Hunting complex differential gene interaction patterns across molecular contexts.
Heterogeneity in genetic networks across different signaling molecular contexts can suggest molecular regulatory mechanisms. Here we describe a comparative chi-square analysis (CPχ(2)) method, considerably more flexible and effective than other alternatives, to screen large gene expression data sets for conserved and differential interactions. CPχ(2) decomposes interactions across conditions to assess homogeneity and heterogeneity. Theoretically, we prove an asymptotic chi-square null distribution for the interaction heterogeneity statistic. Empirically, on synthetic yeast cell cycle data, CPχ(2) achieved much higher statistical power in detecting differential networks than alternative approaches. We applied CPχ(2) to Drosophila melanogaster wing gene expression arrays collected under normal conditions, and conditions with overexpressed E2F and Cabut, two transcription factor complexes that promote ectopic cell cycling. The resulting differential networks suggest a mechanism by which E2F and Cabut regulate distinct gene interactions, while still sharing a small core network. Thus, CPχ(2) is sensitive in detecting network rewiring, useful in comparing related biological systems.
Department of Computer Science, New Mexico State University, Las Cruces, NM 88003, USA, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA and German Cancer Research Center (DKFZ)-Center for Molecular Biology Heidelberg (ZMBH) Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Mingzhou
M
Song
Yang
Y
Zhang
Alexia J
AJ
Katzaroff
Bruce A
BA
Edgar
Laura
L
Buttitta
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016009:Chi-Square Distribution; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics; D050684:E2F Transcription Factors / Q000502:physiology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D014157:Transcription Factors / Q000502:physiology; D015003:Yeasts / Q000235:genetics
C506602:Cbt protein, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; D014157:Transcription Factors