akt pca [OPTIONS] FILE

Performs principal component analysis on a BCF/VCF. Can also be used to project samples onto pre-calculated principal components from another cohort. Uses a randomised SVD by default for very fast computation. WGS data is far denser than required for a meaningful PCA, it is recommended you provide a thinned set of sites via the -R command.

Examples:

./akt pca multisample.bcf -R data/wgs.grch37.vcf.gz -O b -o pca.bcf > pca.txt

The file pca.txt contains

SAMPLE_ID0 P0 P1 P2 P3 P4
SAMPLE_ID1 P0 P1 P2 P3 P4
...

The bcf file pca.bcf contains

bcftools query -f "%INFO/WEIGHT\n" pca.bcf
pc00 pc01 pc02 pc03 pc04
pc10 pc11 pc12 pc13 pc14
...

First index is the site index and second which is the coefficient (loading) that can be used to project other samples onto these principal components. For example we could project a new set of samples onto these same PCs via:

./akt pca new_multisample.bcf -W pca.bcf > projections

akt kin [OPTIONS] FILE

Calculates kinship coefficients (and other related metrics) from multi-sample VCF/BCFs. Can be used to detect (closely) related or duplicated samples.

Run the kinship calculation by giving akt a multi-sample vcf/bcf file:

Example usage:

$ akt kin multisample.bcf -R data/wgs.grch37.vcf.gz -n 32 > kin.txt

This outputs the following seven column format:

ID1 ID2 IBD0 IBD1 IBD2 KINSHIP NSNP

akt relatives [OPTIONS] FILE

Takes the output from akt kin and detects/reconstructs pedigrees from the information. Can also flag duplicated samples and create lists of unrelated samples.

./akt relatives allibd -g > allrelatives

The output contains duplicates, families and relationship types.

grep ^Dup allrelatives
Dup0 Sample0
Dup0 Sample1
...
grep ^Fam allrelatives
Fam0 Sample2
Fam0 Sample3
...
...
grep ^Type allrelatives
Type Fam0 Sample2 Sample3 Parent/Child
...
grep ^Unrel allrelatives
Sample0
Sample2
...

The file out.allgraph can be viewed with gviz e.g. fdp out.allgraph -Tpng -O and the families can be viewed using e.g. dot out.Fam0.graph -Tpng -O. The parent child relations are also recorded in PLINK fam format in out.fam. If e.g. a sibling pair, is found the samples will appear in out.fam without parents. If the direction of the relationship can’t be determined e.g. for parent/child duos a random sample is assigned to be the parent in out.fam. The final column in the .fam file specifies how many potential parents the sample had.

Note that relatives is quite a aggressive in its pedigree search, and can make errors when founders are missing (for example a mother and two children). We can remove false pedigrees via a simple Mendel consistency check:

akt kin --force -M 1 test.bcf > kinship.txt
akt relatives kinship.txt
akt mendel -p out.fam test.bcf > mendel.txt
python ~/workspace/akt/scripts/check_pedigree.py -fam out.fam -m mendel.txt > corrected.fam

akt unrelated [OPTIONS] FILE

This takes the output from akt kin and creates a list of nominally unrelated individuals.

The algorithm has two options:

Repeat this i times, storing the largest unconnected set found. If the stochastic approach yields a larger unconnected set than the greedy approach then that is returned, else the greedy result is returned.

Note this maximal independent set problem is NP-hard.

akt pedphase [OPTIONS] FILE

This performs simple Mendelian phase-by-transmission, with the novelty that FORMAT/PS will be handled sensibly.

Note: this does not do anything clever with complex pedigrees, parental haplotypes are inferred as the transmitted/untransmitted haplotypes of the first listed child. For clever complex pedigree phasing, use Merlin, HAPI or duohmm (which one depends on your use case).