Hua Xu

Rongbin Li, Wenbo Chen, Zhao Li et al.

Single-cell RNA sequencing has transformed our ability to identify diverse cell types and their transcriptomic signatures. However, annotating these signatures-especially those involving poorly characterized genes-remains a major challenge. Traditional methods, such as Gene Set Enrichment Analysis (GSEA), depend on well-curated annotations and often perform poorly in these contexts. Large Language Models (LLMs) offer a promising alternative but struggle to represent complex biological knowledge within structured ontologies. To address this, we present BRAINCELL-AID (BRAINCELL-AID: https://biodataai.uth.edu/BRAINCELL-AID), a novel multi-agent AI system that integrates free-text descriptions with ontology labels to enable more accurate and robust gene set annotation. By incorporating retrieval-augmented generation (RAG), we developed a robust agentic workflow that refines predictions using relevant PubMed literature, reducing hallucinations and enhancing interpretability. Using this workflow, we achieved correct annotations for 77% of mouse gene sets among their top predictions. Applying this approach, we annotated 5,322 brain cell clusters from the comprehensive mouse brain cell atlas generated by the BRAIN Initiative Cell Census Network, enabling novel insights into brain cell function by identifying region-specific gene co-expression patterns and inferring functional roles of gene ensembles. BRAINCELL-AID also identifies Basal Ganglia-related cell types with neurologically meaningful descriptions. Hence, we create a valuable resource to support community-driven cell type annotation.

Mingchen Li, Jiatan Huang, Jeremy Yeung et al.

Medical Large Language Models (LLMs) have demonstrated impressive performance on a wide variety of medical NLP tasks; however, there still lacks a LLM specifically designed for phenotyping identification and diagnosis in cancer domain. Moreover, these LLMs typically have several billions of parameters, making them computationally expensive for healthcare systems. Thus, in this study, we propose CancerLLM, a model with 7 billion parameters and a Mistral-style architecture, pre-trained on nearly 2.7M clinical notes and over 515K pathology reports covering 17 cancer types, followed by fine-tuning on two cancer-relevant tasks, including cancer phenotypes extraction and cancer diagnosis generation. Our evaluation demonstrated that the CancerLLM achieves state-of-the-art results with F1 score of 91.78% on phenotyping extraction and 86.81% on disganois generation. It outperformed existing LLMs, with an average F1 score improvement of 9.23%. Additionally, the CancerLLM demonstrated its efficiency on time and GPU usage, and robustness comparing with other LLMs. We demonstrated that CancerLLM can potentially provide an effective and robust solution to advance clinical research and practice in cancer domain

Sijia Liu, Andrew Wen, Liwei Wang et al.

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, interpretability, and usability. In this study, we proposed an open natural language processing development framework. We evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The corpora were derived from texts from three different institutions (Mayo Clinic, University of Kentucky, University of Minnesota). The gold standard annotations were tested with a single institution's (Mayo) ruleset. This resulted in performances of 0.876, 0.706, and 0.694 in F-scores for Mayo, Minnesota, and Kentucky test datasets, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study and adoption. Although we use COVID-19 as a use case in this effort, our framework is general enough to be applied to other domains of interest in clinical NLP.