Ghulam Murtaza

Tassallah Abdullahi, Ioanna Gemou, Nihal V. Nayak et al.

Biomedical knowledge graphs (KGs) encode rich, structured information critical for drug discovery tasks, but extracting meaningful insights from large-scale KGs remains challenging due to their complex structure. Existing biomedical subgraph retrieval methods are tailored for graph neural networks (GNNs), limiting compatibility with other paradigms, including large language models (LLMs). We introduce K-Paths, a model-agnostic retrieval framework that extracts structured, diverse, and biologically meaningful multi-hop paths from dense biomedical KGs. These paths enable the prediction of unobserved drug-drug and drug-disease interactions, including those involving entities not seen during training, thus supporting inductive reasoning. K-Paths is training-free and employs a diversity-aware adaptation of Yen's algorithm to extract the K shortest loopless paths between entities in a query, prioritizing biologically relevant and relationally diverse connections. These paths serve as concise, interpretable reasoning chains that can be directly integrated with LLMs or GNNs to improve generalization, accuracy, and enable explainable inference. Experiments on benchmark datasets show that K-Paths improves zero-shot reasoning across state-of-the-art LLMs. For instance, Tx-Gemma 27B improves by 19.8 and 4.0 F1 points on interaction severity prediction and drug repurposing tasks, respectively. Llama 70B achieves gains of 8.5 and 6.2 points on the same tasks. K-Paths also boosts the training efficiency of EmerGNN, a state-of-the-art GNN, by reducing the KG size by 90% while maintaining predictive performance. Beyond efficiency, K-Paths bridges the gap between KGs and LLMs, enabling scalable and explainable LLM-augmented scientific discovery. We release our code and the retrieved paths as a benchmark for inductive reasoning.

Wei Cheng, Ghulam Murtaza, Aaron Wang

Due to recent breakthroughs in state-of-the-art DNA sequencing technology, genomics data sets have become ubiquitous. The emergence of large-scale data sets provides great opportunities for better understanding of genomics, especially gene regulation. Although each cell in the human body contains the same set of DNA information, gene expression controls the functions of these cells by either turning genes on or off, known as gene expression levels. There are two important factors that control the expression level of each gene: (1) Gene regulation such as histone modifications can directly regulate gene expression. (2) Neighboring genes that are functionally related to or interact with each other that can also affect gene expression level. Previous efforts have tried to address the former using Attention-based model. However, addressing the second problem requires the incorporation of all potentially related gene information into the model. Though modern machine learning and deep learning models have been able to capture gene expression signals when applied to moderately sized data, they have struggled to recover the underlying signals of the data due to the nature of the data's higher dimensionality. To remedy this issue, we present SimpleChrome, a deep learning model that learns the latent histone modification representations of genes. The features learned from the model allow us to better understand the combinatorial effects of cross-gene interactions and direct gene regulation on the target gene expression. The results of this paper show outstanding improvements on the predictive capabilities of downstream models and greatly relaxes the need for a large data set to learn a robust, generalized neural network. These results have immediate downstream effects in epigenomics research and drug development.