title: Differential expression analysis of human endogenous retroviruses based on ENCODE RNA-seq data.
abstract: BACKGROUND
  Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which possess promoter activity and can therefore influence the expression of neighboring genes. HERV involvement in different types of cancer has already been thoroughly documented. However, so far there has been no systematic study of HERV expression patterns in a multitude of cell types in health and disease. In particular, the publication of the comprehensive ENCODE dataset has already facilitated many gene expression studies, but none so far focusing exclusively on HERVs.
  
  
  RESULTS
  We present a comprehensive differential analysis of HERV expression based on ENCODE Tier 1 and Tier 2 RNA-seq data produced by Cold Spring Harbor Laboratories and the California Institute of Technology. This analysis was conducted for individual HERV loci and for entire HERV families in twelve different cell lines, of which six correspond to the normal condition and the other six represent cancer cell types. Although the principal component analysis revealed that the two groups of cells show distinguishable expression patterns, we were not able to link these differences to one or multiple particular HERV families. Two samples exhibit expression patterns, which are not similar to the corresponding cell lines of the other producing lab. Instead they show signs of cancer formation and expression of the pluripotency marker HERVH, despite being classified as a normal cell line and a differentiated cell, respectively.
  
  
  CONCLUSIONS
  Our study demonstrates that ENCODE data are generally comparable between the different contributing labs and that the analysis of HERV elements can provide novel insights into differentiation and disease state of a cell that are easily overlooked when focusing on protein-coding genes. Our findings hint at a change in HERV expression during cancerogenesis.
authors.affiliation: Department of Genome Oriented Bioinformatics, Wissenschaftszentrum Weihenstephan, TU München, Maximus-von-Imhof-Forum 3, Freising, 85354, Germany. haase@wzw.tum.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Haase
authors.affiliation: Department of Genome Oriented Bioinformatics, Wissenschaftszentrum Weihenstephan, TU München, Maximus-von-Imhof-Forum 3, Freising, 85354, Germany. anja.moesch@mytum.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Mösch
authors.affiliation: Department of Genome Oriented Bioinformatics, Wissenschaftszentrum Weihenstephan, TU München, Maximus-von-Imhof-Forum 3, Freising, 85354, Germany. d.frishman@wzw.tum.de.|Helmholtz Center Munich - German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraße 1, Neuherberg, 85764, Germany. d.frishman@wzw.tum.de.|St Petersburg State Polytechnical University, St. Petersburg, 195251, Russia. d.frishman@wzw.tum.de.
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
mesh_terms: D002460:Cell Line; D030541:Databases, Genetic; D053595:Embryonic Stem Cells / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics*; D020869:Gene Expression Profiling; D020043:Genes, Essential / Q000235:genetics; D006801:Humans; D017423:Sequence Analysis, RNA