TimiGP: Inferring cell-cell interactions and prognostic associations in the tumor immune microenvironment through gene pairs

Chenyang Li; Baoyi Zhang; Evelien Schaafsma; Alexandre Reuben; Linghua Wang; Mary Jo Turk; Jianjun Zhang; Chao Cheng

doi:10.1016/j.xcrm.2023.101121

TimiGP: Inferring cell-cell interactions and prognostic associations in the tumor immune microenvironment through gene pairs

Cell Rep Med. 2023 Jul 18;4(7):101121. doi: 10.1016/j.xcrm.2023.101121.

Authors

Chenyang Li¹, Baoyi Zhang², Evelien Schaafsma³, Alexandre Reuben⁴, Linghua Wang¹, Mary Jo Turk⁵, Jianjun Zhang⁶, Chao Cheng⁷

Affiliations

¹ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center UTHealth Houston, Houston, TX 77030, USA.
² Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77030, USA.
³ Department of Microbiology and Immunology, Dartmouth College, Hanover, NH 03755, USA.
⁴ Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center UTHealth Houston, Houston, TX 77030, USA; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁵ Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
⁶ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center UTHealth Houston, Houston, TX 77030, USA; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Lung Cancer Genomics Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Lung Cancer Interception Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jzhang20@mdanderson.org.
⁷ Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; The Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: chao.cheng@bcm.edu.

Abstract

Determining the prognostic association of different immune cell types in the tumor microenvironment is critical for understanding cancer biology and developing new therapeutic strategies. However, this is challenging in certain cancer types, where the abundance of different immune subsets is highly correlated. In this study, we develop a computational method named TimiGP to overcome this challenge. Based on bulk gene expression and survival data, TimiGP infers cell-cell interactions that reveal the association between immune cell relative abundance and prognosis. As demonstrated in metastatic melanoma, TimiGP prioritizes immune cells critical in prognosis based on the identified cell-cell interactions. Highly consistent results are obtained by TimiGP when applied to seven independent melanoma datasets and when different cell-type marker sets are used as inputs. Additionally, TimiGP can leverage single-cell RNA sequencing data to delineate the tumor immune microenvironment at high resolutions across a wide range of cancer types.

Keywords: cell-cell interaction network; prognostic associations of immune cells; prognostic model; transcriptome-based method; tumor immune microenvironment.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Communication / genetics
Humans
Melanoma* / genetics
Prognosis
Tumor Microenvironment* / genetics

Abstract

Publication types

MeSH terms

Grants and funding