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BiocMAP: A Bioconductor-friendly, GPU-Accelerated Pipeline for Bisulfite-Sequencing Data

View ORCID ProfileNicholas J Eagles, View ORCID ProfileRichard Wilton, View ORCID ProfileAndrew E. Jaffe, View ORCID ProfileLeonardo Collado-Torres
doi: https://doi.org/10.1101/2022.04.20.488947
Nicholas J Eagles
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 21205 Baltimore, USA
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Richard Wilton
2Department of Physics and Astronomy, Johns Hopkins University, 21218 Baltimore, USA
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Andrew E. Jaffe
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 21205 Baltimore, USA
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Leonardo Collado-Torres
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 21205 Baltimore, USA
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  • ORCID record for Leonardo Collado-Torres
  • For correspondence: lcolladotor@gmail.com
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Abstract

Background Bisulfite sequencing is a powerful tool for profiling genomic methylation, an epigenetic modification critical in the understanding of cancer, psychiatric disorders, and many other conditions. Raw data generated by whole genome bisulfite sequencing (WGBS) requires several computational steps before it is ready for statistical analysis, and particular care is required to process data in a timely and memory-efficient manner. Alignment to a reference genome is one of the most computationally demanding steps in a WGBS workflow, taking several hours or even days with commonly used WGBS-specific alignment software. This naturally motivates the creation of computational workflows that can utilize GPU-based alignment software to greatly speed up the bottleneck step. In addition, WGBS produces raw data that is large and often unwieldy; a lack of memory-efficient representation of data by existing pipelines renders WGBS impractical or impossible to many researchers.

Results We present BiocMAP, a Bioconductor-friendly Methylation Analysis Pipeline consisting of two modules, to address the above concerns. The first module performs computationally-intensive read alignment using Arioc, a GPU-accelerated short-read aligner. The extraction module extracts and merges DNA methylation proportions - the fractions of methylated cytosines across all cells in a sample at a given genomic site. Since GPUs are not always available on the same computing environments where traditional CPU-based analyses are convenient, BiocMAP is split into two modules, with just the alignment module requiring an available GPU. Bioconductor-based output objects in R utilize an on-disk data representation to drastically reduce required main memory and make WGBS projects computationally feasible to more researchers.

Conclusions BiocMAP is implemented using Nextflow and available at http://research.libd.org/BiocMAP/. To enable reproducible analysis across a variety of typical computing environments, BiocMAP can be containerized with Docker or Singularity, and executed locally or with the SLURM or SGE scheduling engines. By providing Bioconductor objects, BiocMAP’s output can be integrated with powerful analytical open source software for analyzing methylation data.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • http://research.libd.org/BiocMAP/

  • Abbreviations

    BiocMAP
    Bioconductor-friendly Nextflow-based Methylation Analysis Pipeline
    CpG
    Cytosine preceding a Guanine (methylation context)
    CpH
    Cytosine preceding a nucleotide other than Guanine (methylation context)
    CHG
    Cytosine followed by non-Guanine nucleotide, then Guanine (methylation context)
    CHH
    Cytosine followed by two nucleotides other than Guanine (methylation context)
    CPU
    Central Processing Unit
    CUDA
    Compute Unified Device Architecture
    DMR
    Differentially Methylated Region
    GPU
    Graphics Processing Unit
    HPC
    High Performance Computing
    NCBI
    National Center for Biotechnology Information
    RAM
    Random Access Memory
    SGE
    Sun Grid Engine or Son of Grid Engine
    SLURM
    Simple Linux Utility for Resource Management
    SRA
    Sequence Read Archive
    WGBS
    Whole Genome Bisulfite Sequencing
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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    Posted April 21, 2022.
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    BiocMAP: A Bioconductor-friendly, GPU-Accelerated Pipeline for Bisulfite-Sequencing Data
    Nicholas J Eagles, Richard Wilton, Andrew E. Jaffe, Leonardo Collado-Torres
    bioRxiv 2022.04.20.488947; doi: https://doi.org/10.1101/2022.04.20.488947
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    BiocMAP: A Bioconductor-friendly, GPU-Accelerated Pipeline for Bisulfite-Sequencing Data
    Nicholas J Eagles, Richard Wilton, Andrew E. Jaffe, Leonardo Collado-Torres
    bioRxiv 2022.04.20.488947; doi: https://doi.org/10.1101/2022.04.20.488947

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