Porcine tissue-specific regulatory networks derived from meta-analysis of the transcriptome

PLoS One. 2012;7(9):e46159. doi: 10.1371/journal.pone.0046159. Epub 2012 Sep 26.

Abstract

The processes that drive tissue identity and differentiation remain unclear for most tissue types. So are the gene networks and transcription factors (TF) responsible for the differential structure and function of each particular tissue, and this is particularly true for non model species with incomplete genomic resources. To better understand the regulation of genes responsible for tissue identity in pigs, we have inferred regulatory networks from a meta-analysis of 20 gene expression studies spanning 480 Porcine Affymetrix chips for 134 experimental conditions on 27 distinct tissues. We developed a mixed-model normalization approach with a covariance structure that accommodated the disparity in the origin of the individual studies, and obtained the normalized expression of 12,320 genes across the 27 tissues. Using this resource, we constructed a network, based on the co-expression patterns of 1,072 TF and 1,232 tissue specific genes. The resulting network is consistent with the known biology of tissue development. Within the network, genes clustered by tissue and tissues clustered by site of embryonic origin. These clusters were significantly enriched for genes annotated in key relevant biological processes and confirm gene functions and interactions from the literature. We implemented a Regulatory Impact Factor (RIF) metric to identify the key regulators in skeletal muscle and tissues from the central nervous systems. The normalization of the meta-analysis, the inference of the gene co-expression network and the RIF metric, operated synergistically towards a successful search for tissue-specific regulators. Novel among these findings are evidence suggesting a novel key role of ERCC3 as a muscle regulator. Together, our results recapitulate the known biology behind tissue specificity and provide new valuable insights in a less studied but valuable model species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Swine
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptome / genetics
  • Transcriptome / physiology*

Substances

  • DNA-Binding Proteins
  • Transcription Factors

Grants and funding

The authors acknowledge the assistance of the CSIRO Transformational Biology Capability Platform. D. Pérez-Montarelo was funded by an FPI PhD grant from the Spanish Ministerio de Ciencia e Innovación (BES-2009-025417). Y. Ramayo-Caldas was funded by an FPU PhD grant from the Spanish Ministerio de Educación (AP2008-01450). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.