Sunday, May 9, 2010

BS Seeker: precise mapping for bisulfite sequencing

BS Seeker: precise mapping for bisulfite sequencing

Pubmed Direct Link

Yet another alignment algorithm (YAAA), this time for bisulfite sequencing. This algorithm, developed in the same lab as the BS-SEQ (Jacobsen at UCLA) and called BS-SEEKER, purports to be more versatile and faster. I am of the philosophy that an aligner should be "as fast as it needs to be" to achieve the desired level of sensitivity, so the latter claim is not as interesting as the former claim. Basically, it needs to find what you are looking for first, then lets worry about speed. The abstract claims sensitivity and accuracy, so lets see if it delivers.

Surprisingly, the authors do not implement their own algorithm, but instead use bowtie. I do not recommend bowtie since it does not handle insertions or deletions, which can significantly impact mapping accuracy (see this partial discussion). Nevertheless, bowtie should be able to be replaced by other algorithms, since the novel contribution of BS-SEEKER is the separation of the four types of BS reads.

The evaluations were very lite on information, mapping reads to only human chromosome 21, and not accounting for higher sequencing error rates or indels. Furthermore, BS-SEEKER is not the best algorithm in every situation according to their own results, in some cases MAQ or RMAP performing better in terms of accuracy/sensitivity/timing.  Their novel contribution is the application of bowtie, but beyond that I am not seeing the value of this method, with the exception if you use the Cokus et al. library construction. More evaluation of this method is necessary to convince others to use it.

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