Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles
Shan He,
Matthew M. Gubin,
Hind Rafei,
Rafet Basar,
Merve Dede,
Xianli Jiang,
Qingnan Liang,
Yukun Tan,
Kunhee Kim,
Maura L. Gillison,
Katayoun Rezvani,
Weiyi Peng,
Cara Haymaker,
Sharia Hernandez,
Luisa M. Solis,
Vakul Mohanty,
Ken Chen
Affiliations
Shan He
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Matthew M. Gubin
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Hind Rafei
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Rafet Basar
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Merve Dede
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Xianli Jiang
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Qingnan Liang
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yukun Tan
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Kunhee Kim
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Maura L. Gillison
Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Katayoun Rezvani
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Weiyi Peng
Department of Biology and Biochemistry, The University of Houston, Houston, TX, USA
Cara Haymaker
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Sharia Hernandez
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Luisa M. Solis
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Vakul Mohanty
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
Ken Chen
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
Summary: Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated that these gene sets can be applied to refine pan-cancer immune subtypes, improve ICB response prediction and functionally annotate spatial transcriptomic data. These functional gene sets, informing diverse immune states, will advance our understanding of immunology and cancer research.
