I read a lecture notes about mutations, what kind of algorithms are there to detect mutations?

How do people know if the gene is mutated or whether it's a sequencing error?

I saw this which is related, but I am not sure how to work with CIGAR, is it 100% accurate? What's the underline mechanism to detect mutation? Is there a way to predict what the mutation will cause.


I'll follow up to the great answer from Kamil S Jaron:

Regarding predicting what the variant ("mutation" is a very loaded term) will do, there are a variety of tools. Chief among these are annovar and VEP. The general idea behind these is to classify the variants according to their overlap with genes, which codons they change (if any), how big that change is (e.g., changes in charge are more likely detrimental) and so on. One could also consider conservation, since if a position is highly conserved then changes in it are more likely to be detrimental.

If you really want to predict how a variant will change a protein's function then that usually requires prior knowledge about the proteins in question. Eventually someone will use machine learning to cull the literature and provide good predictions, but I haven't seen that yet.

  • $\begingroup$ Nice summary, to add, PhastCons is the standard for conservation scores, although not the best as the Sipel lab has many newer tools alternatives and GERP++ is also better IMO. Also if you're looking at just a few individual loci, nothing beats a stare at a genome browser like UCSC $\endgroup$ – Chris_Rands Jun 11 '17 at 16:47

Part 1 : how to detect mutations

The keywords you are searching for are "variant calling". Basically you have to map sequencing reads to a reference genome (or gene) and then estimate for each position of the genome if the observed difference of mapped reads and the reference is more likely a sequencing error or a mutation (in genomic glossary - variant).

Popular tools for variant calling are GATK, FreeBayes or bcftools (previously part as Samtools package).

The question you linked asks for quick alternatives to simply looking for variants. Indeed, you can just visualise the mapped reads to the reference sequence and see if the variant is there or not. CIGAR is just a notation of read alignment used in sam files (files with mapped reads), you can find good explanation of CIGAR strings here.

The follow-up about "How to estimate an effect of mutation" is in @DevonRyan 's awesome answer.


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