Gappy TotalReCaller for RNASeq Base-Calling and Mapping

Understanding complex mammalian biology depends crucially on our ability to define a precise map of all the transcripts encoded in a genome, and to measure their relative abundances. A promising assay depends on RNASeq approaches, which builds on next generation sequencing pipelines capable of interrogating cDNAs extracted from a cell. The underlying pipeline starts with base-calling, collect the sequence reads and interpret the raw-read in terms of transcripts that are grouped with respect to different splice-variant isoforms of a messenger RNA. We address a very basic problem involved in all of these pipeline, namely accurate Bayesian base-calling, which could combine the analog intensity data with suitable underlying priors on base-composition in the transcripts. In the context of sequencing genomic DNA, a powerful approach for base-calling has been developed in the TotalReCaller pipeline. For these purposes, it uses a suitable reference whole-genome sequence in a compressed self-indexed format to derive its priors. However, TotalReCaller faces many new challenges in the transcriptomic domain, especially since we still lack a fully annotated library of all possible transcripts, and hence a sufficiently good prior. There are ...Continue Reading