An alignment algorithm for bisulfite sequencing using the Applied Biosystems SOLiD System.
CONCLUSIONS
Bisulfite sequencing allows cytosine methylation, an important epigenetic marker, to be detected via nucleotide substitutions. Since the Applied Biosystems SOLiD System uses a unique di-base encoding that increases confidence in the detection of nucleotide substitutions, it is a potentially advantageous platform for this application. However, the di-base encoding also makes reads with many nucleotide substitutions difficult to align to a reference sequence with existing tools, preventing the platform's potential utility for bisulfite sequencing from being realized. Here, we present SOCS-B, a reference-based, un-gapped alignment algorithm for the SOLiD System that is tolerant of both bisulfite-induced nucleotide substitutions and a parametric number of sequencing errors, facilitating bisulfite sequencing on this platform. An implementation of the algorithm has been integrated with the previously reported SOCS alignment tool, and was used to align CpG methylation-enriched Arabidopsis thaliana bisulfite sequence data, exhibiting a 2-fold increase in sensitivity compared to existing methods for aligning SOLiD bisulfite data.


BACKGROUND
Executables, source code, and sample data are available at http://solidsoftwaretools.com/gf/project/socs/
Ondov
Brian D
BD
National Biodefense Analysis and Countermeasures Center, 110 Thomas Johnson Drive, Frederick, MD 21702, USA.
Cochran
Charles
C
Landers
Mark
M
Meredith
Gavin D
GD
Dudas
Miroslav
M
Bergman
Nicholas H
NH
D000465:Algorithms; D017360:Arabidopsis / Q000235:genetics; D016415:Sequence Alignment / Q000295:instrumentation / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods*; D013447:Sulfites
D013447:Sulfites; C042345:hydrogen sulfite