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 VG's 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 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.

Haplogrep 3 - an interactive haplogroup classification and analysis platform

“…HaploTracker ( 20 ) works well for partial FASTA sequences, a feature which has also been integrated in Haplogrep 3. HaploCart1.0 ( 21 ) uses a novel and promising pangenome reference structure eliminating problems when the sample is identical to the rCRS but is currently too computational expensive to run on a large set of samples. MitoSuite ( 22 ) uses Haplogrep for mtDNA classification but also includes several tools to further investigate variants.…”

soibean: High-resolution Taxonomic Identification of Ancient Environmental DNA Using Mitochondrial Pangenome Graphs

“…In these cases, we treat 6 7 of all bases as a sequencing error with a probability of ϵ 3 and 1 7 of all bases as match with probability 1 − ϵ. ϵ is directly derived from the base quality reported from the sequencer. This is a slight update of the model for unsupported bases, which was used in HaploCart, another vgan subcommand [52], which we find to be more accurate empirically as the taxa used in the soibean database have a higher genetic divergence than human mitochondrial haplotypes.…”

Resolving the clutter of naming “Eve’s” descendants

“…A primary assignment of haplogroup names to haplotypes based on a set of mutations present in a given sequence. This step is commonly performed by haplogroup callers such as HaploGrep3 [11], HaploCart [14], and HaploGrouper [15]. 3) Algorithm-Based Groupings (ABG) -i.e.…”