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      A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages

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          Abstract

          The rat has been used extensively as a model for evaluating chemical toxicities and for understanding drug mechanisms. However, its transcriptome across multiple organs, or developmental stages, has not yet been reported. Here we show, as part of the SEQC consortium efforts, a comprehensive rat transcriptomic BodyMap created by performing RNA-Seq on 320 samples from 11 organs of both sexes of juvenile, adolescent, adult and aged Fischer 344 rats. We catalogue the expression profiles of 40,064 genes, 65,167 transcripts, 31,909 alternatively spliced transcript variants and 2,367 non-coding genes/non-coding RNAs (ncRNAs) annotated in AceView. We find that organ-enriched, differentially expressed genes reflect the known organ-specific biological activities. A large number of transcripts show organ-specific, age-dependent or sex-specific differential expression patterns. We create a web-based, open-access rat BodyMap database of expression profiles with crosslinks to other widely used databases, anticipating that it will serve as a primary resource for biomedical research using the rat model.

          Abstract

          Gene expression is highly variable between tissues, and changes during development and with age. Here, the authors provide a comprehensive RNA-Seq analysis of the rat transcriptome, spanning eleven organs, four developmental stages and both sexes.

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          Most cited references24

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          FlyAtlas, a new online resource, provides the most comprehensive view yet of expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the data shows that a significant fraction of the genome is expressed with great tissue specificity in the adult, demonstrating the need for the functional genomic community to embrace a wide range of functional phenotypes. Well-known developmental genes are often reused in surprising tissues in the adult, suggesting new functions. The homologs of many human genetic disease loci show selective expression in the Drosophila tissues analogous to the affected human tissues, providing a useful filter for potential candidate genes. Additionally, the contributions of each tissue to the whole-fly array signal can be calculated, demonstrating the limitations of whole-organism approaches to functional genomics and allowing modeling of a simple tissue fractionation procedure that should improve detection of weak or tissue-specific signals.
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            Identification of functional elements and regulatory circuits by Drosophila modENCODE.

            To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                10 February 2014
                : 5
                : 3230
                Affiliations
                [1 ]Center for Pharmacogenomics, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Schools of Life Sciences and Pharmacy, Fudan University , Shanghai 201203, China
                [2 ]National Center for Toxicological Research, Food and Drug Administration , Jefferson, Arkansas 92079, USA
                [3 ]Functional Genomics Core, Beckman Research Institute, City of Hope , Duarte, California 91010, USA
                [4 ]Army Institute of Public Health, U.S. Army Public Health Command, Aberdeen Proving Ground , Maryland 21010, USA
                [5 ]Computation Biology and Bioinformatics, IP & Science, Thomson Reuters , London EC1N 8JS, UK
                [6 ]SAS Institute Inc. , Cary, North Carolina 27513, USA
                [7 ]Expression Analysis Inc. , Durham, North Carolina 27713, USA
                [8 ]The Center for Bioinformatics and The Institute of Biomedical Sciences, College of Life Science , Shanghai 200241, China
                [9 ]Johns Hopkins University School of Medicine , Baltimore, Maryland 21205, USA
                [10 ]Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences , Winston-Salem, North Carolina 27157, USA
                [11 ]Department of Basic Sciences, School of Medicine, Loma Linda University , Loma Linda, California 92350, USA
                [12 ]Department of Physiology & Biophysics and the Institute for Computational Biomedicine, Cornell University , New York, New York 10021, USA
                [13 ]National Center for Biotechnology Information, National Institutes of Health , Bethesda, Maryland 20894, USA
                [14 ]Fudan-Zhangjiang Center for Clinical Genomics and Zhangjiang Center for Translational Medicine , Shanghai 201203, China
                [15 ]Center for Genomics and Division of Microbiology & Molecular Genetics, School of Medicine, Loma Linda University , Loma Linda, California 92350, USA
                [16 ]These authors contributed equally to this work
                Author notes
                Article
                ncomms4230
                10.1038/ncomms4230
                3926002
                24510058
                8be8c829-3a21-4e6c-af87-30eadca3ded1
                Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 07 June 2013
                : 10 January 2014
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