Elucidating Immune-Related Gene Transcriptional Programs via Factorization of Large-Scale RNA-Profiles

Authors

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

Publication Date

6-21-2024

Journal

Cell Press

Abstract

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.

Keywords

Bioinformatics, Cancer, Expression study, Immunity, Molecular network, Transcriptomics

Comments

Supplementary Materials

Data Availability Statement