Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival

Simhal, Anish K, Maclachlan, Kylee H, Elkin, Rena, Zhu, Jiening, Norton, Larry, Deasy, Joseph O, Oh, Jung Hun, Usmani, Saad Z, Tannenbaum, Allen (November 2023) Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival. Blood Cancer Journal, 13 (1). p. 175. ISSN 2044-5385

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Abstract

The plasma cell cancer multiple myeloma (MM) varies significantly in genomic characteristics, response to therapy, and long-term prognosis. To investigate global interactions in MM, we combined a known protein interaction network with a large clinically annotated MM dataset. We hypothesized that an unbiased network analysis method based on large-scale similarities in gene expression, copy number aberration, and protein interactions may provide novel biological insights. Applying a novel measure of network robustness, Ollivier-Ricci Curvature, we examined patterns in the RNA-Seq gene expression and CNA data and how they relate to clinical outcomes. Hierarchical clustering using ORC differentiated high-risk subtypes with low progression free survival. Differential gene expression analysis defined 118 genes with significantly aberrant expression. These genes, while not previously associated with MM, were associated with DNA repair, apoptosis, and the immune system. Univariate analysis identified 8/118 to be prognostic genes; all associated with the immune system. A network topology analysis identified both hub and bridge genes which connect known genes of biological significance of MM. Taken together, gene interaction network analysis in MM uses a novel method of global assessment to demonstrate complex immune dysregulation associated with shorter survival.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > analysis and processing bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene network bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function organs, tissues, organelles, cell types and functions diseases & disorders > cancer > prognosis
CSHL Authors:	Norton, Larry
Communities:	CSHL labs > Wigler lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	30 November 2023
Date Deposited:	20 Dec 2023 18:58
Last Modified:	10 Jan 2024 21:13
PMCID:	PMC10687027
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41335

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