TY - JOUR

T1 - HaploCart

T2 - Human mtDNA haplogroup classification using a pangenomic reference graph

AU - Rubin, Joshua Daniel

AU - Vogel, Nicola Alexandra

AU - Gopalakrishnan, Shyam

AU - Sackett, Peter Wad

AU - Renaud, Gabriel

N1 - Publisher Copyright: © 2023 Rubin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2023

Y1 - 2023

N2 - 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, a probabilistic mtDNA haplogroup classifier which uses a 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 C++ program accepts as input consensus FASTA, FASTQ, or GAM files, and outputs a text file with the haplogroup assignments of the samples along with the level of confidence in the assignments. Our work considerably reduces the amount of data required to obtain a confident mitochondrial haplogroup assignment.

AB - 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, a probabilistic mtDNA haplogroup classifier which uses a 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 C++ program accepts as input consensus FASTA, FASTQ, or GAM files, and outputs a text file with the haplogroup assignments of the samples along with the level of confidence in the assignments. Our work considerably reduces the amount of data required to obtain a confident mitochondrial haplogroup assignment.

U2 - 10.1371/journal.pcbi.1011148

DO - 10.1371/journal.pcbi.1011148

M3 - Journal article

C2 - 37285390

AN - SCOPUS:85163922433

VL - 19

JO - P L o S Computational Biology (Online)

JF - P L o S Computational Biology (Online)

SN - 1553-734X

IS - 6

M1 - e1011148

ER -