LuxRep
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Journal Title
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Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Date
2022-12
Major/Subject
Mcode
Degree programme
Language
en
Pages
19
1-19
1-19
Series
BMC Bioinformatics, Volume 23, issue 1
Abstract
Background: DNA methylation is commonly measured using bisulfite sequencing (BS-seq). The quality of a BS-seq library is measured by its bisulfite conversion efficiency. Libraries with low conversion rates are typically excluded from analysis resulting in reduced coverage and increased costs. Results: We have developed a probabilistic method and software, LuxRep, that implements a general linear model and simultaneously accounts for technical replicates (libraries from the same biological sample) from different bisulfite-converted DNA libraries. Using simulations and actual DNA methylation data, we show that including technical replicates with low bisulfite conversion rates generates more accurate estimates of methylation levels and differentially methylated sites. Moreover, using variational inference speeds up computation time necessary for whole genome analysis. Conclusions: In this work we show that taking into account technical replicates (i.e. libraries) of BS-seq data of varying bisulfite conversion rates, with their corresponding experimental parameters, improves methylation level estimation and differential methylation detection.Description
Funding Information: We acknowledge the computational resources provided by the Aalto Science-IT project and the Finnish Functional Genomics Centre and Biocenter Finland. Funding Information: This work was supported by the Academy of Finland (292660, 311584, 335436). The funding body played no role in the design of the study, the collection, analysis, interpretation of data, or in writing the manuscript. Publisher Copyright: © 2022, The Author(s).
Keywords
Bisulfite sequencing, Methylation, Probabilistic
Other note
Citation
Malonzo , M H , Halla-aho , V , Konki , M , Lund , R J & Lähdesmäki , H 2022 , ' LuxRep : a technical replicate-aware method for bisulfite sequencing data analysis ' , BMC Bioinformatics , vol. 23 , no. 1 , 41 , pp. 1-19 . https://doi.org/10.1186/s12859-021-04546-1