Somatic calling / Improved support for targetted sequencing / VCF comparison improvements

August 25, 2016

Real Time Genomics are pleased to announce the availability of version 3.7 of our full analysis suite, RTG Core, and our utility package, RTG Tools.  This release includes new features and performance improvements. Some of the highlights of this release:

• Improvements to mapping speed when aligning targeted sequencing data. This feature makes use of a per-reference hash blacklist which is constructed once per reference genome and can yield significant speed improvement.  In addition, several changes were made to reduce peak memory use during mapping.

• Variant callers now allow the optional inclusion of expected germline allele balance terms in the Bayesian model.  In a genome-wide scale, this generally results in a reduction in false-positive calls, although sensitivity may be reduced for variants which do not follow allele balance expectations, such as mosaic de novo variants.

• Several improvements to the somatic caller. These include the ability to enable output of germline variants (due to the joint calling, accuracy of calling germline variants during somatic calling is typically higher than separately calling germline variants from the normal sample alone). The somatic caller now has the ability to explicitly model the expected somatic allelic fraction, for use in cases where the tumor heterogeneity is expected to be low. Additional options allow the output of records at sites exceeding user-specified thresholds for non-reference evidence. We have also included an AVR model specifically built for somatic calling which provides more accurate scoring than the regular germline AVR models.

• Several improvements to the variant comparison tools.  vcfeval now includes the ability to evaluate matches across confident-region boundaries according to GA4GH recommended practise.  vcfeval can be used to compare against "sample-free" VCFs such as ExAC/COSMIC/dbSNP, and the runtime has also been significantly improved.  In addition, the rocplot command can now produce precision-sensitivity graphs, and can output SVG as a more publication-ready format.

If you haven't used RTG Core before (or maybe even if you have), we suggest you run the demo-family.sh script that runs through a short end-to-end demonstration of sex-aware and pedigree-aware family variant calling, including de novo variant detection and variant evaluation with vcfeval. (It also makes a nice demo of our comprehensive simulation tools.)

For more information including downloads, see the product page for RTG Core or RTG Tools.