GATK中如何计算Inbreeding coefficient(近交系数)

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关于近交系数是什么的定义,除了英文资料,中文上也给出了清晰的定义,这里引用一下:

近交系数(inbreeding coefficient)是指根据近亲交配的世代数,将基因的纯化程度用百分数来表示即为近交系数,也指个体由于近交而造成异质基因减少时,同质基因或纯合子所占的百分比也叫近交系数,普遍以F或f来表示。

GATK近交系数的计算程序在github上可以找到:AS_InbreedingCoeff.java

代码不短,但计算很简单,我主要说展示一下这个计算的核心部分并在代码中做些注释,如下:

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protected double calculateIC(final VariantContext vc, final Allele altAllele) {
final int AN = vc.getCalledChrCount();
final double altAF;
final double hetCount = heterozygosityUtils.getHetCount(vc, altAllele);
final double F;
//shortcut to get a value closer to the non-alleleSpecific value for bialleleics
if (vc.isBiallelic()) {
double refAC = heterozygosityUtils.getAlleleCount(vc, vc.getReference());
double altAC = heterozygosityUtils.getAlleleCount(vc, altAllele);
double refAF = refAC/(altAC+refAC);
altAF = 1 - refAF;
F = 1.0 - (hetCount / (2.0 * refAF * altAF * (double) heterozygosityUtils.getSampleCount())); // inbreeding coefficient
} else {
//compare number of hets for this allele (and any other second allele) with the expectation based on AFs
//derive the altAF from the likelihoods to account for any accumulation of fractional counts from non-primary likelihoods,
//e.g. for a GQ10 variant, the probability of the call will be ~0.9 and the second best call will be ~0.1 so adding up those 0.1s for het counts can dramatically change the AF compared with integer counts
altAF = heterozygosityUtils.getAlleleCount(vc, altAllele)/ (double) AN;
// 计算inbreeding coefficient
F = 1.0 - (hetCount / (2.0 * (1 - altAF) * altAF * (double) heterozygosityUtils.getSampleCount())); // heterozygosityUtils.getSampleCount() 获取总样本数
}
return F;
}

总的来说,是利用哈迪温伯格定律来计算的。 1.0 - (hetCount / (2.0 (1 - altAF) altAF(double)N ,N是人数。这个值给出的是期望的杂合变异的个数。所以参数F说的就是”实际的hetCount”除以”期望的hetCount”再与1.0取差。当F值越接近0,就意味着实际的hetCount与理论的hetCount越接近。