RT Journal A1 Kao, Wei-Chun A1 Stevens, Kristian A1 Song, Yun S. T1 BayesCall: A model-based base-calling algorithm for high-throughput short-read sequencing JF Genome Research JO Genome Research YR 2009 FD October 01 VO 19 IS 10 SP 1884 OP 1895 DO 10.1101/gr.095299.109 UL http://genome.cshlp.org/content/19/10/1884.abstract AB Extracting sequence information from raw images of fluorescence is the foundation underlying several high-throughput sequencing platforms. Some of the main challenges associated with this technology include reducing the error rate, assigning accurate base-specific quality scores, and reducing the cost of sequencing by increasing the throughput per run. To demonstrate how computational advancement can help to meet these challenges, a novel model-based base-calling algorithm, BayesCall, is introduced for the Illumina sequencing platform. Being founded on the tools of statistical learning, BayesCall is flexible enough to incorporate various features of the sequencing process. In particular, it can easily incorporate time-dependent parameters and model residual effects. This new approach significantly improves the accuracy over Illumina's base-caller Bustard, particularly in the later cycles of a sequencing run. For 76-cycle data on a standard viral sample, phiX174, BayesCall improves Bustard's average per-base error rate by ∼51%. The probability of observing each base can be readily computed in BayesCall, and this probability can be transformed into a useful base-specific quality score with a high discrimination ability. A detailed study of BayesCall's performance is presented here.