts which have been classified across five different dimensions (racial/origin-based, gender/sex-based, religious, ability-based discrimination, and violence). We use this dataset to train a custom classifier, Celadon, that can be used to detect toxic content in open data more efficiently at a larger scale. Finally, we describe the balanced approach to content filtration that optimizes safety filtering with respect to the filtered data available for training.

Polarization is defined as divisive opinions held by two or more groups on substantive issues. As the world's third-largest democracy, Indonesia faces growing concerns about the interplay between political polarization and online toxicity, which is often directed at vulnerable minority groups. Despite the importance of this issue, previous NLP research has not fully explored the relationship between toxicity and polarization. To bridge this gap, we present a novel multi-label Indonesian dataset that incorporates toxicity, polarization, and annotator demographic information. Benchmarking this dataset using BERT-base models and large language models (LLMs) shows that polarization information enhances toxicity classification, and vice versa. Furthermore, providing demographic information significantly improves the performance of polarization classification.

This paper presents Tiny-toxic-detector, a compact transformer-based model designed for toxic content detection. Despite having only 2.1 million parameters, Tiny-toxic-detector achieves competitive performance on benchmark datasets, with 90.97% accuracy on ToxiGen and 86.98% accuracy on the Jigsaw dataset, rivaling models over 50 times its size. This efficiency enables deployment in resource-constrained environments, addressing the need for effective content moderation tools that balance performance with computational efficiency. The model architecture features 4 transformer encoder layers, each with 2 attention heads, an embedding dimension of 64, and a feedforward dimension of 128. Trained on both public and private datasets, Tiny-toxic-detector demonstrates the potential of efficient, task-specific models for addressing online toxicity. The paper covers the model architecture, training process, performance benchmarks, and limitations, underscoring its suitability for applications such as social media monitoring and content moderation. By achieving results comparable to much larger models while significantly reducing computational demands, Tiny-toxic-detector represents progress toward more sustainable and scalable AI-driven content moderation solutions.

In recent years, the widespread use of social media has led to an increase in the generation of toxic and offensive content on online platforms. In response, social media platforms have worked on developing automatic detection methods and employing human moderators to cope with this deluge of offensive content. While various state-of-the-art statistical models have been applied to detect toxic posts, there are only a few studies that focus on detecting the words or expressions that make a post offensive. This motivates the organization of the SemEval-2021 Task 5: Toxic Spans Detection competition, which has provided participants with a dataset containing toxic spans annotation in English posts. In this paper, we present the WLV-RIT entry for the SemEval-2021 Task 5. Our best performing neural transformer model achieves an 0.68 F1-Score. Furthermore, we develop an open-source framework for multilingual detection of offensive spans, i.e., MUDES, based on neural transformers that detect toxic spans in texts.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

Air pollution remains a leading global health risk, exacerbated by rapid industrialization and urbanization, contributing significantly to morbidity and mortality rates. In this paper, we introduce AirCast, a novel multi-variable air pollution forecasting model, by combining weather and air quality variables. AirCast employs a multi-task head architecture that simultaneously forecasts atmospheric conditions and pollutant concentrations, improving its understanding of how weather patterns affect air quality. Predicting extreme pollution events is challenging due to their rare occurrence in historic data, resulting in a heavy-tailed distribution of pollution levels. To address this, we propose a novel Frequency-weighted Mean Absolute Error (fMAE) loss, adapted from the class-balanced loss for regression tasks. Informed from domain knowledge, we investigate the selection of key variables known to influence pollution levels. Additionally, we align existing weather and chemical datasets across spatial and temporal dimensions. AirCast's integrated approach, combining multi-task learning, frequency weighted loss and domain informed variable selection, enables more accurate pollution forecasts. Our source code and models are made public here (https://github.com/vishalned/AirCast.git)

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

Activity and property prediction models are the central workhorses in drug discovery and materials sciences, but currently they have to be trained or fine-tuned for new tasks. Without training or fine-tuning, scientific language models could be used for such low-data tasks through their announced zero- and few-shot capabilities. However, their predictive quality at activity prediction is lacking. In this work, we envision a novel type of activity prediction model that is able to adapt to new prediction tasks at inference time, via understanding textual information describing the task. To this end, we propose a new architecture with separate modules for chemical and natural language inputs, and a contrastive pre-training objective on data from large biochemical databases. In extensive experiments, we show that our method CLAMP yields improved predictive performance on few-shot learning benchmarks and zero-shot problems in drug discovery. We attribute the advances of our method to the modularized architecture and to our pre-training objective.

Detoxifying offensive language while preserving the speaker's original intent is a challenging yet critical goal for improving the quality of online interactions. Although large language models (LLMs) show promise in rewriting toxic content, they often default to overly polite rewrites, distorting the emotional tone and communicative intent. This problem is especially acute in Chinese, where toxicity often arises implicitly through emojis, homophones, or discourse context. We present ToxiRewriteCN, the first Chinese detoxification dataset explicitly designed to preserve sentiment polarity. The dataset comprises 1,556 carefully annotated triplets, each containing a toxic sentence, a sentiment-aligned non-toxic rewrite, and labeled toxic spans. It covers five real-world scenarios: standard expressions, emoji-induced and homophonic toxicity, as well as single-turn and multi-turn dialogues. We evaluate 17 LLMs, including commercial and open-source models with variant architectures, across four dimensions: detoxification accuracy, fluency, content preservation, and sentiment polarity. Results show that while commercial and MoE models perform best overall, all models struggle to balance safety with emotional fidelity in more subtle or context-heavy settings such as emoji, homophone, and dialogue-based inputs. We release ToxiRewriteCN to support future research on controllable, sentiment-aware detoxification for Chinese.

Added toxicity in the context of translation refers to the fact of producing a translation output with more toxicity than there exists in the input. In this paper, we present MinTox which is a novel pipeline to identify added toxicity and mitigate this issue which works at inference time. MinTox uses a toxicity detection classifier which is multimodal (speech and text) and works in languages at scale. The mitigation method is applied to languages at scale and directly in text outputs. MinTox is applied to SEAMLESSM4T, which is the latest multimodal and massively multilingual machine translation system. For this system, MinTox achieves significant added toxicity mitigation across domains, modalities and language directions. MinTox manages to approximately filter out from 25% to 95% of added toxicity (depending on the modality and domain) while keeping translation quality.

While alignment algorithms are now commonly used to tune pre-trained language models towards a user's preferences, we lack explanations for the underlying mechanisms in which models become ``aligned'', thus making it difficult to explain phenomena like jailbreaks. In this work we study a popular algorithm, direct preference optimization (DPO), and the mechanisms by which it reduces toxicity. Namely, we first study how toxicity is represented and elicited in a pre-trained language model, GPT2-medium. We then apply DPO with a carefully crafted pairwise dataset to reduce toxicity. We examine how the resulting model averts toxic outputs, and find that capabilities learned from pre-training are not removed, but rather bypassed. We use this insight to demonstrate a simple method to un-align the model, reverting it back to its toxic behavior.

Foundation models have been transformational in machine learning fields such as natural language processing and computer vision. Similar success in atomic property prediction has been limited due to the challenges of training effective models across multiple chemical domains. To address this, we introduce Joint Multi-domain Pre-training (JMP), a supervised pre-training strategy that simultaneously trains on multiple datasets from different chemical domains, treating each dataset as a unique pre-training task within a multi-task framework. Our combined training dataset consists of sim120M systems from OC20, OC22, ANI-1x, and Transition-1x. We evaluate performance and generalization by fine-tuning over a diverse set of downstream tasks and datasets including: QM9, rMD17, MatBench, QMOF, SPICE, and MD22. JMP demonstrates an average improvement of 59% over training from scratch, and matches or sets state-of-the-art on 34 out of 40 tasks. Our work highlights the potential of pre-training strategies that utilize diverse data to advance property prediction across chemical domains, especially for low-data tasks.

Text detoxification has the potential to mitigate the harms of toxicity by rephrasing text to remove offensive meaning, but subtle toxicity remains challenging to tackle. We introduce MaRCo, a detoxification algorithm that combines controllable generation and text rewriting methods using a Product of Experts with autoencoder language models (LMs). MaRCo uses likelihoods under a non-toxic LM (expert) and a toxic LM (anti-expert) to find candidate words to mask and potentially replace. We evaluate our method on several subtle toxicity and microaggressions datasets, and show that it not only outperforms baselines on automatic metrics, but MaRCo's rewrites are preferred 2.1 times more in human evaluation. Its applicability to instances of subtle toxicity is especially promising, demonstrating a path forward for addressing increasingly elusive online hate.

Generic `toxicity' classifiers continue to be used for evaluating the potential for harm in natural language generation, despite mounting evidence of their shortcomings. We consider the challenge of measuring misogyny in natural language generation, and argue that generic `toxicity' classifiers are inadequate for this task. We use data from two well-characterised `Incel' communities on Reddit that differ primarily in their degrees of misogyny to construct a pair of training corpora which we use to fine-tune two language models. We show that an open source `toxicity' classifier is unable to distinguish meaningfully between generations from these models. We contrast this with a misogyny-specific lexicon recently proposed by feminist subject-matter experts, demonstrating that, despite the limitations of simple lexicon-based approaches, this shows promise as a benchmark to evaluate language models for misogyny, and that it is sensitive enough to reveal the known differences in these Reddit communities. Our preliminary findings highlight the limitations of a generic approach to evaluating harms, and further emphasise the need for careful benchmark design and selection in natural language evaluation.

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

In the era of Large Language Models (LLMs), given their remarkable text understanding and generation abilities, there is an unprecedented opportunity to develop new, LLM-based methods for trustworthy medical knowledge synthesis, extraction and summarization. This paper focuses on the problem of Pharmacovigilance (PhV), where the significance and challenges lie in identifying Adverse Drug Events (ADEs) from diverse text sources, such as medical literature, clinical notes, and drug labels. Unfortunately, this task is hindered by factors including variations in the terminologies of drugs and outcomes, and ADE descriptions often being buried in large amounts of narrative text. We present MALADE, the first effective collaborative multi-agent system powered by LLM with Retrieval Augmented Generation for ADE extraction from drug label data. This technique involves augmenting a query to an LLM with relevant information extracted from text resources, and instructing the LLM to compose a response consistent with the augmented data. MALADE is a general LLM-agnostic architecture, and its unique capabilities are: (1) leveraging a variety of external sources, such as medical literature, drug labels, and FDA tools (e.g., OpenFDA drug information API), (2) extracting drug-outcome association in a structured format along with the strength of the association, and (3) providing explanations for established associations. Instantiated with GPT-4 Turbo or GPT-4o, and FDA drug label data, MALADE demonstrates its efficacy with an Area Under ROC Curve of 0.90 against the OMOP Ground Truth table of ADEs. Our implementation leverages the Langroid multi-agent LLM framework and can be found at https://github.com/jihyechoi77/malade.

Accumulated clinical studies show that microbes living in humans interact closely with human hosts, and get involved in modulating drug efficacy and drug toxicity. Microbes have become novel targets for the development of antibacterial agents. Therefore, screening of microbe-drug associations can benefit greatly drug research and development. With the increase of microbial genomic and pharmacological datasets, we are greatly motivated to develop an effective computational method to identify new microbe-drug associations. In this paper, we proposed a novel method, Graph2MDA, to predict microbe-drug associations by using variational graph autoencoder (VGAE). We constructed multi-modal attributed graphs based on multiple features of microbes and drugs, such as molecular structures, microbe genetic sequences, and function annotations. Taking as input the multi-modal attribute graphs, VGAE was trained to learn the informative and interpretable latent representations of each node and the whole graph, and then a deep neural network classifier was used to predict microbe-drug associations. The hyperparameter analysis and model ablation studies showed the sensitivity and robustness of our model. We evaluated our method on three independent datasets and the experimental results showed that our proposed method outperformed six existing state-of-the-art methods. We also explored the meaningness of the learned latent representations of drugs and found that the drugs show obvious clustering patterns that are significantly consistent with drug ATC classification. Moreover, we conducted case studies on two microbes and two drugs and found 75\%-95\% predicted associations have been reported in PubMed literature. Our extensive performance evaluations validated the effectiveness of our proposed method.\

In line with recent advances in neural drug design and sensitivity prediction, we propose a novel architecture for interpretable prediction of anticancer compound sensitivity using a multimodal attention-based convolutional encoder. Our model is based on the three key pillars of drug sensitivity: compounds' structure in the form of a SMILES sequence, gene expression profiles of tumors and prior knowledge on intracellular interactions from protein-protein interaction networks. We demonstrate that our multiscale convolutional attention-based (MCA) encoder significantly outperforms a baseline model trained on Morgan fingerprints, a selection of encoders based on SMILES as well as previously reported state of the art for multimodal drug sensitivity prediction (R2 = 0.86 and RMSE = 0.89). Moreover, the explainability of our approach is demonstrated by a thorough analysis of the attention weights. We show that the attended genes significantly enrich apoptotic processes and that the drug attention is strongly correlated with a standard chemical structure similarity index. Finally, we report a case study of two receptor tyrosine kinase (RTK) inhibitors acting on a leukemia cell line, showcasing the ability of the model to focus on informative genes and submolecular regions of the two compounds. The demonstrated generalizability and the interpretability of our model testify its potential for in-silico prediction of anticancer compound efficacy on unseen cancer cells, positioning it as a valid solution for the development of personalized therapies as well as for the evaluation of candidate compounds in de novo drug design.

Large language models (LLMs) like ChatGPT and Gemini have significantly advanced natural language processing, enabling various applications such as chatbots and automated content generation. However, these models can be exploited by malicious individuals who craft toxic prompts to elicit harmful or unethical responses. These individuals often employ jailbreaking techniques to bypass safety mechanisms, highlighting the need for robust toxic prompt detection methods. Existing detection techniques, both blackbox and whitebox, face challenges related to the diversity of toxic prompts, scalability, and computational efficiency. In response, we propose ToxicDetector, a lightweight greybox method designed to efficiently detect toxic prompts in LLMs. ToxicDetector leverages LLMs to create toxic concept prompts, uses embedding vectors to form feature vectors, and employs a Multi-Layer Perceptron (MLP) classifier for prompt classification. Our evaluation on various versions of the LLama models, Gemma-2, and multiple datasets demonstrates that ToxicDetector achieves a high accuracy of 96.39\% and a low false positive rate of 2.00\%, outperforming state-of-the-art methods. Additionally, ToxicDetector's processing time of 0.0780 seconds per prompt makes it highly suitable for real-time applications. ToxicDetector achieves high accuracy, efficiency, and scalability, making it a practical method for toxic prompt detection in LLMs.

With the fast development of COVID-19 into a global pandemic, scientists around the globe are desperately searching for effective antiviral therapeutic agents. Bridging systems biology and drug discovery, we propose a deep learning framework for conditional de novo design of antiviral candidate drugs tailored against given protein targets. First, we train a multimodal ligand--protein binding affinity model on predicting affinities of antiviral compounds to target proteins and couple this model with pharmacological toxicity predictors. Exploiting this multi-objective as a reward function of a conditional molecular generator (consisting of two VAEs), we showcase a framework that navigates the chemical space toward regions with more antiviral molecules. Specifically, we explore a challenging setting of generating ligands against unseen protein targets by performing a leave-one-out-cross-validation on 41 SARS-CoV-2-related target proteins. Using deep RL, it is demonstrated that in 35 out of 41 cases, the generation is biased towards sampling more binding ligands, with an average increase of 83% comparing to an unbiased VAE. We present a case-study on a potential Envelope-protein inhibitor and perform a synthetic accessibility assessment of the best generated molecules is performed that resembles a viable roadmap towards a rapid in-vitro evaluation of potential SARS-CoV-2 inhibitors.

The primary goal of drug safety researchers and regulators is to promptly identify adverse drug reactions. Doing so may in turn prevent or reduce the harm to patients and ultimately improve public health. Evaluating and monitoring drug safety (i.e., pharmacovigilance) involves analyzing an ever growing collection of spontaneous reports from health professionals, physicians, and pharmacists, and information voluntarily submitted by patients. In this scenario, facilitating analysis of such reports via automation has the potential to rapidly identify safety signals. Unfortunately, public resources for developing natural language models for this task are scant. We present PHEE, a novel dataset for pharmacovigilance comprising over 5000 annotated events from medical case reports and biomedical literature, making it the largest such public dataset to date. We describe the hierarchical event schema designed to provide coarse and fine-grained information about patients' demographics, treatments and (side) effects. Along with the discussion of the dataset, we present a thorough experimental evaluation of current state-of-the-art approaches for biomedical event extraction, point out their limitations, and highlight open challenges to foster future research in this area.

The recent advances in neural language models have also been successfully applied to the field of chemistry, offering generative solutions for classical problems in molecular design and synthesis planning. These new methods have the potential to optimize laboratory operations and fuel a new era of data-driven automation in scientific discovery. However, specialized models are still typically required for each task, leading to the need for problem-specific fine-tuning and neglecting task interrelations. The main obstacle in this field is the lack of a unified representation between natural language and chemical representations, complicating and limiting human-machine interaction. Here, we propose a multi-domain, multi-task language model to solve a wide range of tasks in both the chemical and natural language domains. By leveraging multi-task learning, our model can handle chemical and natural language concurrently, without requiring expensive pre-training on single domains or task-specific models. Interestingly, sharing weights across domains remarkably improves our model when benchmarked against state-of-the-art baselines on single-domain and cross-domain tasks. In particular, sharing information across domains and tasks gives rise to large improvements in cross-domain tasks, the magnitude of which increase with scale, as measured by more than a dozen of relevant metrics. Our work suggests that such models can robustly and efficiently accelerate discovery in physical sciences by superseding problem-specific fine-tuning and enhancing human-model interactions.

Peptides are essential in biological processes and therapeutics. In this study, we introduce Multi-Peptide, an innovative approach that combines transformer-based language models with Graph Neural Networks (GNNs) to predict peptide properties. We combine PeptideBERT, a transformer model tailored for peptide property prediction, with a GNN encoder to capture both sequence-based and structural features. By employing Contrastive Language-Image Pre-training (CLIP), Multi-Peptide aligns embeddings from both modalities into a shared latent space, thereby enhancing the model's predictive accuracy. Evaluations on hemolysis and nonfouling datasets demonstrate Multi-Peptide's robustness, achieving state-of-the-art 86.185% accuracy in hemolysis prediction. This study highlights the potential of multimodal learning in bioinformatics, paving the way for accurate and reliable predictions in peptide-based research and applications.

Pre-trained language models (LMs) are shown to easily generate toxic language. In this work, we systematically explore domain-adaptive training to reduce the toxicity of language models. We conduct this study on three dimensions: training corpus, model size, and parameter efficiency. For the training corpus, we propose to leverage the generative power of LMs and generate nontoxic datasets for domain-adaptive training, which mitigates the exposure bias and is shown to be more data-efficient than using a curated pre-training corpus. We demonstrate that the self-generation method consistently outperforms the existing baselines across various model sizes on both automatic and human evaluations, even when it uses a 1/3 smaller training corpus. We then comprehensively study detoxifying LMs with parameter sizes ranging from 126M up to 530B (3x larger than GPT-3), a scale that has never been studied before. We find that i) large LMs have similar toxicity levels as smaller ones given the same pre-training corpus, and ii) large LMs require more endeavor to detoxify. We also explore parameter-efficient training methods for detoxification. We demonstrate that adding and training adapter-only layers in LMs not only saves a lot of parameters but also achieves a better trade-off between toxicity and perplexity than whole model adaptation for the large-scale models.

Biased associations have been a challenge in the development of classifiers for detecting toxic language, hindering both fairness and accuracy. As potential solutions, we investigate recently introduced debiasing methods for text classification datasets and models, as applied to toxic language detection. Our focus is on lexical (e.g., swear words, slurs, identity mentions) and dialectal markers (specifically African American English). Our comprehensive experiments establish that existing methods are limited in their ability to prevent biased behavior in current toxicity detectors. We then propose an automatic, dialect-aware data correction method, as a proof-of-concept. Despite the use of synthetic labels, this method reduces dialectal associations with toxicity. Overall, our findings show that debiasing a model trained on biased toxic language data is not as effective as simply relabeling the data to remove existing biases.

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through integration of all available multi-omics data is an under-study research direction. Here, we present SeNMo (Self-normalizing Network for Multi-omics), a deep neural network trained on multi-omics data across 33 cancer types. SeNMo is efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for the task of overall survival using pan-cancer data involving 33 cancer sites from Genomics Data Commons (GDC). The training data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. We evaluated the model's performance in predicting overall survival using concordance index (C-Index). SeNMo performed consistently well in training regime, with the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo proved to be a mini-foundation model for multi-omics oncology data because it demonstrated robust performance, and adaptability not only across molecular data types but also on the classification task of predicting the primary cancer type of patients. SeNMo can be further scaled to any cancer site and molecular data type. We believe SeNMo and similar models are poised to transform the oncology landscape, offering hope for more effective, efficient, and patient-centric cancer care.

The mining of adverse drug events (ADEs) is pivotal in pharmacovigilance, enhancing patient safety by identifying potential risks associated with medications, facilitating early detection of adverse events, and guiding regulatory decision-making. Traditional ADE detection methods are reliable but slow, not easily adaptable to large-scale operations, and offer limited information. With the exponential increase in data sources like social media content, biomedical literature, and Electronic Medical Records (EMR), extracting relevant ADE-related information from these unstructured texts is imperative. Previous ADE mining studies have focused on text-based methodologies, overlooking visual cues, limiting contextual comprehension, and hindering accurate interpretation. To address this gap, we present a MultiModal Adverse Drug Event (MMADE) detection dataset, merging ADE-related textual information with visual aids. Additionally, we introduce a framework that leverages the capabilities of LLMs and VLMs for ADE detection by generating detailed descriptions of medical images depicting ADEs, aiding healthcare professionals in visually identifying adverse events. Using our MMADE dataset, we showcase the significance of integrating visual cues from images to enhance overall performance. This approach holds promise for patient safety, ADE awareness, and healthcare accessibility, paving the way for further exploration in personalized healthcare.

Despite extensive research on toxic speech detection in text, a critical gap remains in handling spoken Mandarin audio. The lack of annotated datasets that capture the unique prosodic cues and culturally specific expressions in Mandarin leaves spoken toxicity underexplored. To address this, we introduce ToxicTone -- the largest public dataset of its kind -- featuring detailed annotations that distinguish both forms of toxicity (e.g., profanity, bullying) and sources of toxicity (e.g., anger, sarcasm, dismissiveness). Our data, sourced from diverse real-world audio and organized into 13 topical categories, mirrors authentic communication scenarios. We also propose a multimodal detection framework that integrates acoustic, linguistic, and emotional features using state-of-the-art speech and emotion encoders. Extensive experiments show our approach outperforms text-only and baseline models, underscoring the essential role of speech-specific cues in revealing hidden toxic expressions.

Millions of individuals' well-being are challenged by the harms of substance use. Harm reduction as a public health strategy is designed to improve their health outcomes and reduce safety risks. Some large language models (LLMs) have demonstrated a decent level of medical knowledge, promising to address the information needs of people who use drugs (PWUD). However, their performance in relevant tasks remains largely unexplored. We introduce HRIPBench, a benchmark designed to evaluate LLM's accuracy and safety risks in harm reduction information provision. The benchmark dataset HRIP-Basic has 2,160 question-answer-evidence pairs. The scope covers three tasks: checking safety boundaries, providing quantitative values, and inferring polysubstance use risks. We build the Instruction and RAG schemes to evaluate model behaviours based on their inherent knowledge and the integration of domain knowledge. Our results indicate that state-of-the-art LLMs still struggle to provide accurate harm reduction information, and sometimes, carry out severe safety risks to PWUD. The use of LLMs in harm reduction contexts should be cautiously constrained to avoid inducing negative health outcomes. WARNING: This paper contains illicit content that potentially induces harms.

Large Language Models (LLMs) have demonstrated great potential as generalist assistants, showcasing powerful task understanding and problem-solving capabilities. To deploy LLMs as AI assistants, it is crucial that these models exhibit desirable behavioral traits, such as non-toxicity and resilience against jailbreak attempts. Current methods for detoxification or preventing jailbreaking usually involve Supervised Fine-Tuning (SFT) or Reinforcement Learning from Human Feedback (RLHF), which requires finetuning billions of parameters through gradient descent with substantial computation cost. Furthermore, models modified through SFT and RLHF may deviate from the pretrained models, potentially leading to a degradation in foundational LLM capabilities. In this paper, we observe that surprisingly, directly editing a small subset of parameters can effectively modulate specific behaviors of LLMs, such as detoxification and resistance to jailbreaking. Specifically, for a behavior that we aim to avoid, we employ a linear classifier, which we term the behavior probe, to classify binary behavior labels within the hidden state space of the LLM. Using this probe, we introduce an algorithm to identify a critical subset of LLM parameters that significantly influence this targeted behavior. Then we directly edit these selected parameters by shifting them towards the behavior probe. Such a direct parameter editing method necessitates only inference-level computational resources. Experiments demonstrate that in the representative detoxification task, our approach achieves reductions of up to 90.0\% in toxicity on the RealToxicityPrompts dataset and 49.2\% on ToxiGen, while maintaining the LLM's general capabilities in areas such as common sense, question answering, and mathematics. Our code is available at https://github.com/lucywang720/model-surgery.

Prediction problems often admit competing models that perform almost equally well. This effect challenges key assumptions in machine learning when competing models assign conflicting predictions. In this paper, we define predictive multiplicity as the ability of a prediction problem to admit competing models with conflicting predictions. We introduce formal measures to evaluate the severity of predictive multiplicity and develop integer programming tools to compute them exactly for linear classification problems. We apply our tools to measure predictive multiplicity in recidivism prediction problems. Our results show that real-world datasets may admit competing models that assign wildly conflicting predictions, and motivate the need to measure and report predictive multiplicity in model development.

Predictive multiplicity refers to the phenomenon in which classification tasks may admit multiple competing models that achieve almost-equally-optimal performance, yet generate conflicting outputs for individual samples. This presents significant concerns, as it can potentially result in systemic exclusion, inexplicable discrimination, and unfairness in practical applications. Measuring and mitigating predictive multiplicity, however, is computationally challenging due to the need to explore all such almost-equally-optimal models, known as the Rashomon set, in potentially huge hypothesis spaces. To address this challenge, we propose a novel framework that utilizes dropout techniques for exploring models in the Rashomon set. We provide rigorous theoretical derivations to connect the dropout parameters to properties of the Rashomon set, and empirically evaluate our framework through extensive experimentation. Numerical results show that our technique consistently outperforms baselines in terms of the effectiveness of predictive multiplicity metric estimation, with runtime speedup up to 20times sim 5000times. With efficient Rashomon set exploration and metric estimation, mitigation of predictive multiplicity is then achieved through dropout ensemble and model selection.

During the development of large language models (LLMs), pre-training data play a critical role in shaping LLMs' capabilities. In recent years several large-scale and high-quality pre-training datasets have been released to accelerate the research of LLMs, including ChineseWebText1.0, C4, Pile, WanJuan, MAPCC and others. However, as LLMs continue to evolve, focus has increasingly shifted to domain-specific capabilities and safety concerns, making those previous coarse-grained texts insufficient for meeting training requirements. Furthermore, fine-grained information, such as quality, domain and toxicity, is becoming increasingly important in building powerful and reliable LLMs for various scenarios. To address these challenges, in this paper we propose a new tool-chain called MDFG-tool for constructing large-scale and high-quality Chinese datasets with multi-dimensional and fine-grained information. First, we employ manually crafted rules to discard explicit noisy texts from raw contents. Second, the quality evaluation model, domain classifier, and toxicity evaluation model are well-designed to assess the remaining cleaned data respectively. Finally, we integrate these three types of fine-grained information for each text. With this approach, we release the largest, high-quality and fine-grained Chinese text ChineseWebText2.0, which consists of 3.8TB and each text is associated with a quality score, domain labels, a toxicity label and a toxicity score, facilitating the LLM researchers to select data based on various types of fine-grained information. The data, codes and the tool-chain are available on this website https://github.com/CASIA-LM/ChineseWebText-2.0

This paper investigates using knowledge editing techniques to detoxify Large Language Models (LLMs). We construct a benchmark, SafeEdit, which covers nine unsafe categories with various powerful attack prompts and equips comprehensive metrics for systematic evaluation. We conduct experiments to compare knowledge editing approaches with previous baselines, indicating that knowledge editing has the potential to efficiently detoxify LLMs with limited impact on general performance. Then, we propose a simple yet effective baseline, dubbed Detoxifying with Intraoperative Neural Monitoring (DINM), to diminish the toxicity of LLMs within a few tuning steps via only one instance. We further provide an in-depth analysis of the internal mechanism for various detoxify approaches, demonstrating that previous methods like SFT and DPO may merely suppress the activations of toxic parameters, while DINM mitigates the toxicity of the toxic parameters to a certain extent, making permanent adjustments. We hope that these insights could shed light on future work of developing detoxifying approaches and the underlying knowledge mechanisms of LLMs. Code and benchmark are available at https://github.com/zjunlp/EasyEdit.

AI-driven discovery can greatly reduce design time and enhance new therapeutics' effectiveness. Models using simulators explore broad design spaces but risk violating implicit constraints due to a lack of experimental priors. For example, in a new analysis we performed on a diverse set of models on the GuacaMol benchmark using supervised classifiers, over 60\% of molecules proposed had high probability of being mutagenic. In this work, we introduce \ourdataset, a dataset of priors for design problems extracted from literature describing compounds used in lab settings. It is constructed with LLM pipelines for discovering therapeutic entities in relevant paragraphs and summarizing information in concise fair-use facts. \ourdataset~ consists of 32.3 million pairs of natural language facts, and appropriate entity representations (i.e. SMILES or refseq IDs). To demonstrate the potential of the data, we train LLM, CLIP, and LLava architectures to reason jointly about text and design targets and evaluate on tasks from the Therapeutic Data Commons (TDC). \ourdataset~is highly effective for creating models with strong priors: in supervised prediction problems that use our data as pretraining, our best models with 15M learnable parameters outperform larger 2B TxGemma on both regression and classification TDC tasks, and perform comparably to 9B models on average. Models built with \ourdataset~can be used as constraints while optimizing for novel molecules in GuacaMol, resulting in proposals that are safer and nearly as effective. We release our dataset at https://huggingface.co/datasets/medexanon/Medex{huggingface.co/datasets/medexanon/Medex}, and will provide expanded versions as available literature grows.

Large language models (LLMs) have gained widespread interest due to their ability to process human language and perform tasks on which they have not been explicitly trained. This is relevant for the chemical sciences, which face the problem of small and diverse datasets that are frequently in the form of text. LLMs have shown promise in addressing these issues and are increasingly being harnessed to predict chemical properties, optimize reactions, and even design and conduct experiments autonomously. However, we still have only a very limited systematic understanding of the chemical reasoning capabilities of LLMs, which would be required to improve models and mitigate potential harms. Here, we introduce "ChemBench," an automated framework designed to rigorously evaluate the chemical knowledge and reasoning abilities of state-of-the-art LLMs against the expertise of human chemists. We curated more than 7,000 question-answer pairs for a wide array of subfields of the chemical sciences, evaluated leading open and closed-source LLMs, and found that the best models outperformed the best human chemists in our study on average. The models, however, struggle with some chemical reasoning tasks that are easy for human experts and provide overconfident, misleading predictions, such as about chemicals' safety profiles. These findings underscore the dual reality that, although LLMs demonstrate remarkable proficiency in chemical tasks, further research is critical to enhancing their safety and utility in chemical sciences. Our findings also indicate a need for adaptations to chemistry curricula and highlight the importance of continuing to develop evaluation frameworks to improve safe and useful LLMs.

We present two novel unsupervised methods for eliminating toxicity in text. Our first method combines two recent ideas: (1) guidance of the generation process with small style-conditional language models and (2) use of paraphrasing models to perform style transfer. We use a well-performing paraphraser guided by style-trained language models to keep the text content and remove toxicity. Our second method uses BERT to replace toxic words with their non-offensive synonyms. We make the method more flexible by enabling BERT to replace mask tokens with a variable number of words. Finally, we present the first large-scale comparative study of style transfer models on the task of toxicity removal. We compare our models with a number of methods for style transfer. The models are evaluated in a reference-free way using a combination of unsupervised style transfer metrics. Both methods we suggest yield new SOTA results.

Even with various regulations in place across countries and social media platforms (Government of India, 2021; European Parliament and Council of the European Union, 2022, digital abusive speech remains a significant issue. One potential approach to address this challenge is automatic text detoxification, a text style transfer (TST) approach that transforms toxic language into a more neutral or non-toxic form. To date, the availability of parallel corpora for the text detoxification task (Logachevavet al., 2022; Atwell et al., 2022; Dementievavet al., 2024a) has proven to be crucial for state-of-the-art approaches. With this work, we extend parallel text detoxification corpus to new languages -- German, Chinese, Arabic, Hindi, and Amharic -- testing in the extensive multilingual setup TST baselines. Next, we conduct the first of its kind an automated, explainable analysis of the descriptive features of both toxic and non-toxic sentences, diving deeply into the nuances, similarities, and differences of toxicity and detoxification across 9 languages. Finally, based on the obtained insights, we experiment with a novel text detoxification method inspired by the Chain-of-Thoughts reasoning approach, enhancing the prompting process through clustering on relevant descriptive attributes.

The task of toxicity detection is still a relevant task, especially in the context of safe and fair LMs development. Nevertheless, labeled binary toxicity classification corpora are not available for all languages, which is understandable given the resource-intensive nature of the annotation process. Ukrainian, in particular, is among the languages lacking such resources. To our knowledge, there has been no existing toxicity classification corpus in Ukrainian. In this study, we aim to fill this gap by investigating cross-lingual knowledge transfer techniques and creating labeled corpora by: (i)~translating from an English corpus, (ii)~filtering toxic samples using keywords, and (iii)~annotating with crowdsourcing. We compare LLMs prompting and other cross-lingual transfer approaches with and without fine-tuning offering insights into the most robust and efficient baselines.

Low-rank approximation techniques have become the de facto standard for fine-tuning Large Language Models (LLMs) due to their reduced computational and memory requirements. This paper investigates the effectiveness of these methods in capturing the shift of fine-tuning datasets from the initial pre-trained data distribution. Our findings reveal that there are cases in which low-rank fine-tuning falls short in learning such shifts. This, in turn, produces non-negligible side effects, especially when fine-tuning is adopted for toxicity mitigation in pre-trained models, or in scenarios where it is important to provide fair models. Through comprehensive empirical evidence on several models, datasets, and tasks, we show that low-rank fine-tuning inadvertently preserves undesirable biases and toxic behaviors. We also show that this extends to sequential decision-making tasks, emphasizing the need for careful evaluation to promote responsible LLMs development.

The recent success of large foundation models in artificial intelligence has prompted the emergence of chemical pre-trained models. Despite the growing interest in large molecular pre-trained models that provide informative representations for downstream tasks, attempts for multimodal pre-training approaches on the molecule domain were limited. To address this, we present a novel multimodal molecular pre-trained model that incorporates the modalities of structure and biochemical properties, drawing inspiration from recent advances in multimodal learning techniques. Our proposed model pipeline of data handling and training objectives aligns the structure/property features in a common embedding space, which enables the model to regard bidirectional information between the molecules' structure and properties. These contributions emerge synergistic knowledge, allowing us to tackle both multimodal and unimodal downstream tasks through a single model. Through extensive experiments, we demonstrate that our model shows remarkable capabilities in solving various meaningful chemical challenges, including conditional molecule generation, property prediction, molecule classification, and reaction prediction.

Large language models (LLMs) are now ubiquitous in user-facing applications, yet they still generate undesirable toxic outputs, including profanity, vulgarity, and derogatory remarks. Although numerous detoxification methods exist, most apply broad, surface-level fixes and can therefore easily be circumvented by jailbreak attacks. In this paper we leverage sparse autoencoders (SAEs) to identify toxicity-related directions in the residual stream of models and perform targeted activation steering using the corresponding decoder vectors. We introduce three tiers of steering aggressiveness and evaluate them on GPT-2 Small and Gemma-2-2B, revealing trade-offs between toxicity reduction and language fluency. At stronger steering strengths, these causal interventions surpass competitive baselines in reducing toxicity by up to 20%, though fluency can degrade noticeably on GPT-2 Small depending on the aggressiveness. Crucially, standard NLP benchmark scores upon steering remain stable, indicating that the model's knowledge and general abilities are preserved. We further show that feature-splitting in wider SAEs hampers safety interventions, underscoring the importance of disentangled feature learning. Our findings highlight both the promise and the current limitations of SAE-based causal interventions for LLM detoxification, further suggesting practical guidelines for safer language-model deployment.

Cancer is the second leading cause of death, with chemotherapy as one of the primary forms of treatment. As a result, researchers are turning to drug combination therapy to decrease drug resistance and increase efficacy. Current methods of drug combination screening, such as in vivo and in vitro, are inefficient due to stark time and monetary costs. In silico methods have become increasingly important for screening drugs, but current methods are inaccurate and generalize poorly to unseen anticancer drugs. In this paper, I employ a geometric deep-learning model utilizing a graph attention network that is equivariant to 3D rotations, translations, and reflections with structural motifs. Additionally, the gene expression of cancer cell lines is utilized to classify synergistic drug combinations specific to each cell line. I compared the proposed geometric deep learning framework to current state-of-the-art (SOTA) methods, and the proposed model architecture achieved greater performance on all 12 benchmark tasks performed on the DrugComb dataset. Specifically, the proposed framework outperformed other SOTA methods by an accuracy difference greater than 28%. Based on these results, I believe that the equivariant graph attention network's capability of learning geometric data accounts for the large performance improvements. The model's ability to generalize to foreign drugs is thought to be due to the structural motifs providing a better representation of the molecule. Overall, I believe that the proposed equivariant geometric deep learning framework serves as an effective tool for virtually screening anticancer drug combinations for further validation in a wet lab environment. The code for this work is made available online at: https://github.com/WeToTheMoon/EGAT_DrugSynergy.

With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the relationships among different applications. The latest literature and classical benchmarks are presented for better understanding the development of variety of approaches. We commence by summarizing the molecule representation format in these works, followed by an introduction of recent proposed approaches for each of the four tasks. Furthermore, we review a variety of commonly used datasets and evaluation metrics and compare the performance of deep learning-based models. Finally, we conclude by identifying remaining challenges and discussing the future trend for deep learning methods in drug discovery.

As generative large language models (LLMs) grow more performant and prevalent, we must develop comprehensive enough tools to measure and improve their fairness. Different prompt-based datasets can be used to measure social bias across multiple text domains and demographic axes, meaning that testing LLMs on more datasets can potentially help us characterize their biases more fully, and better ensure equal and equitable treatment of marginalized demographic groups. In this work, our focus is two-fold: (1) Benchmarking: a comparison of 6 different prompt-based bias and toxicity metrics across 12 demographic axes and 5 families of generative LLMs. Out of those 6 metrics, AdvPromptSet and HolisticBiasR are novel datasets proposed in the paper. The comparison of those benchmarks gives us insights about the bias and toxicity of the compared models. Therefore, we explore the frequency of demographic terms in common LLM pre-training corpora and how this may relate to model biases. (2) Mitigation: we conduct a comprehensive study of how well 3 bias/toxicity mitigation techniques perform across our suite of measurements. ROBBIE aims to provide insights for practitioners while deploying a model, emphasizing the need to not only measure potential harms, but also understand how they arise by characterizing the data, mitigate harms once found, and balance any trade-offs. We open-source our analysis code in hopes of encouraging broader measurements of bias in future LLMs.

High-throughput drug screening -- using cell imaging or gene expression measurements as readouts of drug effect -- is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. The code is available at https://github.com/uhlerlab/InfoCORE.

Caution: This paper includes offensive words that could potentially cause unpleasantness. The fast-paced evolution of generative language models such as GPT-4 has demonstrated outstanding results in various NLP generation tasks. However, due to the potential generation of offensive words related to race or gender, various Controllable Text Generation (CTG) methods have been proposed to mitigate the occurrence of harmful words. However, existing CTG methods not only reduce toxicity but also negatively impact several aspects of the language model's generation performance, including topic consistency, grammar, and perplexity. This paper explores the limitations of previous methods and introduces a novel solution in the form of a simple Gated Toxicity Avoidance (GTA) that can be applied to any CTG method. We also evaluate the effectiveness of the proposed GTA by comparing it with state-of-the-art CTG methods across various datasets. Our findings reveal that gated toxicity avoidance efficiently achieves comparable levels of toxicity reduction to the original CTG methods while preserving the generation performance of the language model.

We present a novel approach for the prediction of anticancer compound sensitivity by means of multi-modal attention-based neural networks (PaccMann). In our approach, we integrate three key pillars of drug sensitivity, namely, the molecular structure of compounds, transcriptomic profiles of cancer cells as well as prior knowledge about interactions among proteins within cells. Our models ingest a drug-cell pair consisting of SMILES encoding of a compound and the gene expression profile of a cancer cell and predicts an IC50 sensitivity value. Gene expression profiles are encoded using an attention-based encoding mechanism that assigns high weights to the most informative genes. We present and study three encoders for SMILES string of compounds: 1) bidirectional recurrent 2) convolutional 3) attention-based encoders. We compare our devised models against a baseline model that ingests engineered fingerprints to represent the molecular structure. We demonstrate that using our attention-based encoders, we can surpass the baseline model. The use of attention-based encoders enhance interpretability and enable us to identify genes, bonds and atoms that were used by the network to make a prediction.

As the capabilities of Large Language Models (LLMs) in healthcare and medicine continue to advance, there is a growing need for competitive open-source models that can safeguard public interest. With the increasing availability of highly competitive open base models, the impact of continued pre-training is increasingly uncertain. In this work, we explore the role of instruct tuning, model merging, alignment, red teaming and advanced inference schemes, as means to improve current open models. To that end, we introduce the Aloe family, a set of open medical LLMs highly competitive within its scale range. Aloe models are trained on the current best base models (Mistral, LLaMA 3), using a new custom dataset which combines public data sources improved with synthetic Chain of Thought (CoT). Aloe models undergo an alignment phase, becoming one of the first few policy-aligned open healthcare LLM using Direct Preference Optimization, setting a new standard for ethical performance in healthcare LLMs. Model evaluation expands to include various bias and toxicity datasets, a dedicated red teaming effort, and a much-needed risk assessment for healthcare LLMs. Finally, to explore the limits of current LLMs in inference, we study several advanced prompt engineering strategies to boost performance across benchmarks, yielding state-of-the-art results for open healthcare 7B LLMs, unprecedented at this scale.

Large language models (LLMs) have shown incredible capabilities and transcended the natural language processing (NLP) community, with adoption throughout many services like healthcare, therapy, education, and customer service. Since users include people with critical information needs like students or patients engaging with chatbots, the safety of these systems is of prime importance. Therefore, a clear understanding of the capabilities and limitations of LLMs is necessary. To this end, we systematically evaluate toxicity in over half a million generations of ChatGPT, a popular dialogue-based LLM. We find that setting the system parameter of ChatGPT by assigning it a persona, say that of the boxer Muhammad Ali, significantly increases the toxicity of generations. Depending on the persona assigned to ChatGPT, its toxicity can increase up to 6x, with outputs engaging in incorrect stereotypes, harmful dialogue, and hurtful opinions. This may be potentially defamatory to the persona and harmful to an unsuspecting user. Furthermore, we find concerning patterns where specific entities (e.g., certain races) are targeted more than others (3x more) irrespective of the assigned persona, that reflect inherent discriminatory biases in the model. We hope that our findings inspire the broader AI community to rethink the efficacy of current safety guardrails and develop better techniques that lead to robust, safe, and trustworthy AI systems.

The rapid development of large Vision-Language Models (VLMs) has led to impressive results on academic benchmarks, primarily in widely spoken languages. However, significant gaps remain in the ability of current VLMs to handle low-resource languages and varied cultural contexts, largely due to a lack of high-quality, diverse, and safety-vetted data. Consequently, these models often struggle to understand low-resource languages and cultural nuances in a manner free from toxicity. To address these limitations, we introduce Maya, an open-source Multimodal Multilingual model. Our contributions are threefold: 1) a multilingual image-text pretraining dataset in eight languages, based on the LLaVA pretraining dataset; 2) a thorough analysis of toxicity within the LLaVA dataset, followed by the creation of a novel toxicity-free version across eight languages; and 3) a multilingual image-text model supporting these languages, enhancing cultural and linguistic comprehension in vision-language tasks. Code available at https://github.com/nahidalam/maya.

Toxic language detection systems often falsely flag text that contains minority group mentions as toxic, as those groups are often the targets of online hate. Such over-reliance on spurious correlations also causes systems to struggle with detecting implicitly toxic language. To help mitigate these issues, we create ToxiGen, a new large-scale and machine-generated dataset of 274k toxic and benign statements about 13 minority groups. We develop a demonstration-based prompting framework and an adversarial classifier-in-the-loop decoding method to generate subtly toxic and benign text with a massive pretrained language model. Controlling machine generation in this way allows ToxiGen to cover implicitly toxic text at a larger scale, and about more demographic groups, than previous resources of human-written text. We conduct a human evaluation on a challenging subset of ToxiGen and find that annotators struggle to distinguish machine-generated text from human-written language. We also find that 94.5% of toxic examples are labeled as hate speech by human annotators. Using three publicly-available datasets, we show that finetuning a toxicity classifier on our data improves its performance on human-written data substantially. We also demonstrate that ToxiGen can be used to fight machine-generated toxicity as finetuning improves the classifier significantly on our evaluation subset. Our code and data can be found at https://github.com/microsoft/ToxiGen.

High-throughput reaction condition (RC) screening is fundamental to chemical synthesis. However, current RC screening suffers from laborious and costly trial-and-error workflows. Traditional computer-aided synthesis planning (CASP) tools fail to find suitable RCs due to data sparsity and inadequate reaction representations. Nowadays, large language models (LLMs) are capable of tackling chemistry-related problems, such as molecule design, and chemical logic Q\&A tasks. However, LLMs have not yet achieved accurate predictions of chemical reaction conditions. Here, we present MM-RCR, a text-augmented multimodal LLM that learns a unified reaction representation from SMILES, reaction graphs, and textual corpus for chemical reaction recommendation (RCR). To train MM-RCR, we construct 1.2 million pair-wised Q\&A instruction datasets. Our experimental results demonstrate that MM-RCR achieves state-of-the-art performance on two open benchmark datasets and exhibits strong generalization capabilities on out-of-domain (OOD) and High-Throughput Experimentation (HTE) datasets. MM-RCR has the potential to accelerate high-throughput condition screening in chemical synthesis.

An important issue with Large Language Models (LLMs) is their undesired ability to generate toxic language. In this work, we show that the neurons responsible for toxicity can be determined by their power to discriminate toxic sentences, and that toxic language can be mitigated by reducing their activation levels proportionally to this power. We propose AUROC adaptation (AurA), an intervention that can be applied to any pre-trained LLM to mitigate toxicity. As the intervention is proportional to the ability of each neuron to discriminate toxic content, it is free of any model-dependent hyperparameters. We show that AurA can achieve up to 2.2 times reduction in toxicity with only a 0.72 perplexity increase. We also show that AurA is effective with models of different scale (from 1.5B to 40B parameters), and its effectiveness in mitigating toxic language, while preserving common-sense zero-shot abilities, holds across all scales. AurA can be combined with pre-prompting strategies, boosting its average mitigation potential from 1.28times to 2.35times. Moreover, AurA can counteract adversarial pre-prompts that maliciously elicit toxic content, making it an effective method for deploying safer and less toxic models.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient recruitment. If we were better at predicting the results of clinical trials, we could avoid having to run trials that will inevitably fail more resources could be devoted to trials that are likely to succeed. In this paper, we propose Hierarchical INteraction Network (HINT) for more general, clinical trial outcome predictions for all diseases based on a comprehensive and diverse set of web data including molecule information of the drugs, target disease information, trial protocol and biomedical knowledge. HINT first encode these multi-modal data into latent embeddings, where an imputation module is designed to handle missing data. Next, these embeddings will be fed into the knowledge embedding module to generate knowledge embeddings that are pretrained using external knowledge on pharmaco-kinetic properties and trial risk from the web. Then the interaction graph module will connect all the embedding via domain knowledge to fully capture various trial components and their complex relations as well as their influences on trial outcomes. Finally, HINT learns a dynamic attentive graph neural network to predict trial outcome. Comprehensive experimental results show that HINT achieves strong predictive performance, obtaining 0.772, 0.607, 0.623, 0.703 on PR-AUC for Phase I, II, III, and indication outcome prediction, respectively. It also consistently outperforms the best baseline method by up to 12.4\% on PR-AUC.

Text detoxification is the task of transferring the style of text from toxic to neutral. While here are approaches yielding promising results in monolingual setup, e.g., (Dale et al., 2021; Hallinan et al., 2022), cross-lingual transfer for this task remains a challenging open problem (Moskovskiy et al., 2022). In this work, we present a large-scale study of strategies for cross-lingual text detoxification -- given a parallel detoxification corpus for one language; the goal is to transfer detoxification ability to another language for which we do not have such a corpus. Moreover, we are the first to explore a new task where text translation and detoxification are performed simultaneously, providing several strong baselines for this task. Finally, we introduce new automatic detoxification evaluation metrics with higher correlations with human judgments than previous benchmarks. We assess the most promising approaches also with manual markup, determining the answer for the best strategy to transfer the knowledge of text detoxification between languages.

Advancements in high-throughput technologies have led to a shift from traditional hypothesis-driven methodologies to data-driven approaches. Multi-omics refers to the integrative analysis of data derived from multiple 'omes', such as genomics, proteomics, transcriptomics, metabolomics, and microbiomics. This approach enables a comprehensive understanding of biological systems by capturing different layers of biological information. Deep learning methods are increasingly utilized to integrate multi-omics data, offering insights into molecular interactions and enhancing research into complex diseases. However, these models, with their numerous interconnected layers and nonlinear relationships, often function as black boxes, lacking transparency in decision-making processes. To overcome this challenge, explainable artificial intelligence (xAI) methods are crucial for creating transparent models that allow clinicians to interpret and work with complex data more effectively. This review explores how xAI can improve the interpretability of deep learning models in multi-omics research, highlighting its potential to provide clinicians with clear insights, thereby facilitating the effective application of such models in clinical settings.

Accurately classifying chemical structures is essential for cheminformatics and bioinformatics, including tasks such as identifying bioactive compounds of interest, screening molecules for toxicity to humans, finding non-organic compounds with desirable material properties, or organizing large chemical libraries for drug discovery or environmental monitoring. However, manual classification is labor-intensive and difficult to scale to large chemical databases. Existing automated approaches either rely on manually constructed classification rules, or the use of deep learning methods that lack explainability. This work presents an approach that uses generative artificial intelligence to automatically write chemical classifier programs for classes in the Chemical Entities of Biological Interest (ChEBI) database. These programs can be used for efficient deterministic run-time classification of SMILES structures, with natural language explanations. The programs themselves constitute an explainable computable ontological model of chemical class nomenclature, which we call the ChEBI Chemical Class Program Ontology (C3PO). We validated our approach against the ChEBI database, and compared our results against state of the art deep learning models. We also demonstrate the use of C3PO to classify out-of-distribution examples taken from metabolomics repositories and natural product databases. We also demonstrate the potential use of our approach to find systematic classification errors in existing chemical databases, and show how an ensemble artificial intelligence approach combining generated ontologies, automated literature search, and multimodal vision models can be used to pinpoint potential errors requiring expert validation

Toxic comment detection remains a challenging task, where transformer-based models (e.g., BERT) incur high computational costs and degrade on minority toxicity classes, while classical ensembles lack semantic adaptability. We propose xLSTM, a parameter-efficient and theoretically grounded framework that unifies cosine-similarity gating, adaptive feature prioritization, and principled class rebalancing. A learnable reference vector {v} in {R}^d modulates contextual embeddings via cosine similarity, amplifying toxic cues and attenuating benign signals to yield stronger gradients under severe class imbalance. xLSTM integrates multi-source embeddings (GloVe, FastText, BERT CLS) through a projection layer, a character-level BiLSTM for morphological cues, embedding-space SMOTE for minority augmentation, and adaptive focal loss with dynamic class weighting. On the Jigsaw Toxic Comment benchmark, xLSTM attains 96.0% accuracy and 0.88 macro-F1, outperforming BERT by 33% on threat and 28% on identity_hate categories, with 15 times fewer parameters and 50ms inference latency. Cosine gating contributes a +4.8% F1 gain in ablations. The results establish a new efficiency adaptability frontier, demonstrating that lightweight, theoretically informed architectures can surpass large pretrained models on imbalanced, domain-specific NLP tasks.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

Protein-ligand binding affinity prediction is essential for drug discovery and toxicity assessment. While machine learning (ML) promises fast and accurate predictions, its progress is constrained by the availability of reliable data. In contrast, physics-based methods such as absolute binding free energy perturbation (AB-FEP) deliver high accuracy but are computationally prohibitive for high-throughput applications. To bridge this gap, we introduce ToxBench, the first large-scale AB-FEP dataset designed for ML development and focused on a single pharmaceutically critical target, Human Estrogen Receptor Alpha (ERalpha). ToxBench contains 8,770 ERalpha-ligand complex structures with binding free energies computed via AB-FEP with a subset validated against experimental affinities at 1.75 kcal/mol RMSE, along with non-overlapping ligand splits to assess model generalizability. Using ToxBench, we further benchmark state-of-the-art ML methods, and notably, our proposed DualBind model, which employs a dual-loss framework to effectively learn the binding energy function. The benchmark results demonstrate the superior performance of DualBind and the potential of ML to approximate AB-FEP at a fraction of the computational cost.

Drug discovery is a complex and time-intensive process that requires identifying and validating new therapeutic candidates. Computational approaches using large-scale biomedical knowledge graphs (KGs) offer a promising solution to accelerate this process. However, extracting meaningful insights from large-scale KGs remains challenging due to the complexity of graph traversal. Existing subgraph-based methods are tailored to graph neural networks (GNNs), making them incompatible with other models, such as large language models (LLMs). We introduce K-Paths, a retrieval framework that extracts structured, diverse, and biologically meaningful paths from KGs. Integrating these paths enables LLMs and GNNs to effectively predict unobserved drug-drug and drug-disease interactions. Unlike traditional path-ranking approaches, K-Paths retrieves and transforms paths into a structured format that LLMs can directly process, facilitating explainable reasoning. K-Paths employs a diversity-aware adaptation of Yen's algorithm to retrieve the K shortest loopless paths between entities in an interaction query, prioritizing biologically relevant and diverse relationships. Our experiments on benchmark datasets show that K-Paths improves the zero-shot performance of Llama 8.1B's F1-score by 12.45 points on drug repurposing and 13.42 points on interaction severity prediction. We also show that Llama 70B achieves F1-score gains of 6.18 and 8.46 points, respectively. K-Paths also improves the supervised training efficiency of EmerGNN, a state-of-the-art GNN, by reducing KG size by 90% while maintaining strong predictive performance. Beyond its scalability and efficiency, K-Paths uniquely bridges the gap between KGs and LLMs, providing explainable rationales for predicted interactions. These capabilities show that K-Paths is a valuable tool for efficient data-driven drug discovery.

Pretrained neural networks have attracted significant interest in chemistry and small molecule drug design. Embeddings from these models are widely used for molecular property prediction, virtual screening, and small data learning in molecular chemistry. This study presents the most extensive comparison of such models to date, evaluating 25 models across 25 datasets. Under a fair comparison framework, we assess models spanning various modalities, architectures, and pretraining strategies. Using a dedicated hierarchical Bayesian statistical testing model, we arrive at a surprising result: nearly all neural models show negligible or no improvement over the baseline ECFP molecular fingerprint. Only the CLAMP model, which is also based on molecular fingerprints, performs statistically significantly better than the alternatives. These findings raise concerns about the evaluation rigor in existing studies. We discuss potential causes, propose solutions, and offer practical recommendations.

Combination therapies have become the standard of care for diseases such as cancer, tuberculosis, malaria and HIV. However, the combinatorial set of available multi-drug treatments creates a challenge in identifying effective combination therapies available in a situation. To assist medical professionals in identifying beneficial drug-combinations, we construct an expert-annotated dataset for extracting information about the efficacy of drug combinations from the scientific literature. Beyond its practical utility, the dataset also presents a unique NLP challenge, as the first relation extraction dataset consisting of variable-length relations. Furthermore, the relations in this dataset predominantly require language understanding beyond the sentence level, adding to the challenge of this task. We provide a promising baseline model and identify clear areas for further improvement. We release our dataset, code, and baseline models publicly to encourage the NLP community to participate in this task.

The common toxicity and societal bias in contents generated by large language models (LLMs) necessitate strategies to reduce harm. Present solutions often demand white-box access to the model or substantial training, which is impractical for cutting-edge commercial LLMs. Moreover, prevailing prompting methods depend on external tool feedback and fail to simultaneously lessen toxicity and bias. Motivated by social psychology principles, we propose a novel strategy named perspective-taking prompting (\textsc{PeT)} that inspires LLMs to integrate diverse human perspectives and self-regulate their responses. This self-correction mechanism can significantly diminish toxicity (up to 89%) and bias (up to 73%) in LLMs' responses. Rigorous evaluations and ablation studies are conducted on two commercial LLMs (ChatGPT and GLM) and three open-source LLMs, revealing PeT's superiority in producing less harmful responses, outperforming five strong baselines.

Early identification of sensitive cancer cell lines is essential for accelerating biomarker discovery and elucidating drug mechanism of action. Given the efficiency and low cost of small-scale drug screens relative to extensive omics profiling, we compared drug-response panel (DRP) descriptors against omics features for predictive capacity using gradient boosting tree models across the GDSC and CCLE drug response datasets. DRP descriptors consistently outperformed omics data across key performance metrics, with variable performance across different drugs. Using complementary explainability approaches, we confirmed known MAPK-inhibitor sensitivity signatures, and identified novel potential biomarker candidates for MEK1/2 and BTK/MNK inhibitors. Lastly, to demonstrate the utility of this approach in distinguishing phenotypes, we applied our models to the breast cancer line MCF7 versus the non-tumorigenic MCF10A, and successfully identified compounds that selectively inhibit MCF7 while sparing the non-tumorigenic MCF10A. This methodology, developed using focused drug and cell line panels, supports early-stage drug development by facilitating rational cell line selection and compound prioritisation, enabling more efficient biomarker identification and candidate assessment.

We develop a method to generate predictive regions that cover a multivariate response variable with a user-specified probability. Our work is composed of two components. First, we use a deep generative model to learn a representation of the response that has a unimodal distribution. Existing multiple-output quantile regression approaches are effective in such cases, so we apply them on the learned representation, and then transform the solution to the original space of the response. This process results in a flexible and informative region that can have an arbitrary shape, a property that existing methods lack. Second, we propose an extension of conformal prediction to the multivariate response setting that modifies any method to return sets with a pre-specified coverage level. The desired coverage is theoretically guaranteed in the finite-sample case for any distribution. Experiments conducted on both real and synthetic data show that our method constructs regions that are significantly smaller compared to existing techniques.

Understanding the vulnerabilities of Large Vision Language Models (LVLMs) to jailbreak attacks is essential for their responsible real-world deployment. Most previous work requires access to model gradients, or is based on human knowledge (prompt engineering) to complete jailbreak, and they hardly consider the interaction of images and text, resulting in inability to jailbreak in black box scenarios or poor performance. To overcome these limitations, we propose a Prior-Guided Bimodal Interactive Black-Box Jailbreak Attack for toxicity maximization, referred to as PBI-Attack. Our method begins by extracting malicious features from a harmful corpus using an alternative LVLM and embedding these features into a benign image as prior information. Subsequently, we enhance these features through bidirectional cross-modal interaction optimization, which iteratively optimizes the bimodal perturbations in an alternating manner through greedy search, aiming to maximize the toxicity of the generated response. The toxicity level is quantified using a well-trained evaluation model. Experiments demonstrate that PBI-Attack outperforms previous state-of-the-art jailbreak methods, achieving an average attack success rate of 92.5% across three open-source LVLMs and around 67.3% on three closed-source LVLMs. Disclaimer: This paper contains potentially disturbing and offensive content.

Recent research in representation learning utilizes large databases of proteins or molecules to acquire knowledge of drug and protein structures through unsupervised learning techniques. These pre-trained representations have proven to significantly enhance the accuracy of subsequent tasks, such as predicting the affinity between drugs and target proteins. In this study, we demonstrate that by incorporating knowledge graphs from diverse sources and modalities into the sequences or SMILES representation, we can further enrich the representation and achieve state-of-the-art results on established benchmark datasets. We provide preprocessed and integrated data obtained from 7 public sources, which encompass over 30M triples. Additionally, we make available the pre-trained models based on this data, along with the reported outcomes of their performance on three widely-used benchmark datasets for drug-target binding affinity prediction found in the Therapeutic Data Commons (TDC) benchmarks. Additionally, we make the source code for training models on benchmark datasets publicly available. Our objective in releasing these pre-trained models, accompanied by clean data for model pretraining and benchmark results, is to encourage research in knowledge-enhanced representation learning.

Developing therapeutics is a lengthy and expensive process that requires the satisfaction of many different criteria, and AI models capable of expediting the process would be invaluable. However, the majority of current AI approaches address only a narrowly defined set of tasks, often circumscribed within a particular domain. To bridge this gap, we introduce Tx-LLM, a generalist large language model (LLM) fine-tuned from PaLM-2 which encodes knowledge about diverse therapeutic modalities. Tx-LLM is trained using a collection of 709 datasets that target 66 tasks spanning various stages of the drug discovery pipeline. Using a single set of weights, Tx-LLM simultaneously processes a wide variety of chemical or biological entities(small molecules, proteins, nucleic acids, cell lines, diseases) interleaved with free-text, allowing it to predict a broad range of associated properties, achieving competitive with state-of-the-art (SOTA) performance on 43 out of 66 tasks and exceeding SOTA on 22. Among these, Tx-LLM is particularly powerful and exceeds best-in-class performance on average for tasks combining molecular SMILES representations with text such as cell line names or disease names, likely due to context learned during pretraining. We observe evidence of positive transfer between tasks with diverse drug types (e.g.,tasks involving small molecules and tasks involving proteins), and we study the impact of model size, domain finetuning, and prompting strategies on performance. We believe Tx-LLM represents an important step towards LLMs encoding biochemical knowledge and could have a future role as an end-to-end tool across the drug discovery development pipeline.

Safety fine-tuning algorithms are commonly used to fine-tune language models to reduce harmful outputs, but the exact internal mechanisms of how those models achieve this remain unclear. In studying direct preference optimisation (DPO) for toxicity reduction, current explanations claim that DPO works by dampening the most toxic MLP neurons to learn an offset to avert toxic regions in the residual stream. However, by ablating the most toxic neurons and applying activation patching, we find this explanation incomplete. By projecting neuron activation changes onto a toxicity probe, we find that only 31.8\% of toxicity reduction comes from dampened toxic neurons. Instead, DPO reduces toxicity by accumulating effects across multiple neuron groups, both reducing writing in the toxic direction and promoting anti-toxicity in the residual stream. Moreover, DPO gives noisy adjustments to neuron activations, with many neurons actually increasing toxicity. This indicates that DPO is a balancing process between opposing neuron effects to achieve toxicity reduction.

The success of drug discovery and development relies on the precise prediction of molecular activities and properties. While in silico molecular property prediction has shown remarkable potential, its use has been limited so far to assays for which large amounts of data are available. In this study, we use a fine-tuned large language model to integrate biological assays based on their textual information, coupled with Barlow Twins, a Siamese neural network using a novel self-supervised learning approach. This architecture uses both assay information and molecular fingerprints to extract the true molecular information. TwinBooster enables the prediction of properties of unseen bioassays and molecules by providing state-of-the-art zero-shot learning tasks. Remarkably, our artificial intelligence pipeline shows excellent performance on the FS-Mol benchmark. This breakthrough demonstrates the application of deep learning to critical property prediction tasks where data is typically scarce. By accelerating the early identification of active molecules in drug discovery and development, this method has the potential to help streamline the identification of novel therapeutics.

The ideal LLM content moderation system would be both structurally interpretable (so its decisions can be explained to users) and steerable (to reflect a community's values or align to safety standards). However, current systems fall short on both of these dimensions. To address this gap, we present SafetyAnalyst, a novel LLM safety moderation framework. Given a prompt, SafetyAnalyst creates a structured "harm-benefit tree," which identifies 1) the actions that could be taken if a compliant response were provided, 2) the harmful and beneficial effects of those actions (along with their likelihood, severity, and immediacy), and 3) the stakeholders that would be impacted by those effects. It then aggregates this structured representation into a harmfulness score based on a parameterized set of safety preferences, which can be transparently aligned to particular values. Using extensive harm-benefit features generated by SOTA LLMs on 19k prompts, we fine-tuned an open-weight LM to specialize in generating harm-benefit trees through symbolic knowledge distillation. On a comprehensive set of prompt safety benchmarks, we show that our system (average F1=0.75) outperforms existing LLM safety moderation systems (average F1<0.72) on prompt harmfulness classification, while offering the additional advantages of interpretability and steerability.

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

This paper presents a dataset with over 3.3M threads and 134.5M posts from the Politically Incorrect board (/pol/) of the imageboard forum 4chan, posted over a period of almost 3.5 years (June 2016-November 2019). To the best of our knowledge, this represents the largest publicly available 4chan dataset, providing the community with an archive of posts that have been permanently deleted from 4chan and are otherwise inaccessible. We augment the data with a set of additional labels, including toxicity scores and the named entities mentioned in each post. We also present a statistical analysis of the dataset, providing an overview of what researchers interested in using it can expect, as well as a simple content analysis, shedding light on the most prominent discussion topics, the most popular entities mentioned, and the toxicity level of each post. Overall, we are confident that our work will motivate and assist researchers in studying and understanding 4chan, as well as its role on the greater Web. For instance, we hope this dataset may be used for cross-platform studies of social media, as well as being useful for other types of research like natural language processing. Finally, our dataset can assist qualitative work focusing on in-depth case studies of specific narratives, events, or social theories.

This paper introduces RiskCards, a framework for structured assessment and documentation of risks associated with an application of language models. As with all language, text generated by language models can be harmful, or used to bring about harm. Automating language generation adds both an element of scale and also more subtle or emergent undesirable tendencies to the generated text. Prior work establishes a wide variety of language model harms to many different actors: existing taxonomies identify categories of harms posed by language models; benchmarks establish automated tests of these harms; and documentation standards for models, tasks and datasets encourage transparent reporting. However, there is no risk-centric framework for documenting the complexity of a landscape in which some risks are shared across models and contexts, while others are specific, and where certain conditions may be required for risks to manifest as harms. RiskCards address this methodological gap by providing a generic framework for assessing the use of a given language model in a given scenario. Each RiskCard makes clear the routes for the risk to manifest harm, their placement in harm taxonomies, and example prompt-output pairs. While RiskCards are designed to be open-source, dynamic and participatory, we present a "starter set" of RiskCards taken from a broad literature survey, each of which details a concrete risk presentation. Language model RiskCards initiate a community knowledge base which permits the mapping of risks and harms to a specific model or its application scenario, ultimately contributing to a better, safer and shared understanding of the risk landscape.

Large language models (LLMs) trained with Reinforcement Learning from Human Feedback (RLHF) have demonstrated remarkable capabilities, but their underlying reward functions and decision-making processes remain opaque. This paper introduces a novel approach to interpreting LLMs by applying inverse reinforcement learning (IRL) to recover their implicit reward functions. We conduct experiments on toxicity-aligned LLMs of varying sizes, extracting reward models that achieve up to 80.40% accuracy in predicting human preferences. Our analysis reveals key insights into the non-identifiability of reward functions, the relationship between model size and interpretability, and potential pitfalls in the RLHF process. We demonstrate that IRL-derived reward models can be used to fine-tune new LLMs, resulting in comparable or improved performance on toxicity benchmarks. This work provides a new lens for understanding and improving LLM alignment, with implications for the responsible development and deployment of these powerful systems.

Large Language Models (LLMs) have shown growing potential in molecular sciences, but they often produce chemically inaccurate descriptions and struggle to recognize or justify potential errors. This raises important concerns about their robustness and reliability in scientific applications. To support more rigorous evaluation of LLMs in chemical reasoning, we present the MolErr2Fix benchmark, designed to assess LLMs on error detection and correction in molecular descriptions. Unlike existing benchmarks focused on molecule-to-text generation or property prediction, MolErr2Fix emphasizes fine-grained chemical understanding. It tasks LLMs with identifying, localizing, explaining, and revising potential structural and semantic errors in molecular descriptions. Specifically, MolErr2Fix consists of 1,193 fine-grained annotated error instances. Each instance contains quadruple annotations, i.e,. (error type, span location, the explanation, and the correction). These tasks are intended to reflect the types of reasoning and verification required in real-world chemical communication. Evaluations of current state-of-the-art LLMs reveal notable performance gaps, underscoring the need for more robust chemical reasoning capabilities. MolErr2Fix provides a focused benchmark for evaluating such capabilities and aims to support progress toward more reliable and chemically informed language models. All annotations and an accompanying evaluation API will be publicly released to facilitate future research.

Hit identification is a central challenge in early drug discovery, traditionally requiring substantial experimental resources. Recent advances in artificial intelligence, particularly large language models (LLMs), have enabled virtual screening methods that reduce costs and improve efficiency. However, the growing complexity of these tools has limited their accessibility to wet-lab researchers. Multi-agent systems offer a promising solution by combining the interpretability of LLMs with the precision of specialized models and tools. In this work, we present MADD, a multi-agent system that builds and executes customized hit identification pipelines from natural language queries. MADD employs four coordinated agents to handle key subtasks in de novo compound generation and screening. We evaluate MADD across seven drug discovery cases and demonstrate its superior performance compared to existing LLM-based solutions. Using MADD, we pioneer the application of AI-first drug design to five biological targets and release the identified hit molecules. Finally, we introduce a new benchmark of query-molecule pairs and docking scores for over three million compounds to contribute to the agentic future of drug design.

Disclaimer: Samples in this paper may be harmful and cause discomfort! Patronizing and condescending language (PCL) is a form of speech directed at vulnerable groups. As an essential branch of toxic language, this type of language exacerbates conflicts and confrontations among Internet communities and detrimentally impacts disadvantaged groups. Traditional pre-trained language models (PLMs) perform poorly in detecting PCL due to its implicit toxicity traits like hypocrisy and false sympathy. With the rise of large language models (LLMs), we can harness their rich emotional semantics to establish a paradigm for exploring implicit toxicity. In this paper, we introduce PclGPT, a comprehensive LLM benchmark designed specifically for PCL. We collect, annotate, and integrate the Pcl-PT/SFT dataset, and then develop a bilingual PclGPT-EN/CN model group through a comprehensive pre-training and supervised fine-tuning staircase process to facilitate implicit toxic detection. Group detection results and fine-grained detection from PclGPT and other models reveal significant variations in the degree of bias in PCL towards different vulnerable groups, necessitating increased societal attention to protect them.

Truly multilingual safety moderation efforts for Large Language Models (LLMs) have been hindered by a narrow focus on a small set of languages (e.g., English, Chinese) as well as a limited scope of safety definition, resulting in significant gaps in moderation capabilities. To bridge these gaps, we release POLYGUARD, a new state-of-the-art multilingual safety model for safeguarding LLM generations, and the corresponding training and evaluation datasets. POLYGUARD is trained on POLYGUARDMIX, the largest multilingual safety training corpus to date containing 1.91M samples across 17 languages (e.g., Chinese, Czech, English, Hindi). We also introduce POLYGUARDPROMPTS, a high quality multilingual benchmark with 29K samples for the evaluation of safety guardrails. Created by combining naturally occurring multilingual human-LLM interactions and human-verified machine translations of an English-only safety dataset (WildGuardMix; Han et al., 2024), our datasets contain prompt-output pairs with labels of prompt harmfulness, response harmfulness, and response refusal. Through extensive evaluations across multiple safety and toxicity benchmarks, we demonstrate that POLYGUARD outperforms existing state-of-the-art open-weight and commercial safety classifiers by 5.5%. Our contributions advance efforts toward safer multilingual LLMs for all global users.

Text detoxification is a textual style transfer (TST) task where a text is paraphrased from a toxic surface form, e.g. featuring rude words, to the neutral register. Recently, text detoxification methods found their applications in various task such as detoxification of Large Language Models (LLMs) (Leong et al., 2023; He et al., 2024; Tang et al., 2023) and toxic speech combating in social networks (Deng et al., 2023; Mun et al., 2023; Agarwal et al., 2023). All these applications are extremely important to ensure safe communication in modern digital worlds. However, the previous approaches for parallel text detoxification corpora collection -- ParaDetox (Logacheva et al., 2022) and APPADIA (Atwell et al., 2022) -- were explored only in monolingual setup. In this work, we aim to extend ParaDetox pipeline to multiple languages presenting MultiParaDetox to automate parallel detoxification corpus collection for potentially any language. Then, we experiment with different text detoxification models -- from unsupervised baselines to LLMs and fine-tuned models on the presented parallel corpora -- showing the great benefit of parallel corpus presence to obtain state-of-the-art text detoxification models for any language.

Text detoxification aims to minimize the risk of language models producing toxic content. Existing detoxification methods of directly constraining the model output or further training the model on the non-toxic corpus fail to achieve a decent balance between detoxification effectiveness and generation quality. This issue stems from the neglect of constrain imposed by the context since language models are designed to generate output that closely matches the context while detoxification methods endeavor to ensure the safety of the output even if it semantically deviates from the context. In view of this, we introduce a Context-aware Model self-Detoxification~(CMD) framework that pays attention to both the context and the detoxification process, i.e., first detoxifying the context and then making the language model generate along the safe context. Specifically, CMD framework involves two phases: utilizing language models to synthesize data and applying these data for training. We also introduce a toxic contrastive loss that encourages the model generation away from the negative toxic samples. Experiments on various LLMs have verified the effectiveness of our MSD framework, which can yield the best performance compared to baselines.