HaploCart: Human mtDNA Haplogroup Classification Using a Pangenomic Reference Graph

Abstract

Current mitochondrial DNA (mtDNA) haplogroup classification tools map reads to a single reference genome and perform inference based on the detected mutations to this reference. This approach biases haplogroup assignments towards the reference and prohibits accurate calculations of the uncertainty in assignment. We present HaploCart, an mtDNA haplogroup classifier which uses VGs pangenomic reference graph framework together with principles of Bayesian inference. We demonstrate that our approach significantly outperforms available tools by being more robust to lower coverage or incomplete consensus sequences and producing phylogenetically-aware confidence scores that are unbiased towards any haplogroup. HaploCart is available both as a command-line tool and through a user-friendly web interface. The program written in C++ accepts as input consensus FASTA, FASTQ, or GAM files, and outputs a text file with the haplogroup assignments along with confidence estimates. Our work considerably reduces the amount of data required to obtain a confident mitochondrial haplogroup assignment. HaploCart is available as a command-line tool at https://github.com/grenaud/vgan and as a web server at https://services.healthtech.dtu.dk/service. php?HaploCart.