Thursday, February 14, 2013

Fwd: An automated ensemble method for combining and evaluating genomic variants from multiple callers « Blue Collar Bioinformatics

A very nice comparison analysis and integration "cloud-tool" for variant calling

Fwd: please follow footer link

A key goal of the Archon Genomics X Prize infrastructure is development of a set of highly accurate reference genome variants. I’ve described our work preparing these reference genomes, and specifically defined the challenges behind merging genomic variant calls from multiple technologies and calling methods. Comparing calls from two different calling methods, for example GATK and samtools mpileup, produces a large number of differing variants which need reconciliation. Taking the overlapping subset from multiple callers is too conservative and will miss real variations, while including all calls is too liberal and introduces false positives.

Here I’ll describe a fully automated approach for preparing an accurate set of combined variant calls. Ensemble machine learning methods are a powerful way to incorporate inputs from multiple models. We use a heuristic and support vector machine (SVM) algorithm to consolidate variants, producing a final set of calls with better sensitivity and specificity than current best practice methods. The approach is open source, fully automated and generalizable to both human diploid sequencing as well as X Prize haploid reference fosmids.

We use a pair of replicates from EdgeBio’s clinical exome sequencing pipeline to prepare ensemble variant calls in the widely studied HapMap NA12878 genome. Compared to variants from a single calling method, the ensemble method produced more concordant variants when comparing the replicates, with fewer discordants. The finalized ensemble calls also provide a useful method to compare strengths and weaknesses of individual calling methods. The implementation is freely available and I’ll discuss how to get it running on your data so you can use, critique and extend the methods. This work is a collaboration between Harvard School of Public Health, EdgeBio and NIST.

(Via Blue Collar Bioinformatics.)