David Poznik, 23andMe
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 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 preprint:
Poznik GD. 2016. Identifying Y-chromosome haplogroups in arbitrarily large samples
of sequenced or genotyped men. bioRxiv doi: 10.1101/088716
To learn more about the software, please see the manual, yhaplo_manual.pdf
.
For an overiew of command-line options, install the package and run yhaplo --help
.
To install:
git clone git@github.com:23andMe/yhaplo.git
cd yhaplo
pip install --editable .
To update:
cd /path/to/yhaplo
git pull # Update code
pip install --editable . # Update version number
To include optional dependencies for various features:
pip install --editable .[vcf]
Enables running on VCF/BCF inputpip install --editable .[plot]
Enables tree plottingpip install --editable .[dev]
Includes all optional dependencies, as well as development tools (e.g.,pytest
)
To install multiple optional features, use a comma-separated list. For example:
pip install --editable .[vcf,plot]
To run on example text data:
yhaplo --example_text
The --example_text
option tells yhaplo
to run on a subset of 1000 Genomes data
in sample-major text format. It also sets the --all_aux_output
flag
to produce all auxiliary output.
Similarly, to run on example VCF data:
yhaplo --example_vcf
To run unit tests:
make test
Please note the following caveats before running yhaplo
:
yhaplo
does not check for sex status; it assumes all individuals are male.yhaplo
expects SNP coordinates consistent with the hg19/GRCh37 reference assembly.yhaplo
expects data at a reasonable number of ISOGG SNPs. This assumption is violated by:- Variants-only sequence data
- Very low-coverage sequencing
- Genotyping arrays with few Y-chromosome probes
If, for a given individual, yhaplo
observes no derived alleles at ISOGG SNPs on the upper
branches of the Y-chromosome phylogeny, it will call the individual haplogroup "A,"
since all human Y-chromosome lineages are technically sublineages of A.
Before concluding that the individual sample belongs to paragroup A (which
includes haplogroups A00, A0, A1a, and A1b1), run with the --anc_snps
option, and check the
auxiliary output for ancestral alleles at haplogroup-BT SNPs. If you do not see any,
your data set probably violates one or more of the assumptions listed above.
In particular, "variants-only" VCF files restrict to SNPs at which alternative alleles
were observed, but ref/alt status is unimportant to yhaplo
. What is important is
ancestral/derived status. The reference sequence contains many derived alleles,
and yhaplo
will not be happy if you discard these valuable data. So please emit all
confident sites when calling variants. To limit file size, you could safely restrict to
positions in output/isogg.snps.unique.DATE.txt
, as these are the only SNPs yhaplo
considers. To generate this file, just run yhaplo
with no arguments.
The following input file types are supported:
- Indexed BCF:
.bcf
,.bcf.csi
- Indexed VCF:
.vcf.gz
,.vcf.gz.tbi
- Sample-major text:
.genos.txt
or.genos.txt.gz
- Row 0: Physical coordinates (GRCh37)
- Column 0: Individual identifiers
- Cell (i, j): Genotype for individual i at position j.
Values include {"A", "C", "G", "T", "."}, with "." indicating an unobserved value.
In addition, the API supports running on a mapping of individual identifiers to 23andMe ablocks.
All output file formats are described in detail in yhaplo_manual.pdf
.
The two primary output files are:
log.project_name.txt
Log file containing details of the runhaplogroups.project_name.txt
Haplogroup calls. The 4 columns are:- ID
- Haplogroup short form, with the name of a SNP observed in the derived state
- Haplogroup short form, with the name of a representative SNP
- Haplogroup long form, using Y-Chromosome Consortium nomenclature
yhaplo
also produces a number of SNP tables, tree files, and auxiliary output files.
Please see yhaplo_manual.pdf
and yhaplo --help
for details.
See yhaplo/api/call_haplogroups.py
.
The main command-line entry-point is yhaplo
.
Additional commands include:
yhaplo_convert_to_genos
yhaplo_plot_tree
The primary structure of the Y-chromosome tree is stored in
yhaplo/data/tree/y.tree.primary.DATE.nwk
.
Variant metadata are stored in yhaplo/data/variants/
:
isogg.DATE.txt
Phylogenetically informative SNPs scraped directly from the ISOGG website.
yhaplo
resolves errors and formatting inconsistencies and emits cleaned versions:isogg.snps.cleaned.DATE.txt
,isogg.snps.unique.DATE.txt
.
Seeyhaplo_manual.pdf
for details.isogg.correct.*.txt
Corrections to ISOGG dataisogg.multiallelic.txt
Physical coordinates of multiallelic sites to be excludedisogg.omit.*.txt
SNPs to drop due to inconsistencies observed in test dataisogg.split.txt
Not currently usedpreferred.snp_names.txt
List of preferred SNP namesrepresentative.SNPs.*.txt
SNPs deemed representative of corresponding haplogroups
The Tree
class is defined in tree.py
. It:
- 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
- Knows root, depth, haplogroup-to-node mappings, etc.
The Node
class is defined in node.py
. It:
- Represents a phylogenetic branch
- Knows parent, children, SNPs, etc.
The SNP
class and related classes are defined in snp.py
:
SNP
Knows position, ancestral and derived alleles, node, etc.
The Sample
class and its subclasses are defined in sample.py
:
Sample
Knows genotypes and haplogroup of an individualTextSample
Subclass for sample-major text inputVCFSample
Subclass for VCF/BCF input
The Path
class is defined in path.py
. It represents a ath through a tree and stores:
- The next node to visit
- A list of SNPs observed in the derived state
- The most derived SNP observed
- The number of ancestral alleles encountered
The Config
class is defined in config.py
.
It is a container for parameters, command-line options, and filenames.