PD_NGSAtlas: a reference database combining next-generation sequencing epigenomic and transcriptomic data for psychiatric disorders

BackgroundPsychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) are projected to lead the global disease burden within the next decade. Several lines of evidence suggest that epigenetic- or genetic-mediated dysfunction is frequently present in these disorders. To date, the inheritance patterns have been complicated by the problem of integrating epigenomic and transcriptomic factors that have yet to be elucidated. Therefore, there is a need to build a comprehensive database for storing epigenomic and transcriptomic data relating to psychiatric disorders.DescriptionWe have developed the PD_NGSAtlas, which focuses on the efficient storage of epigenomic and transcriptomic data based on next-generation sequencing and on the quantitative analyses of epigenetic and transcriptional alterations involved in psychiatric disorders. The current release of the PD_NGSAtlas contains 43 DNA methylation profiles and 37 transcription profiles detected by MeDIP-Seq and RNA-Seq, respectively, in two distinct brain regions and peripheral blood of SZ, BP and non-psychiatric controls. In addition to these data that were generated in-house, we have included, and will continue to include, published DNA methylation and gene expression data from other research groups, with a focus on psychiatric disorders. A flexible query engine has been developed for the acquisition of methylation profiles and transcription profiles for special genes or genomic regions of interest of the selected samples. Furthermore, the PD_NGSAtlas offers online tools for identifying aberrantly methylated and expressed events involved in psychiatric disorders. A genome browser has been developed to provide integrative and detailed views of multidimensional data in a given genomic context, which can help researchers understand molecular mechanisms from epigenetic and transcriptional perspectives. Moreover, users can download the methylation and transcription data for further analyses.ConclusionsThe PD_NGSAtlas aims to provide storage of epigenomic and transcriptomic data as well as quantitative analyses of epigenetic and transcriptional alterations involved in psychiatric disorders. The PD_NGSAtlas will be a valuable data resource and will enable researchers to investigate the pathophysiology and aetiology of disease in detail. The database is available at http://bioinfo.hrbmu.edu.cn/pd_ngsatlas/.

[1]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[2]  Yun Xiao,et al.  The DNA Methylome and Transcriptome of Different Brain Regions in Schizophrenia and Bipolar Disorder , 2014, PloS one.

[3]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[4]  Patrick F. Sullivan,et al.  Genetic architectures of psychiatric disorders: the emerging picture and its implications , 2012, Nature Reviews Genetics.

[5]  A. Bird,et al.  DNA methylation landscapes: provocative insights from epigenomics , 2008, Nature Reviews Genetics.

[6]  Jie Lv,et al.  DiseaseMeth: a human disease methylation database , 2011, Nucleic Acids Res..

[7]  N. Craddock,et al.  The genetics of schizophrenia and bipolar disorder: dissecting psychosis , 2005, Journal of Medical Genetics.

[8]  Mark D. Robinson,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[9]  Marquis P. Vawter,et al.  Analysis of whole genome biomarker expression in blood and brain , 2010, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[10]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.

[11]  Siu-Ming Yiu,et al.  SOAP2: an improved ultrafast tool for short read alignment , 2009, Bioinform..

[12]  Sun-Chong Wang,et al.  Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. , 2008, American journal of human genetics.

[13]  R. Dobson,et al.  Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood , 2012, Genome Biology.

[14]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[15]  B. Crespo-Facorro,et al.  Inflammatory and immune response genes have significantly altered expression in schizophrenia , 2013, Molecular Psychiatry.

[16]  Xuegong Zhang,et al.  DEGseq: an R package for identifying differentially expressed genes from RNA-seq data , 2010, Bioinform..

[17]  A. Bird DNA methylation patterns and epigenetic memory. , 2002, Genes & development.

[18]  Michael Hackenberg,et al.  NGSmethDB: a database for next-generation sequencing single-cytosine-resolution DNA methylation data , 2010, Nucleic Acids Res..

[19]  Amy M. Jimenez,et al.  Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia , 2008, Development and Psychopathology.

[20]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[21]  Yurong Xin,et al.  MethylomeDB: a database of DNA methylation profiles of the brain , 2011, Nucleic Acids Res..

[22]  C. Connor,et al.  DNA methylation changes in schizophrenia and bipolar disorder , 2008, Epigenetics.

[23]  ENCODEConsortium,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[24]  Robin M. Murray,et al.  Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population , 2012, PLoS genetics.

[25]  L. Stein,et al.  JBrowse: a next-generation genome browser. , 2009, Genome research.

[26]  Vladimir I. Vladimirov,et al.  ZNF804A and cortical structure in schizophrenia: in vivo and postmortem studies. , 2014, Schizophrenia bulletin.

[27]  Jing Zhang,et al.  MethBank: a database integrating next-generation sequencing single-base-resolution DNA methylation programming data , 2014, Nucleic Acids Res..

[28]  Mark S. Doderer,et al.  CMS: A Web-Based System for Visualization and Analysis of Genome-Wide Methylation Data of Human Cancers , 2013, PloS one.

[29]  Eric C. Griffith,et al.  Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2 , 2003, Science.

[30]  B. Williams,et al.  Mapping and quantifying mammalian transcriptomes by RNA-Seq , 2008, Nature Methods.

[31]  J. Mill,et al.  Epigenetic Studies of Psychosis: Current Findings, Methodological Approaches, and Implications for Postmortem Research , 2011, Biological Psychiatry.

[32]  L. Wilkinson,et al.  Genomic imprinting and the social brain , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[33]  A. Hayashi‐Takagi,et al.  Peripheral Biomarkers Revisited: Integrative Profiling of Peripheral Samples for Psychiatric Research , 2014, Biological Psychiatry.

[34]  P. Goldman-Rakic,et al.  Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. Variability in locations of areas 9 and 46 and relationship to the Talairach Coordinate System. , 1995, Cerebral cortex.

[35]  J. Sweatt,et al.  Epigenetic Regulation of bdnf Gene Transcription in the Consolidation of Fear Memory , 2008, The Journal of Neuroscience.

[36]  Daisuke Hattori,et al.  DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation , 2003, Science.

[37]  Fei Gao,et al.  Hypermethylation in the ZBTB20 gene is associated with major depressive disorder , 2014, Genome Biology.

[38]  Paul J. Harrison Schizophrenia: a disorder of neurodevelopment? , 1997, Current Opinion in Neurobiology.

[39]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[40]  H. Nicolini,et al.  Genome-Wide Methylome Analyses Reveal Novel Epigenetic Regulation Patterns in Schizophrenia and Bipolar Disorder , 2015, BioMed research international.

[41]  Charles M Perou,et al.  Evaluating the comparability of gene expression in blood and brain , 2006, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[42]  Vikram Patel,et al.  Global mental health: a new global health field comes of age. , 2010, JAMA.

[43]  A. Guidotti,et al.  Reelin promoter hypermethylation in schizophrenia. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Madeleine P. Ball,et al.  Neuronal activity modifies DNA methylation landscape in the adult brain , 2011, Nature Neuroscience.

[45]  J. Mill,et al.  Brain weight in males is correlated with DNA methylation at IGF2 , 2010, Molecular Psychiatry.

[46]  Kazuo Yamada,et al.  DNA Methylation Status of SOX10 Correlates with Its Downregulation and Oligodendrocyte Dysfunction in Schizophrenia , 2005, The Journal of Neuroscience.

[47]  M. McInnis,et al.  Psychiatric genetics: progress amid controversy , 2008, Nature Reviews Genetics.

[48]  Michio Suzuki,et al.  Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population , 2010, Journal of Human Genetics.

[49]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .