title: Analysis of genome-wide RNA-sequencing data suggests age of the CEPH/Utah (CEU) lymphoblastoid cell lines systematically biases gene expression profiles.
abstract: In human, Lymphoblastoid cell lines (LCLs) from the CEPH/CEU (Centre d'Etude du Polymorphisme Humain - Utah) family resource have been extensively used for examining the genetics of gene expression levels. However, we noted that CEU/CEPH cell lines were collected and transformed approximately thirty years ago, much earlier than the other cell lines from the pertaining individuals, which we suspected could potentially affect gene expression, data analysis and results interpretation. In this study, by analyzing RNA sequencing data of CEU and the other three European populations as well as an African population, we systematically examined and evaluated the potential confounding effect of LCL age on gene expression levels and patterns. Our results indicated that gene expression profiles of CEU samples have been biased by the older age of CEU cell lines. Interestingly, most of CEU-specific expressions are associated with functions related to cell proliferation, which are more likely due to older age of cell lines than intrinsic characters of the population. We suggested the results be carefully explained when CEU LCLs are used for transcriptomic data analysis in future studies.
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max-Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max-Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max-Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Lu
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max-Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
mesh_terms: D002460:Cell Line; D030541:Databases, Genetic; D005828:Genetics, Population; D015894:Genome, Human; D060005:Genotyping Techniques; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D017423:Sequence Analysis, RNA / Q000379:methods*; D059467:Transcriptome