title: Uncovering the liver's role in immunity through RNA co-expression networks.
abstract: Gene co-expression analysis has proven to be a powerful tool for ascertaining the organization of gene products into networks that are important for organ function. An organ, such as the liver, engages in a multitude of functions important for the survival of humans, rats, and other animals; these liver functions include energy metabolism, metabolism of xenobiotics, immune system function, and hormonal homeostasis. With the availability of organ-specific transcriptomes, we can now examine the role of RNA transcripts (both protein-coding and non-coding) in these functions. A systems genetic approach for identifying and characterizing liver gene networks within a recombinant inbred panel of rats was used to identify genetically regulated transcriptional networks (modules). For these modules, biological consensus was found between functional enrichment analysis and publicly available phenotypic quantitative trait loci (QTL). In particular, the biological function of two liver modules could be linked to immune response. The eigengene QTLs for these co-expression modules were located at genomic regions coincident with highly significant phenotypic QTLs; these phenotypes were related to rheumatoid arthritis, food preference, and basal corticosterone levels in rats. Our analysis illustrates that genetically and biologically driven RNA-based networks, such as the ones identified as part of this research, provide insight into the genetic influences on organ functions. These networks can pinpoint phenotypes that manifest through the interaction of many organs/tissues and can identify unannotated or under-annotated RNA transcripts that play a role in these phenotypes.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, 80045, USA.|Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO, 80045, USA.
authors.forename: Kylie K
authors.initials: KK
authors.lastname: Harrall
authors.affiliation: Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO, 80045, USA.
authors.forename: Katerina J
authors.initials: KJ
authors.lastname: Kechris
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, 80045, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Tabakoff
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hoffman
authors.affiliation: Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO, 80918, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hines
authors.affiliation: Department of Pathology, Southern California Research Center for ALPD and Cirrhosis, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90089, USA.|Department of Veterans Affairs, Great Los Angeles Healthcare System, Los Angeles, CA, 90089, USA.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Morton
authors.initials: M
authors.lastname: Printz
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, 80045, USA. laura.saba@ucdenver.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Saba
mesh_terms: D000818:Animals; D005260:Female; D063990:Gene Ontology; D007107:Immune System / Q000378:metabolism; D015810:Linkage Disequilibrium; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D008126:Lod Score; D008297:Male; D040641:Quantitative Trait Loci; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D011918:Rats, Inbred SHR; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D012313:RNA