title: The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.
abstract: The concordance of RNA-sequencing (RNA-seq) with microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed using a range of chemical treatment conditions. Here we use a comprehensive study design to generate Illumina RNA-seq and Affymetrix microarray data from the same liver samples of rats exposed in triplicate to varying degrees of perturbation by 27 chemicals representing multiple modes of action (MOAs). The cross-platform concordance in terms of differentially expressed genes (DEGs) or enriched pathways is linearly correlated with treatment effect size (R(2)0.8). Furthermore, the concordance is also affected by transcript abundance and biological complexity of the MOA. RNA-seq outperforms microarray (93% versus 75%) in DEG verification as assessed by quantitative PCR, with the gain mainly due to its improved accuracy for low-abundance transcripts. Nonetheless, classifiers to predict MOAs perform similarly when developed using data from either platform. Therefore, the endpoint studied and its biological complexity, transcript abundance and the genomic application are important factors in transcriptomic research and for clinical and regulatory decision making.
authors.affiliation: 1] Center for Genomics and Division of Microbiology &Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA. [2].
authors.forename: Charles
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA. [2].
authors.forename: Binsheng
authors.initials: B
authors.lastname: Gong
authors.affiliation: 1] Microarray and Genome Informatics Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. [2] Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. [3].
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Bushel
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Thierry-Mieg
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Thierry-Mieg
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Office of Scientific Coordination, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Huixiao
authors.initials: H
authors.lastname: Hong
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Meehan
authors.affiliation: Functional Genomics Core, Department of Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Li
authors.affiliation: Functional Genomics Core, Department of Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Functional Genomics Core, Department of Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Li
authors.affiliation: Chair of Bioinformatics Research Group, Boku University Vienna, Vienna, Austria.
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Łabaj
authors.affiliation: 1] Chair of Bioinformatics Research Group, Boku University Vienna, Vienna, Austria. [2] University of Warwick, Coventry, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Kreil
authors.affiliation: CMINDS Research Center, Department of Electrical and Computer Engineering, Francis College of Engineering, University of Massachusetts, Lowell, Massachusetts, USA.
authors.forename: Dalila
authors.initials: D
authors.lastname: Megherbi
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
authors.forename: Stan
authors.initials: S
authors.lastname: Gaj
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
authors.forename: Florian
authors.initials: F
authors.lastname: Caiment
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Delft
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleinjans
authors.affiliation: Australian Genome Research Facility Ltd., The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherer
authors.affiliation: AbbVie, Inc., North Chicago, Illinois, USA.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Devanarayan
authors.affiliation: Research Informatics and Statistics, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Research Informatics and Statistics, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Research Informatics and Statistics, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Qian
authors.affiliation: Thomson Reuters, IP &Science, Carlsbad, California, USA.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Lancashire
authors.affiliation: Thomson Reuters, IP &Science, Carlsbad, California, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bessarabova
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Science, Moscow, Russia.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.affiliation: Fondazione Bruno Kessler, Trento, Italy.
authors.forename: Cesare
authors.identifier: 0000000253843605
authors.initials: C
authors.lastname: Furlanello
authors.affiliation: Fondazione Bruno Kessler, Trento, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chierici
authors.affiliation: 1] Fondazione Bruno Kessler, Trento, Italy. [2] Computational Biology Department, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Albanese
authors.affiliation: Fondazione Bruno Kessler, Trento, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Jurman
authors.affiliation: 1] Fondazione Bruno Kessler, Trento, Italy. [2] Computational Biology Department, Research and Innovation Centre, Fondazione Edmund Mach (FEM), San Michele all'Adige, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Riccadonna
authors.affiliation: Fondazione Bruno Kessler, Trento, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Filosi
authors.affiliation: Fondazione Bruno Kessler, Trento, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Visintainer
authors.affiliation: Bioinformatics core, Department of Pathology, University of North Dakota, Grand Forks, North Dakota, USA.
authors.forename: Ke K
authors.initials: KK
authors.lastname: Zhang
authors.affiliation: 1] Microarray and Genome Informatics Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. [2] Kelly Government Solutions, Inc., Durham, North Carolina, USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Li
authors.affiliation: Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Jui-Hua
authors.initials: JH
authors.lastname: Hsieh
authors.affiliation: SRA International, Durham, North Carolina, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Svoboda
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Fuscoe
authors.affiliation: Department of Internal Medicine and Biochemistry, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
authors.affiliation: 1] Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA. [2] State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Schools of Life Sciences and Pharmacy, Fudan University, Shanghai, China (L.S.'s primary affiliation).
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
authors.affiliation: Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Paules
authors.affiliation: Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Auerbach
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
mesh_terms: D000818:Animals; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017423:Sequence Analysis, RNA
chemical_list: D012333:RNA, Messenger