Difference between revisions of "Genotype Likelihood based Allele Frequency"

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(Created page with '=== Introduction === Allele frequencies are an important statistic in the study of genetic variants. This page details EM algorithms to estimate allele frequencies from genoty…')
 
(Introduction)
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=== Introduction ===
 
=== Introduction ===
  
Allele frequencies are an important statistic in the study of genetic variants.  This page details EM algorithms to estimate allele frequencies from genotype likelihoods in NGS data.
+
Allele frequency is an important statistic in the study of genetic variants.  This page details EM algorithms to estimate allele frequencies from genotype likelihoods in NGS data.
  
 
=== Estimation of Genotype Frequencies without assuming HWE ===
 
=== Estimation of Genotype Frequencies without assuming HWE ===

Revision as of 12:30, 4 June 2013

Introduction

Allele frequency is an important statistic in the study of genetic variants. This page details EM algorithms to estimate allele frequencies from genotype likelihoods in NGS data.

Estimation of Genotype Frequencies without assuming HWE

This is an EM algorithm to estimate the genotype frequencies without assuming HWE. The posterior probability of the genotype given the reads for individual k (R_k) for the lth iteration is given by:


  \begin{align}
P(G_{i,j}|R_{k})^{(l)}=\frac{P(R_{k}|G_{i,j})P(G_{i,j})^{(l-1)}}{\sum_{(i,j)}{P(R_{k}|G_{i,j})P(G_{i,j})^{(l-1)}}}
   \end{align}

where G_{i,j} denotes the genotype composed of alleles i and j. k indexes the individuals from 1 to N. The initial genotype probability is given by:


  \begin{align}
P(G_{i,j})^{(0)} = f_{i,j}^{(0)} = \frac{2}{n(n+1)} 
   \end{align}

The E step equates the expectation of the genotype G_{i,j} for individual k as:


  \begin{align}
E[G_{i,j}|R_{k}]^{(l)}=P(G_{i,j}|R_{k})^{(l)}
   \end{align}

The M step estimates the genotype frequency using the individual expected genotype counts:


  \begin{align}
P(G_{i,j})^{(l)} = f_{i,j}^{(l)} = \frac{1}{N}\sum_{k}{E[G_{i,j}|R_{k}]}^{(l)}
   \end{align}

This is repeated till the appropriate convergence criteria is achieved.

Estimation of Genotype Frequencies assuming HWE

In order to estimate allele frequencies under HWE assumption, the E step estimates the individual expected posterior allele count for each individual.


  \begin{align}
E[I|R_{k}]^{(l)}=P(G_{i,i}|R_{k})^{(l)} + 0.5P(G_{i,j}|R_{k})^{(l)}
   \end{align}

In the M step, the posterior genotype frequencies are derived from the computed genotype allele frequencies obtained in the E step assuming HWE.


  \begin{align}
P(I)^{(l)} =  \frac{1}{N}\sum_{k}{E[I|R_{k}]}^{(l)}
   \end{align}


  P(G_{i,j})^{(l)}  = \begin{cases}
	  	                     (P(I)^{(l)})^2, &  \text{if }i=j \\ 
       						    	2P(I)^{(l)}P(J)^{(l)},  & \text{if }i \ne j 
                                    \end{cases}

This is repeated till the appropriate convergence criteria is achieved.

Used in

Hardy-Weinberg Likelihood Test statistic and Inbreeding Coefficient

Derivation

Adrian with much help from Hyun.

Maintained by

This page is maintained by Adrian.