title: Evolutionary-conserved gene expression response profiles across mammalian tissues.
abstract: Gene expression responses are complex and frequently involve the actions of many genes to effect coordinated patterns. We hypothesized these coordinated responses are evolutionarily conserved and used a comparison of human and mouse gene expression profiles to identify the most prominent conserved features across a set of normal mammalian tissues. Based on data from multiple studies across multiple tissues in human and mouse, 13 gene expression modes across multiple tissues were identified in each of these species using principal component analysis. Strikingly, 1-to-1 pairing of human and mouse modes was observed in 12 out of 13 modes obtained from the two species independently. These paired modes define evolutionarily conserved gene expression response modes (CGEMs). Notably, in this study we were able to extract biological responses that are not overwhelmed by laboratory-to-laboratory or species-to-species variation. Of the variation in our gene expression dataset, 84% can be explained using these CGEMs. Functional annotation was performed using Gene Ontology, pathway, and transcription factor binding site over representation. Our conclusion is that we found an unbiased way of obtaining conserved gene response modes that accounts for a considerable portion of gene expression variation in a given dataset, as well as validates the conservation of major gene expression response modes across the mammals.
authors.affiliation: Bioinformatics Program, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Blackwell
authors.forename: Damian
authors.initials: D
authors.lastname: Fermin
authors.forename: Rajasree
authors.initials: R
authors.lastname: Menon
authors.forename: Yili
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Angel W
authors.initials: AW
authors.lastname: Lee
authors.forename: David J
authors.initials: DJ
authors.lastname: States
mesh_terms: D000818:Animals; D001665:Binding Sites; D016000:Cluster Analysis; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors