Hans-Ulrich Klein1, Martin Schäfer1, Bo T Porse2, Marie S Hasemann2, Katja Ickstadt1, Martin Dugas1. 1. Institute of Medical Informatics, University of Münster, D-48149 Münster, Mathematical Institute, Heinrich Heine University, D-40225 Düsseldorf, Germany, The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Center (BRIC), Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark and Faculty of Statistics, TU Dortmund University, D-44221 Dortmund, Germany. 2. Institute of Medical Informatics, University of Münster, D-48149 Münster, Mathematical Institute, Heinrich Heine University, D-40225 Düsseldorf, Germany, The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Center (BRIC), Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark and Faculty of Statistics, TU Dortmund University, D-44221 Dortmund, Germany Institute of Medical Informatics, University of Münster, D-48149 Münster, Mathematical Institute, Heinrich Heine University, D-40225 Düsseldorf, Germany, The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Center (BRIC), Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark and Faculty of Statistics, TU Dortmund University, D-44221 Dortmund, Germany Institute of Medical Informatics, University of Münster, D-48149 Münster, Mathematical Institute, Heinrich Heine University, D-40225 Düsseldorf, Germany, The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Center (BRIC), Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark and Faculty of Statistics, TU Dortmund University, D-44221 Dortmund, Germany.
Abstract
MOTIVATION: Histone modifications are a key epigenetic mechanism to activate or repress the transcription of genes. Datasets of matched transcription data and histone modification data obtained by ChIP-seq exist, but methods for integrative analysis of both data types are still rare. Here, we present a novel bioinformatics approach to detect genes that show different transcript abundances between two conditions putatively caused by alterations in histone modification. RESULTS: We introduce a correlation measure for integrative analysis of ChIP-seq and gene transcription data measured by RNA sequencing or microarrays and demonstrate that a proper normalization of ChIP-seq data is crucial. We suggest applying Bayesian mixture models of different types of distributions to further study the distribution of the correlation measure. The implicit classification of the mixture models is used to detect genes with differences between two conditions in both gene transcription and histone modification. The method is applied to different datasets, and its superiority to a naive separate analysis of both data types is demonstrated. AVAILABILITY AND IMPLEMENTATION: R/Bioconductor package epigenomix. CONTACT: h.klein@uni-muenster.de Supplementary information: Supplementary data are available at Bioinformatics online.
MOTIVATION: Histone modifications are a key epigenetic mechanism to activate or repress the transcription of genes. Datasets of matched transcription data and histone modification data obtained by ChIP-seq exist, but methods for integrative analysis of both data types are still rare. Here, we present a novel bioinformatics approach to detect genes that show different transcript abundances between two conditions putatively caused by alterations in histone modification. RESULTS: We introduce a correlation measure for integrative analysis of ChIP-seq and gene transcription data measured by RNA sequencing or microarrays and demonstrate that a proper normalization of ChIP-seq data is crucial. We suggest applying Bayesian mixture models of different types of distributions to further study the distribution of the correlation measure. The implicit classification of the mixture models is used to detect genes with differences between two conditions in both gene transcription and histone modification. The method is applied to different datasets, and its superiority to a naive separate analysis of both data types is demonstrated. AVAILABILITY AND IMPLEMENTATION: R/Bioconductor package epigenomix. CONTACT: h.klein@uni-muenster.de Supplementary information: Supplementary data are available at Bioinformatics online.
Authors: Hans-Ulrich Klein; Martin Schäfer; David A Bennett; Holger Schwender; Philip L De Jager Journal: PLoS Comput Biol Date: 2020-04-07 Impact factor: 4.475
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