Menges, F., Narzisi, G., Mishra, B. (September 2011) TotalReCaller: improved accuracy and performance via integrated alignment and base-calling. Bioinformatics, 27 (17). pp. 2330-2337. ISSN 1367-4803
Abstract
Motivation: Currently, re-sequencing approaches use multiple modules serially to interpret raw sequencing data from next-generation sequencing platforms, while remaining oblivious to the genomic information until the final alignment step. Such approaches fail to exploit the full information from both raw sequencing data and the reference genome that can yield better quality sequence reads, SNP-calls, variant detection, as well as an alignment at the best possible location in the reference genome. Thus, there is a need for novel reference-guided bioinformatics algorithms for interpreting analog signals representing sequences of the bases ({A, C, G, T}), while simultaneously aligning possible sequence reads to a source reference genome whenever available. Results: Here, we propose a new base-calling algorithm, TotalReCaller, to achieve improved performance. A linear error model for the raw intensity data and Burrows-Wheeler transform (BWT) based alignment are combined utilizing a Bayesian score function, which is then globally optimized over all possible genomic locations using an efficient branch-and-bound approach. The algorithm has been implemented in soft- and hardware [field-programmable gate array (FPGA)] to achieve real-time performance. Empirical results on real high-throughput Illumina data were used to evaluate TotalReCaller's performance relative to its peers-Bustard, BayesCall, Ibis and Rolexa-based on several criteria, particularly those important in clinical and scientific applications. Namely, it was evaluated for (i) its base-calling speed and throughput, (ii) its read accuracy and (iii) its specificity and sensitivity in variant calling.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | short read alignment genome generation ultrafast search blast tool |
| Subjects: | bioinformatics bioinformatics > genomics and proteomics Investigative techniques and equipment Investigative techniques and equipment > assays bioinformatics > genomics and proteomics > computers > computer software Investigative techniques and equipment > whole exome sequencing Investigative techniques and equipment > assays > whole exome sequencing |
| CSHL Authors: | |
| Communities: | CSHL labs > Wigler lab |
| Depositing User: | Matt Covey |
| Date: | 1 September 2011 |
| Date Deposited: | 06 Feb 2013 17:44 |
| Last Modified: | 06 Feb 2013 17:44 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27177 |
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