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However, extracting meaningful phenotype-related features is challenging due to noise, batch effects, and irrelevant biological signals. To address this, we introduce Deep scSTAR (DscSTAR), a deep learning-based tool designed to enhance phenotype-associated features. DscSTAR identified HSP+ FKBP4+ T cells in CD8+ T cells, which linked to immune dysfunction and resistance to immune checkpoint blockade in non-small cell lung cancer. It has also enhanced spatial transcriptomics analysis of renal cell carcinoma, revealing interactions between cancer cells, CD8+ T cells, and tumor-associated macrophages that may promote immune suppression and affect outcomes. In hepatocellular carcinoma, it highlighted the role of S100A12+ neutrophils and cancer-associated fibroblasts in forming tumor immune barriers and potentially contributing to immunotherapy resistance. These findings demonstrate DscSTAR\u2019s capacity to model and extract phenotype-specific information, advancing our understanding of disease mechanisms and therapy resistance.<\/jats:p>","DOI":"10.1093\/bib\/bbaf160","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T19:24:16Z","timestamp":1746213856000},"source":"Crossref","is-referenced-by-count":4,"title":["Deep scSTAR: leveraging deep learning for the extraction and enhancement of phenotype-associated features from single-cell RNA sequencing and spatial transcriptomics data"],"prefix":"10.1093","volume":"26","author":[{"given":"Lianchong","family":"Gao","sequence":"first","affiliation":[{"name":"Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University , 800# Dong Chuan Road, Minhang District, Shanghai 200240 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University , Shanghai 200433 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Zou","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Biochemistry and Cell Biology , Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, , Shanghai 200031 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, , Shanghai 200031 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulan","family":"Deng","sequence":"additional","affiliation":[{"name":"Centre for Artificial Intelligence Driven Drug Discovery , Faculty of Applied Sciences, , Macao SAR ,","place":["China"]},{"name":"Macao Polytechnic University , Faculty of Applied Sciences, , Macao SAR ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery , Zhongshan Hospital, , Shanghai 200032 ,","place":["China"]},{"name":"Fudan University , Zhongshan Hospital, , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People\u2019s Hospital, School of Medicine, , Shanghai 200011 ,","place":["China"]},{"name":"Shanghai Jiao Tong University , Ninth People\u2019s Hospital, School of Medicine, , Shanghai 200011 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People\u2019s Hospital, School of Medicine, , Shanghai 200011 ,","place":["China"]},{"name":"Shanghai Jiao Tong University , Ninth People\u2019s Hospital, School of Medicine, , Shanghai 200011 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , ,","place":["China"]},{"name":"Shanghai 200127 , ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry H Y","family":"Tong","sequence":"additional","affiliation":[{"name":"Centre for Artificial Intelligence Driven Drug Discovery , Faculty of Applied Sciences, , Macao SAR ,","place":["China"]},{"name":"Macao Polytechnic University , Faculty of Applied Sciences, , Macao SAR ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Ji","sequence":"additional","affiliation":[{"name":"Molecular Pathology Center , Dept. Pathology, Zhongshan Hospital, , Shanghai 200032 ,","place":["China"]},{"name":"Fudan University , Dept. 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