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Phenotype-driven gene prioritization is a critical process in the diagnosis of rare genetic disorders for identifying and ranking potential disease-causing genes based on observed physical traits or phenotypes. While traditional approaches…

Quantitative Methods · Quantitative Biology 2024-04-04 Junyoung Kim , Jingye Yang , Kai Wang , Chunhua Weng , Cong Liu

The intricate relationship between genetic variation and human diseases has been a focal point of medical research, evidenced by the identification of risk genes regarding specific diseases. The advent of advanced genome sequencing…

Quantitative Methods · Quantitative Biology 2024-01-19 Jiayu Chang , Shiyu Wang , Chen Ling , Zhaohui Qin , Liang Zhao

Background: Several studies show that large language models (LLMs) struggle with phenotype-driven gene prioritization for rare diseases. These studies typically use Human Phenotype Ontology (HPO) terms to prompt foundation models like GPT…

Computation and Language · Computer Science 2026-02-19 Zhanliang Wang , Da Wu , Quan Nguyen , Kai Wang

Effective prioritization of issue reports in software engineering helps to optimize resource allocation and information recovery. However, manual issue classification is laborious and lacks scalability. As an alternative, many open source…

Software Engineering · Computer Science 2025-06-03 Gabriel Aracena , Kyle Luster , Fabio Santos , Igor Steinmacher , Marco A. Gerosa

High-throughput phenotyping, the automated mapping of patient signs and symptoms to standardized ontology concepts, is essential to gaining value from electronic health records (EHR) in the support of precision medicine. Despite…

Artificial Intelligence · Computer Science 2024-06-24 Syed I. Munzir , Daniel B. Hier , Chelsea Oommen , Michael D. Carrithers

Rare disease diagnosis requires matching variant-bearing genes to complex patient phenotypes across large and heterogeneous evidence sources. This process remains time-intensive in current clinical interpretation pipelines. To overcome…

Genomics · Quantitative Biology 2026-03-09 Jaeyeon Lee , Lin Yao , Hyun-Hwan Jeong , Zhandong Liu

Recent advances in artificial intelligence, particularly large language models LLMs, have shown promising capabilities in transforming rare disease research. This survey paper explores the integration of LLMs in the analysis of rare…

Computation and Language · Computer Science 2025-05-26 Valentina Carbonari , Pierangelo Veltri , Pietro Hiram Guzzi

Rare diseases pose significant challenges in diagnosis and treatment due to their low prevalence and heterogeneous clinical presentations. Unstructured clinical notes contain valuable information for identifying rare diseases, but manual…

Computation and Language · Computer Science 2024-11-12 Jinge Wu , Hang Dong , Zexi Li , Haowei Wang , Runci Li , Arijit Patra , Chengliang Dai , Waqar Ali , Phil Scordis , Honghan Wu

In practice, clinicians achieve a diagnosis by following a sequence of steps, such as laboratory exams, observations, or imaging. The pathways to reach diagnosis decisions are documented by guidelines authored by expert organizations, which…

Computation and Language · Computer Science 2024-09-25 Elisa Castagnari , Lillian Muyama , Adrien Coulet

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face…

Pre-trained large language models(LLMs) have attracted increasing attention in biomedical domains due to their success in natural language processing. However, the complex traits and heterogeneity of multi-sources genomics data pose…

Computation and Language · Computer Science 2025-11-25 Yanjun Lyu , Zihao Wu , Lu Zhang , Jing Zhang , Yiwei Li , Wei Ruan , Zhengliang Liu , Zeyu Zhang , Xiang Li , Rongjie Liu , Chao Huang , Wentao Li , Tianming Liu , Dajiang Zhu

Large language models (LLMs) have demonstrated capabilities across diverse domains, yet their performance on rare disease diagnosis from narrative medical cases remains underexplored. We introduce a novel dataset of 176 symptom-diagnosis…

Computation and Language · Computer Science 2025-11-17 Arsh Gupta , Ajay Narayanan Sridhar , Bonam Mingole , Amulya Yadav

Identifying disease phenotypes from electronic health records (EHRs) is critical for numerous secondary uses. Manually encoding physician knowledge into rules is particularly challenging for rare diseases due to inadequate EHR coding,…

Identification of causal genes and pathways is a critical step for understanding the genetic underpinnings of rare diseases. We propose novel approaches to gene prioritization and pathway identification using DNA language model, graph…

Quantitative Methods · Quantitative Biology 2024-11-12 Ali Saadat , Jacques Fellay

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical…

Computation and Language · Computer Science 2024-07-08 Xuanzhong Chen , Xiaohao Mao , Qihan Guo , Lun Wang , Shuyang Zhang , Ting Chen

Named Entity Recognition (NER) in the rare disease domain poses unique challenges due to limited labeled data, semantic ambiguity between entity types, and long-tail distributions. In this study, we evaluate the capabilities of GPT-4o for…

Computation and Language · Computer Science 2025-12-30 Nan Miles Xi , Yu Deng , Lin Wang

Large language models (LLMs) constitute a breakthrough state-of-the-art Artificial Intelligence technology which is rapidly evolving and promises to aid in medical diagnosis. However, the correctness and the accuracy of their returns has…

Computation and Language · Computer Science 2024-02-07 Dimitrios P. Panagoulias , Maria Virvou , George A. Tsihrintzis

Large Language Models (LLMs) show promise in biomedicine but lack true causal understanding, relying instead on correlations. This paper envisions causal LLM agents that integrate multimodal data (text, images, genomics, etc.) and perform…

Artificial Intelligence · Computer Science 2025-05-23 Adib Bazgir , Amir Habibdoust Lafmajani , Yuwen Zhang

Large Language models (LLMs), such as ChatGPT, have gained popularity in recent years with the advancement of Natural Language Processing (NLP), with use cases spanning many disciplines and daily lives as well. LLMs inherit explicit and…

Computation and Language · Computer Science 2025-12-01 Fatima Kazi

Identifying disease-associated genes enables the development of precision medicine and the understanding of biological processes. Genome-wide association studies (GWAS), gene expression data, biological pathway analysis, and protein network…

Genomics · Quantitative Biology 2026-03-10 Muhammad Muneeb , David B. Ascher , YooChan Myung
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