Evidence map›Paper›PMID 27913729›Full record

ArticleNucleic acids research2017

QSEA-modelling of genome-wide DNA methylation from sequencing enrichment experiments.

Matthias Lienhard, Sabrina Grasse, Jana Rolff, Steffen Frese, Uwe Schirmer, Michael Becker, Stefan Börno, Bernd Timmermann, Lukas Chavez, Holger Sültmann and 4 more

Abstract readEvaluation Study
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Matthias LienhardDepartment of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin 14195, Germany.
Sabrina GrasseFunctional Epigenomics, University Hospital Cologne, Cologne 50937, Germany.
Jana RolffExperimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin 13125, Germany.
Steffen FreseDepartment of Thoracic Surgery, ELK Berlin Chest Hospital, Berlin 13125, Germany.
Uwe SchirmerCancer Genome Research Group, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany.
Michael BeckerExperimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin 13125, Germany.
Stefan BörnoSequencing Core Facility, Max-Planck-Institute for Molecular Genetics, Berlin 14195, Germany.
Bernd TimmermannSequencing Core Facility, Max-Planck-Institute for Molecular Genetics, Berlin 14195, Germany.
Lukas ChavezDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Holger SültmannCancer Genome Research Group, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany.
Gunda LeschberDepartment of Thoracic Surgery, ELK Berlin Chest Hospital, Berlin 13125, Germany.
Iduna FichtnerExperimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin 13125, Germany.
Michal R SchweigerFunctional Epigenomics, University Hospital Cologne, Cologne 50937, Germany.
Ralf HerwigDepartment of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin 14195, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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) as well 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).

Indexed as

DNA MethylationAnimalsBayes TheoremGene Expression RegulationGenomicsHumansLung NeoplasmsMicePromoter Regions, GeneticSequence Analysis, DNASulfitesWorkflowhydrogen sulfiteSulfites

Identifiers

PMID27913729
PMCPMC5389680

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.