Feature attribution methods, which explain an individual prediction made by a model as a sum of attributions for each input feature, are an essential tool for understanding the behavior of complex deep learning models. However, ensuring that models produce meaningful explanations, rather than ones that rely on noise, is not straightforward. Exacerbating this problem is the fact that attribution methods do not provide insight as to why features are assigned their attribution values, leading to explanations that are difficult to interpret. In real-world problems we often have sets of additional information for each feature that are predictive of that feature's importance to the task at hand. Here, we propose the deep attribution prior (DAPr) framework to exploit such information to overcome the limitations of attribution methods. Our framework jointly learns a relationship between prior information and feature importance, as well as biases models to have explanations that rely on features predicted to be important. We find that our framework both results in networks that generalize better to out of sample data and admits new methods for interpreting model behavior.

Revolutionizing drug discovery demands more than just understanding molecular interactions - it requires generative models that can design novel ligands tailored to specific biological targets. While chemical Language Models (cLMs) have made strides in learning molecular properties, most fail to incorporate target-specific insights, restricting their ability to drive de-novo ligand generation. Chem42, a cutting-edge family of generative chemical Language Models, is designed to bridge this gap. By integrating atomic-level interactions with multimodal inputs from Prot42, a complementary protein Language Model, Chem42 achieves a sophisticated cross-modal representation of molecular structures, interactions, and binding patterns. This innovative framework enables the creation of structurally valid, synthetically accessible ligands with enhanced target specificity. Evaluations across diverse protein targets confirm that Chem42 surpasses existing approaches in chemical validity, target-aware design, and predicted binding affinity. By reducing the search space of viable drug candidates, Chem42 could accelerate the drug discovery pipeline, offering a powerful generative AI tool for precision medicine. Our Chem42 models set a new benchmark in molecule property prediction, conditional molecule generation, and target-aware ligand design. The models are publicly available at huggingface.co/inceptionai.

The applications of large language models (LLMs) in various biological domains have been explored recently, but their reasoning ability in complex biological systems, such as pathways, remains underexplored, which is crucial for predicting biological phenomena, formulating hypotheses, and designing experiments. This work explores the potential of LLMs in pathway reasoning. We introduce BioMaze, a dataset with 5.1K complex pathway problems derived from real research, covering various biological contexts including natural dynamic changes, disturbances, additional intervention conditions, and multi-scale research targets. Our evaluation of methods such as CoT and graph-augmented reasoning, shows that LLMs struggle with pathway reasoning, especially in perturbed systems. To address this, we propose PathSeeker, an LLM agent that enhances reasoning through interactive subgraph-based navigation, enabling a more effective approach to handling the complexities of biological systems in a scientifically aligned manner. The dataset and code are available at https://github.com/zhao-ht/BioMaze.

Genes, proteins and other biological entities influence one another via causal molecular networks. Causal relationships in such networks are mediated by complex and diverse mechanisms, through latent variables, and are often specific to cellular context. It remains challenging to characterise such networks in practice. Here, we present a novel framework to evaluate large language models (LLMs) for zero-shot inference of causal relationships in biology. In particular, we systematically evaluate causal claims obtained from an LLM using real-world interventional data. This is done over one hundred variables and thousands of causal hypotheses. Furthermore, we consider several prompting and retrieval-augmentation strategies, including large, and potentially conflicting, collections of scientific articles. Our results show that with tailored augmentation and prompting, even relatively small LLMs can capture meaningful aspects of causal structure in biological systems. This supports the notion that LLMs could act as orchestration tools in biological discovery, by helping to distil current knowledge in ways amenable to downstream analysis. Our approach to assessing LLMs with respect to experimental data is relevant for a broad range of problems at the intersection of causal learning, LLMs and scientific discovery.

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

The complexities inherent to leukemia, multifaceted cancer affecting white blood cells, pose considerable diagnostic and treatment challenges, primarily due to reliance on laborious morphological analyses and expert judgment that are susceptible to errors. Addressing these challenges, this study presents a refined, comprehensive strategy leveraging advanced deep-learning techniques for the classification of leukemia subtypes. We commence by developing a hierarchical label taxonomy, paving the way for differentiating between various subtypes of leukemia. The research further introduces a novel hierarchical approach inspired by clinical procedures capable of accurately classifying diverse types of leukemia alongside reactive and healthy cells. An integral part of this study involves a meticulous examination of the performance of Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs) as classifiers. The proposed method exhibits an impressive success rate, achieving approximately 90\% accuracy across all leukemia subtypes, as substantiated by our experimental results. A visual representation of the experimental findings is provided to enhance the model's explainability and aid in understanding the classification process.

Thousands of individuals succumb annually to leukemia alone. As artificial intelligence-driven technologies continue to evolve and advance, the question of their applicability and reliability remains unresolved. This study aims to utilize image processing and deep learning methodologies to achieve state-of-the-art results for the detection of Acute Lymphoblastic Leukemia (ALL) using data that best represents real-world scenarios. ALL is one of several types of blood cancer, and it is an aggressive form of leukemia. In this investigation, we examine the most recent advancements in ALL detection, as well as the latest iteration of the YOLO series and its performance. We address the question of whether white blood cells are malignant or benign. Additionally, the proposed models can identify different ALL stages, including early stages. Furthermore, these models can detect hematogones despite their frequent misclassification as ALL. By utilizing advanced deep learning models, namely, YOLOv8, YOLOv11, ResNet50 and Inception-ResNet-v2, the study achieves accuracy rates as high as 99.7%, demonstrating the effectiveness of these algorithms across multiple datasets and various real-world situations.

The examination of blood samples at a microscopic level plays a fundamental role in clinical diagnostics. For instance, an in-depth study of White Blood Cells (WBCs), a crucial component of our blood, is essential for diagnosing blood-related diseases such as leukemia and anemia. While multiple datasets containing WBC images have been proposed, they mostly focus on cell categorization, often lacking the necessary morphological details to explain such categorizations, despite the importance of explainable artificial intelligence (XAI) in medical domains. This paper seeks to address this limitation by introducing comprehensive annotations for WBC images. Through collaboration with pathologists, a thorough literature review, and manual inspection of microscopic images, we have identified 11 morphological attributes associated with the cell and its components (nucleus, cytoplasm, and granules). We then annotated ten thousand WBC images with these attributes, resulting in 113k labels (11 attributes x 10.3k images). Annotating at this level of detail and scale is unprecedented, offering unique value to AI in pathology. Moreover, we conduct experiments to predict these attributes from cell images, and also demonstrate specific applications that can benefit from our detailed annotations. Overall, our dataset paves the way for interpreting WBC recognition models, further advancing XAI in the fields of pathology and hematology.