HaploGrep 2: mitochondrial haplogroup classification in the era of high-throughput sequencing

Abstract

Mitochondrial DNA (mtDNA) profiles can be classified into phylogenetic clusters (haplogroups), which is of great relevance for evolutionary, forensic and medical genetics. With the extensive growth of the underlying phylogenetic tree summarizing the published mtDNA sequences, the manual process of haplogroup classification would be too time-consuming. The previously published classification tool HaploGrep provided an automatic way to address this issue. Here, we present the completely updated version HaploGrep 2 offering several advanced features, including a generic rule-based system for immediate quality control (QC). This allows detecting artificial recombinants and missing variants as well as annotating rare and phantom mutations. Furthermore, the handling of high-throughput data in form of VCF files is now directly supported. For data output, several graphical reports are generated in real time, such as a multiple sequence alignment format, a VCF format and extended haplogroup QC reports, all viewable directly within the application. In addition, HaploGrep 2 generates a publication-ready phylogenetic tree of all input samples encoded relative to the revised Cambridge Reference Sequence. Finally, new distance measures and optimizations of the algorithm increase accuracy and speed-up the application. HaploGrep 2 can be accessed freely and without any registration at http://haplogrep.uibk.ac.at.