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BSMAP: whole genome bisulfite sequence MAPping program.

Xi Y, Li W - BMC Bioinformatics (2009)

Bottom Line: However, mapping high-throughput bisulfite reads to the reference genome remains a great challenge due to the increased searching space, reduced complexity of bisulfite sequence, asymmetric cytosine to thymine alignments, and multiple CpG heterogeneous methylation.BSMAP is the first general-purpose bisulfite mapping software.It is able to map high-throughput bisulfite reads at whole genome level with feasible memory and CPU usage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Biostatistics, Dan L Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. yxi@bcm.edu

ABSTRACT

Background: Bisulfite sequencing is a powerful technique to study DNA cytosine methylation. Bisulfite treatment followed by PCR amplification specifically converts unmethylated cytosines to thymine. Coupled with next generation sequencing technology, it is able to detect the methylation status of every cytosine in the genome. However, mapping high-throughput bisulfite reads to the reference genome remains a great challenge due to the increased searching space, reduced complexity of bisulfite sequence, asymmetric cytosine to thymine alignments, and multiple CpG heterogeneous methylation.

Results: We developed an efficient bisulfite reads mapping algorithm BSMAP to address the above issues. BSMAP combines genome hashing and bitwise masking to achieve fast and accurate bisulfite mapping. Compared with existing bisulfite mapping approaches, BSMAP is faster, more sensitive and more flexible.

Conclusion: BSMAP is the first general-purpose bisulfite mapping software. It is able to map high-throughput bisulfite reads at whole genome level with feasible memory and CPU usage. It is freely available under GPL v3 license at http://code.google.com/p/bsmap/.

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Mapping of bisulfite reads. 1) Increased search space due to the cytosine-thymine conversion in the bisulfite treatment. 2) Mapping asymmetry: thymines in bisulfite reads can be aligned with cytosines in the reference (illustrated in blue) but not the reverse.
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Figure 2: Mapping of bisulfite reads. 1) Increased search space due to the cytosine-thymine conversion in the bisulfite treatment. 2) Mapping asymmetry: thymines in bisulfite reads can be aligned with cytosines in the reference (illustrated in blue) but not the reverse.

Mentions: Third, C to T mapping is asymmetric. The T in the bisulfite reads could be mapped to either C or T in the reference but not vice versa. This phenomenon not only increases the search space for mapping but also complicates the matching process (Figure 2). Efficient implementation of such asymmetric C/T matching is critical for mapping high-throughput bisulfite reads to the reference genome and is still lacking in current short read alignment software.


BSMAP: whole genome bisulfite sequence MAPping program.

Xi Y, Li W - BMC Bioinformatics (2009)

Mapping of bisulfite reads. 1) Increased search space due to the cytosine-thymine conversion in the bisulfite treatment. 2) Mapping asymmetry: thymines in bisulfite reads can be aligned with cytosines in the reference (illustrated in blue) but not the reverse.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724425&req=5

Figure 2: Mapping of bisulfite reads. 1) Increased search space due to the cytosine-thymine conversion in the bisulfite treatment. 2) Mapping asymmetry: thymines in bisulfite reads can be aligned with cytosines in the reference (illustrated in blue) but not the reverse.
Mentions: Third, C to T mapping is asymmetric. The T in the bisulfite reads could be mapped to either C or T in the reference but not vice versa. This phenomenon not only increases the search space for mapping but also complicates the matching process (Figure 2). Efficient implementation of such asymmetric C/T matching is critical for mapping high-throughput bisulfite reads to the reference genome and is still lacking in current short read alignment software.

Bottom Line: However, mapping high-throughput bisulfite reads to the reference genome remains a great challenge due to the increased searching space, reduced complexity of bisulfite sequence, asymmetric cytosine to thymine alignments, and multiple CpG heterogeneous methylation.BSMAP is the first general-purpose bisulfite mapping software.It is able to map high-throughput bisulfite reads at whole genome level with feasible memory and CPU usage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Biostatistics, Dan L Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. yxi@bcm.edu

ABSTRACT

Background: Bisulfite sequencing is a powerful technique to study DNA cytosine methylation. Bisulfite treatment followed by PCR amplification specifically converts unmethylated cytosines to thymine. Coupled with next generation sequencing technology, it is able to detect the methylation status of every cytosine in the genome. However, mapping high-throughput bisulfite reads to the reference genome remains a great challenge due to the increased searching space, reduced complexity of bisulfite sequence, asymmetric cytosine to thymine alignments, and multiple CpG heterogeneous methylation.

Results: We developed an efficient bisulfite reads mapping algorithm BSMAP to address the above issues. BSMAP combines genome hashing and bitwise masking to achieve fast and accurate bisulfite mapping. Compared with existing bisulfite mapping approaches, BSMAP is faster, more sensitive and more flexible.

Conclusion: BSMAP is the first general-purpose bisulfite mapping software. It is able to map high-throughput bisulfite reads at whole genome level with feasible memory and CPU usage. It is freely available under GPL v3 license at http://code.google.com/p/bsmap/.

Show MeSH