Universität zu Köln

Lienhard, Matthias, Grasse, Sabrina, Rolff, Jana, Frese, Steffen, Schirmer, Uwe, Becker, Michael, Boerno, Stefan, Timmermann, Bernd, Chavez, Lukas ORCID: 0000-0002-8718-8848, Sueltmann, Holger, Leschber, Gunda, Fichtner, Iduna, Schweiger, Michal R. and Herwig, Ralf ORCID: 0000-0002-9335-1760 (2017). QSEA-modelling of genome-wide DNA methylation from sequencing enrichment experiments. Nucleic Acids Res., 45 (6). OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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Abstract

Genome-wide enrichment of methylated DNA followed by sequencing (MeDIP-seq) offers a reasonable compromise between experimental costs and genomic coverage. However, the computational analysis of these experiments is complex, and quantification of the enrichment signals in terms of absolute levels of methylation requires specific transformation. In this work, we present QSEA, Quantitative Sequence Enrichment Analysis, a comprehensive workflow for the modelling and subsequent quantification of MeDIP-seq data. As the central part of the workflow we have developed a Bayesian statistical model that transforms the enrichment read counts to absolute levels of methylation and, thus, enhances interpretability and facilitates comparison with other methylation assays. We suggest several calibration strategies for the critical parameters of the model, either using additional data or fairly general assumptions. By comparing the results with bisulfite sequencing (BS) validation data, we show the improvement of QSEA over existing methods. Additionally, we generated a clinically relevant benchmark data set consisting of methylation enrichment experiments (MeDIP-seq), BS-based validation experiments (Methyl-seq) aswell as gene expression experiments (RNA-seq) derived from non-small cell lung cancer patients, and show that the workflow retrieves well-known lung tumour methylation markers that are causative for gene expression changes, demonstrating the applicability of QSEA for clinical studies. QSEA is implemented in R and available from the Bioconductor repository 3.4 (www.bioconductor.org/packages/qsea).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lienhard, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Grasse, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rolff, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Frese, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Schirmer, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Boerno, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmermann, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Chavez, Lukas UNSPECIFIED orcid.org/0000-0002-8718-8848 UNSPECIFIED Sueltmann, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Leschber, Gunda UNSPECIFIED UNSPECIFIED UNSPECIFIED Fichtner, Iduna UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweiger, Michal R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herwig, Ralf UNSPECIFIED orcid.org/0000-0002-9335-1760 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-234097
DOI:	10.1093/nar/gkw1193
Journal or Publication Title:	Nucleic Acids Res.
Volume:	45
Number:	6
Date:	2017
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1362-4962
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIGH-THROUGHPUT; READ ALIGNMENT; CANCER; RESOLUTION; DIFFERENTIATION; DIAGNOSIS; BIOMARKER; CAPTURE; SITES; CELLS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23409