Usage:
nimpress [options] <scoredef> <genotypes.vcf>
nimpress (-h | --help)
nimpress --version
Options:
-h --help Show this screen.
--version Show version.
--cov=<path> Path to a BED file supplying genome regions that have been
genotyped in the genotypes.vcf file.
--imp-locus=<m> Imputation to apply for whole loci which are either not
in the sequenced BED regions, or fail (QUAL flag or too
many samples with missing genotype). Valid values are ps,
homref, fail [default: ps].
--imp-sample=<m> Imputation to apply for an individual sample with missing
genotype. Valid values are ps, homref, fail, int_fail,
int_ps [default: int_ps].
--maxmis=<f> Maximum fraction of samples with missing genotypes allowed
at a locus. Loci containing more than this fraction of
samples missing will be considered bad, and have all
genotypes (even non-missing ones) imputed [default: 0.05].
--mincs=<n> Minimum number of genotypes.vcf samples without missing
genotype at a locus for this locus to be eligible for
internal imputation [default: 100].
--afmisp=<f> p-value threshold for warning about allele frequency
mismatch between the polygenic score and the supplied
cohort [default: 0.001].
Imputation methods:
ps Impute with dosage based on the polygenic score effect allele
frequency.
homref Impute to homozygous reference genotype.
fail Do not impute, but fail. Failed samples will have a score of "nan"
int_ps Impute with dosage calculated from non-missing samples in the
cohort. At least --mincs non-missing samples must be available for
this method to be used, else it will fall back to ps.
int_fail Impute with dosage calculated from non-missing samples in the
cohort. At least --mincs non-missing samples must be available for
this method to be used, else it will fall back to fail.
At the moment a placeholder format is used for polygenic scores. This is likely to change rapidly.
The placeholder format is a text file:
<name>
<description>
<citation>
<genome version>
<offset>
<chrom>\t<pos>\t<refallele>\t<effallele>\t<beta>\t<effallele_af>
<chrom>\t<pos>\t<refallele>\t<effallele>\t<beta>\t<effallele_af>
...
The first four header records (name, description, citation, and genome version) are free text, the last header record (offset) is a string representation of a floating point number.
Lines following the header define the polygenic score alleles and coefficients, one line per allele, with fields separated by tabs. is the polygenic score coefficient associated with a single alternate allele. <effallele_af> is the effect allele frequency in the polygenic score derivation cohort, 0 < effallele_af <= 1.
The polygenic score for sample i is calculated as:
score_i = sum_{j=1..m}(beta_j*dosage_ij)/m + offset
where offset is the offset as given in the header, beta_j is the beta for row j of the
polygenic score definition, dosage_ij is the dosage of the row j effect allele in sample i,
and m is the number of alleles (rows) in the polygenic score. dosage_ij may be imputed.
It's not uncommon for the reference allele to also be the effect allele; in this case set
<effallele> to equal <refallele>.
- Currently diploid-specific.
- Does not fully handle multi-allelic risk loci (specifically, loci at which more than one allele has a nonzero beta are not supported)
- Performs only simple allele matching. As the representation of some variants in VCF is not unique, this may lead to polygenic score variants being imputed even if they are present in the VCF.
- Option to calculate soft PS based on genotype likelihoods (VCF PL field)
- Full multi-allelic locus handling (will require imputation to a distribution over dosages of all alleles, instead of just the effect allele)
- Smarter variant matching.