Investigation of the Genome-Wide Genetic and Epigenetic Networks for Drug Discovery Based on Systems Biology Approaches in Colorectal Cancer.

Abstract:

:Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. The mechanisms leading to the progression of CRC are involved in both genetic and epigenetic regulations. In this study, we applied systems biology methods to identify potential biomarkers and conduct drug discovery in a computational approach. Using big database mining, we constructed a candidate protein-protein interaction network and a candidate gene regulatory network, combining them into a genome-wide genetic and epigenetic network (GWGEN). With the assistance of system identification and model selection approaches, we obtain real GWGENs for early-stage, mid-stage, and late-stage CRC. Subsequently, we extracted core GWGENs for each stage of CRC from their real GWGENs through a principal network projection method, and projected them to the Kyoto Encyclopedia of Genes and Genomes pathways for further analysis. Finally, we compared these core pathways resulting in different molecular mechanisms in each stage of CRC and identified carcinogenic biomarkers for the design of multiple-molecule drugs to prevent the progression of CRC. Based on the identified gene expression signatures, we suggested potential compounds combined with known CRC drugs to prevent the progression of CRC with querying Connectivity Map (CMap).

journal_name

Front Genet

journal_title

Frontiers in genetics

authors

Yeh SJ,Chen SW,Chen BS

doi

10.3389/fgene.2020.00117

subject

Has Abstract

pub_date

2020-03-06 00:00:00

pages

117

issn

1664-8021

journal_volume

11

pub_type

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