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Taudt, A.* ; Roquis, D.* ; Vidalis, A.* ; Wardenaar, R.* ; Johannes, F.* ; Colomé-Tatché, M.

METHimpute: Imputation-guided construction of complete methylomes from WGBS data.

BMC Genomics 19:444 (2018)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background: Whole-genome bisulfite sequencing (WGBS) has become the standard method for interrogating plant methylomes at base resolution. However, deep WGBS measurements remain cost prohibitive for large, complex genomes and for population-level studies. As a result, most published plant methylomes are sequenced far below saturation, with a large proportion of cytosines having either missing data or insufficient coverage. Results: Here we present METHimpute, a Hidden Markov Model (HMM) based imputation algorithm for the analysis of WGBS data. Unlike existing methods, METHimpute enables the construction of complete methylomes by inferring the methylation status and level of all cytosines in the genome regardless of coverage. Application of METHimpute to maize, rice and Arabidopsis shows that the algorithm infers cytosine-resolution methylomes with high accuracy from data as low as 6X, compared to data with 60X, thus making it a cost-effective solution for large-scale studies. Conclusions: METHimpute provides methylation status calls and levels for all cytosines in the genome regardless of coverage, thus yielding complete methylomes even with low-coverage WGBS datasets. The method has been extensively tested in plants, but should also be applicable to other species. An implementation is available on Bioconductor.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Hidden Markov Model ; Imputation ; Methylation ; Whole-genome Bisulfite Sequencing; Cell-line Thp-1; In-vitro; Hacat Keratinocytes; Alkaloid Berberine; Dendritic Cells; Injury; Skin; Sensitization; Expression; Toxicity
ISSN (print) / ISBN 1471-2164
e-ISSN 1471-2164
Journal BMC Genomics
Quellenangaben Volume: 19, Issue: 1, Pages: , Article Number: 444 Supplement: ,
Publisher BioMed Central
Publishing Place Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)