{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T21:52:52Z","timestamp":1774475572744,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Horizon 2020 program","award":["764965"],"award-info":[{"award-number":["764965"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1093\/bib\/bbab021","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T15:16:12Z","timestamp":1610723772000},"source":"Crossref","is-referenced-by-count":17,"title":["Comprehensive benchmarking of software for mapping whole genome bisulfite data: from read alignment to DNA methylation analysis"],"prefix":"10.1093","volume":"22","author":[{"given":"Adam","family":"Nunn","sequence":"first","affiliation":[{"name":"ecSeq Bioinformatics GmbH, Sternwartenstra\u00dfe 29, 04103, Saxony, Germany"},{"name":"Institut f\u00fcr Informatik, Universit\u00e4t Leipzig, H\u00e4rtelstra\u00dfe 16-18, 04107, Saxony, Germany"}]},{"given":"Christian","family":"Otto","sequence":"additional","affiliation":[{"name":"ecSeq Bioinformatics GmbH, Sternwartenstra\u00dfe 29, 04103, Saxony, Germany"}]},{"given":"Peter F","family":"Stadler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Informatik, Universit\u00e4t Leipzig, H\u00e4rtelstra\u00dfe 16-18, 04107, Saxony, Germany"}]},{"given":"David","family":"Langenberger","sequence":"additional","affiliation":[{"name":"ecSeq Bioinformatics GmbH, Leipzig, Germany"}]}],"member":"286","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"issue":"5","key":"2021090815124711900_ref1","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1073\/pnas.89.5.1827","article-title":"A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual dna strands","volume":"89","author":"Frommer","year":"1992","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"2021090815124711900_ref2","first-page":"1","article-title":"Dnamod: the dna modification 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