yHaplo: Identifying Y-Chromosome Haplogroups

David Poznik
23andMe
October, 2016

Overview

yHaplo identifies the Y-chromosome haplogroup of each male in a sample of one to millions. It does not rely on any particular genotyping modality or platform, and it is robust to missing data, genotype errors, mutation recurrence, and other complications. Although full sequences yield the most granular haplogroup classifications, genotyping arrays can yield reliable calls, provided a reasonable number of phylogenetically informative variants has been assayed.

Briefly, haplogroup calling involves two steps. The program first builds an internal representation of the Y-chromosome phylogeny by reading its primary structure from (Newick-formatted) text and importing phylogenetically informative SNPs from the ISOGG database, affiliating each SNP with the appropriate node and growing the tree as necessary. It then traverses the tree for each individual, identifying for each the path of derived alleles leading to a haplogroup designation.

yHaplo is available for non-commercial use pursuant to the terms of the non-exclusive license agreement, LICENSE.txt. To learn more about the algorithm, please see our bioRxiv pre-print:

Poznik GD. 2016. Identifying Y-chromosome haplogroups in arbitrarily large samples 
of sequenced or genotyped men. bioRxiv doi: 10.1101/088716

And, to learn more about the software, please see the manual, yHaplo.manual.pdf.

Please note that yHaplo does not check for sex status; it assumes all samples are male.

Input

Phylogenetic data

input/

y.tree.primary.DATE.nwk : primary structure of the Y-chromosome tree
isogg.DATE.txt : phylogenetically informative SNPs
isogg.correct.*.txt : corrections to ISOGG data
isogg.omit.*.txt : SNPs to drop due to inconsistencies observed in test data
isogg.multiallelic.txt : physical coordinates of multiallelic sites to be excluded
representative.SNPs.*.txt : SNPs deemed representative of corresponding haplogroups

Supported genotype formats

.genos.txt : sample-major genotypes
- row 1: physical coordinates
- column 1: individual IDs
- cell (i, j): genotype for individual i at position j, encoded as a single character from the set { A, C, G, T, . }, with "." representing an unobserved value
.resid.txt : file with 23andMe research IDs in the first column
.vcf, .vcf.gz : snp-major VCF file
.vcf4 : snp-major pseudo-VCF. differences include:
- no "#" in header row
- fewer header columns
- GT values recorded as { A, C, G, T, . } rather than { 0, 1, . }

Code

Driver script

callHaplogroups.py : for an overiew of command-line options, issue the following command: callHaplogroups.py -h

Main classes

Tree : knows root, depth, haplogroup-to-node mappings, etc.; parses a Newick file to build primary tree; parses ISOGG table to add SNPs to nodes and grow tree; finds the derived path leading from the root to an individual
Node : element of the tree. knows parent, children, snps, etc. represents the branch that leads to it
SNP : knows position, ancestral and derived alleles, node, etc.
PlatformSNP : knows position and ablock index
Sample : knows an individual's genotypes and haplogroup
Customer : (subclass of Sample) has 23andMe metadata and genotypes from ablocks
Path : path through a tree; stores the next node to visit, a list of SNPs observed in the derived state, the most derived SNP observed, and the number of ancestral alleles encountered
Page : 23andMe content page labels
Config : container for parameters, command-line options, and filenames

Utilities

utils.py : shared utility functions

Auxiliary scripts

convert2genos.py : converts data to .genos.txt format
plotTree.py : plots a newick tree

lsamaha/yhaplo