Comprehensive benchmarking of software for mapping whole genome bisulfite data: from read alignment to DNA methylation analysis.

Autor: Nunn A; ecSeq Bioinformatics GmbH, Sternwartenstraße 29, 04103, Saxony, Germany.; Institut für Informatik, Universität Leipzig, Härtelstraße 16-18, 04107, Saxony, Germany., Otto C; ecSeq Bioinformatics GmbH, Sternwartenstraße 29, 04103, Saxony, Germany., Stadler PF; Institut für Informatik, Universität Leipzig, Härtelstraße 16-18, 04107, Saxony, Germany., Langenberger D; ecSeq Bioinformatics GmbH, Leipzig, Germany.
Jazyk: angličtina
Zdroj: Briefings in bioinformatics [Brief Bioinform] 2021 Sep 02; Vol. 22 (5).
DOI: 10.1093/bib/bbab021
Abstrakt: Whole genome bisulfite sequencing is currently at the forefront of epigenetic analysis, facilitating the nucleotide-level resolution of 5-methylcytosine (5mC) on a genome-wide scale. Specialized software have been developed to accommodate the unique difficulties in aligning such sequencing reads to a given reference, building on the knowledge acquired from model organisms such as human, or Arabidopsis thaliana. As the field of epigenetics expands its purview to non-model plant species, new challenges arise which bring into question the suitability of previously established tools. Herein, nine short-read aligners are evaluated: Bismark, BS-Seeker2, BSMAP, BWA-meth, ERNE-BS5, GEM3, GSNAP, Last and segemehl. Precision-recall of simulated alignments, in comparison to real sequencing data obtained from three natural accessions, reveals on-balance that BWA-meth and BSMAP are able to make the best use of the data during mapping. The influence of difficult-to-map regions, characterized by deviations in sequencing depth over repeat annotations, is evaluated in terms of the mean absolute deviation of the resulting methylation calls in comparison to a realistic methylome. Downstream methylation analysis is responsive to the handling of multi-mapping reads relative to mapping quality (MAPQ), and potentially susceptible to bias arising from the increased sequence complexity of densely methylated reads.
(© The Author(s) 2021. Published by Oxford University Press.)
Databáze: MEDLINE
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