Multi-Omics Data Analysis Uncovers Molecular Networks and Gene Regulators for Metabolic Biomarkers

Year: 2021

Type: article

Abstract: The insulin-like growth factors (IGFs)/insulin resistance (IR) axis is the major metabolic hormonal pathway mediating the biologic mechanism of several complex human diseases, including type 2 diabetes (T2DM) and cancers. The genomewide association study (GWAS)-based approach has neither fully characterized the phenotype variation nor provided a comprehensive understanding of the regulatory biologic mechanisms. We applied systematic genomics to integrate our previous GWAS data for IGF-I and IR with multi-omics datasets, e.g., whole-blood expression quantitative loci, molecular pathways, and gene network, to capture the full range of genetic functionalities associated with IGF-I/IR and key drivers (KDs) in gene-regulatory networks. We identified both shared (e.g., T2DM, lipid metabolism, and estimated glomerular filtration signaling) and IR-specific (e.g., mechanistic target of rapamycin, phosphoinositide 3-kinases, and erb-b2 receptor tyrosine kinase 4 signaling) molecular biologic processes of IGF-I/IR axis regulation. Next, by using tissue-specific gene–gene interaction networks, we identified both well-established (e.g., IRS1 and IGF1R) and novel (e.g., AKT1, HRAS, and JAK1) KDs in the IGF-I/IR-associated subnetworks. Our results, if validated in additional genomic studies, may provide robust, comprehensive insights into the mechanisms of IGF-I/IR regulation and highlight potential novel genetic targets as preventive and therapeutic strategies for the associated diseases, e.g., T2DM and cancers.

Source: Biomolecules

DOI: 10.3390/biom11030406

Author: Su Yon Jung

Institutions: University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center

Language: English

Topic: Bioinformatics and Genomic Networks

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,160

Funders: U.S. Department of Health and Human Services, Brigham and Women's Hospital, Ohio State University, Wake Forest University, University of Pittsburgh, MedStar Health Research Institute, National Institutes of Health, University of California, Los Angeles, University at Buffalo, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Nursing Research, NIH Clinical Center, Institute for Digital Research and Education, University of California, Los Angeles

OpenAlex ID: W3134288128