InDePTH: detection of hub genes for developing gene expression networks under anticancer drug treatment

Oncotarget
Masaru KoidoAkihiro Tomida

Abstract

It has been difficult to elucidate the structure of gene regulatory networks under anticancer drug treatment. Here, we developed an algorithm to highlight the hub genes that play a major role in creating the upstream and downstream relationships within a given set of differentially expressed genes. The directionality of the relationships between genes was defined using information from comprehensive collections of transcriptome profiles after gene knockdown and overexpression. As expected, among the drug-perturbed genes, our algorithm tended to derive plausible hub genes, such as transcription factors. Our validation experiments successfully showed the anticipated activity of certain hub gene in establishing the gene regulatory network that was associated with cell growth inhibition. Notably, giving such top priority to the hub gene was not achieved by ranking fold change in expression and by the conventional gene set enrichment analysis of drug-induced transcriptome data. Thus, our data-driven approach can facilitate to understand drug-induced gene regulatory networks for finding potential functional genes.

References

May 14, 1982·JAMA : the Journal of the American Medical Association·F E HarrellR A Rosati
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Jan 25, 2002·Genes, Chromosomes & Cancer·Sukvarsha MehraR S K Chaganti
Feb 13, 2004·Bioinformatics·Laurent GautierRafael A Irizarry
Jan 1, 1950·Cancer·W J YOUDEN
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 19, 2006·Nature Reviews. Genetics·Lars Juhl JensenPeer Bork
Mar 11, 2006·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·S-Q LiuH-l Chen
Dec 23, 2006·Nature Reviews. Cancer·Justin Lamb
Sep 20, 2008·Toxicology Letters·Hiroyoshi ToyoshibaAkira Horinouchi
Mar 19, 2011·BMC Bioinformatics·Xavier RobinMarkus Müller
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ka Yee YeungAdrian E Raftery
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Jul 11, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sally E TrabuccoHong Zhang
Nov 25, 2014·Nature Biotechnology·Mukesh BansalUNKNOWN NCI-DREAM Community
Dec 11, 2014·BMC Bioinformatics·Aravind VenkatesanMartin Kuiper
Sep 26, 2015·PLoS Computational Biology·Gang LiK Vijay-Shanker
Jan 16, 2016·Cell Systems·Arthur LiberzonPablo Tamayo
Feb 14, 2016·Bioinformatics·Yifei ChenXiaohui Xie
Jul 26, 2017·Nature Communications·Erin C BushPeter A Sims
Aug 31, 2017·European Journal of Human Genetics : EJHG·Fabian BaertlingLeo G J Nijtmans
Oct 13, 2017·Nature·UNKNOWN GTEx ConsortiumStephen B Montgomery

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Citations

Jun 18, 2021·Plant Science : an International Journal of Experimental Plant Biology·Yongjun HeHuoying Chen
Aug 18, 2021·Biochemical and Biophysical Research Communications·Yukie IwaoAkihiro Tomida
Nov 2, 2020·Biophysical Journal·Muying WangJason E Shoemaker

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Methods Mentioned

BETA
transfection

Software Mentioned

R
R script
Affymetrix Microarray Suite
db
GSEA
Gene Set Enrichment Analysis ( GSEA )
R package affy
Library of Integrated Network - Based Cellular Signatures ( LI...
R package pROC
hgu133plus2

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