annotate PsiCLASS-1.0.2/samtools-0.1.19/bcftools/README @ 0:903fc43d6227 draft default tip

Uploaded

The view command of bcftools calls variants, tests Hardy-Weinberg
equilibrium (HWE), tests allele balances and estimates allele frequency.

This command calls a site as a potential variant if P(ref|D,F) is below
0.9 (controlled by the -p option), where D is data and F is the prior
allele frequency spectrum (AFS).

The view command performs two types of allele balance tests, both based
on Fisher's exact test for 2x2 contingency tables with the row variable
being reference allele or not. In the first table, the column variable
is strand. Two-tail P-value is taken. We test if variant bases tend to
come from one strand. In the second table, the column variable is
whether a base appears in the first or the last 11bp of the read.
One-tail P-value is taken. We test if variant bases tend to occur
towards the end of reads, which is usually an indication of
misalignment.

Site allele frequency is estimated in two ways. In the first way, the
frequency is esimated as \argmax_f P(D|f) under the assumption of
HWE. Prior AFS is not used. In the second way, the frequency is
estimated as the posterior expectation of allele counts \sum_k
kP(k|D,F), dividied by the total number of haplotypes. HWE is not
assumed, but the estimate depends on the prior AFS. The two estimates
largely agree when the signal is strong, but may differ greatly on weak
sites as in this case, the prior plays an important role.

To test HWE, we calculate the posterior distribution of genotypes
(ref-hom, het and alt-hom). Chi-square test is performed. It is worth
noting that the model used here is prior dependent and assumes HWE,
which is different from both models for allele frequency estimate. The
new model actually yields a third estimate of site allele frequency.

The estimate allele frequency spectrum is printed to stderr per 64k
sites. The estimate is in fact only the first round of a EM
procedure. The second model (not the model for HWE testing) is used to
estimate the AFS.