What Coverage allele-fraction threshold to use?
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3.7 years ago

I UV mutated a haploid algae genome and want to view the variants in the bam file on IGV. What Coverage allele-fraction threshold should I use to look at variants?

allele-fraction snps • 1.8k views
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Depends on your sequencing coverage and desired False Discovery Rate.

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The sequencing coverage is >200x

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At each genomic position you have a specific coverage, say X. Y out of X reads may support an alternative variant, X - Y - reference. You need to perform a statistical test (there are tens of types of stat tests, more and less sophisticated) how unusual is to see Y reads given the error rate of your sequencing machine of Z. You can simply use a Binomial test. Then you get a bunch of p-values. You put these p-values into some FDR correction procedure and get your approximate threshold.

This procedure has its drawbacks and is not exactly correct, but may be useful.

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Can you point me to some statistical tests?

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For example, your probability of error as a substitution is 0.1% (in Illumina machines it is a very small number). You see 5 nucleotides A and 195 nucleotides B at some position. You apply Binomial test and find a p-value ( https://en.wikipedia.org/wiki/Binomial_test )

This is the simplest test, then people model errors with more efficient regression models with various link functions, but you may start with Binomial.

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