Genotyping diploid organisms from Sanger AB1 files
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5.7 years ago
ognjen011 ▴ 290

Hi!

I am trying to automate variant calling on human short exons sequenced with Sanger method. I have the ab1 files, and I want to automate the process for clinical geneticists. The program should be free, I understand that is a huge limitation. Also, it needs to register INDELS in addition to SNPs.

I tried working with tracy, and it works fine but fails silently, and fails to index the reference (I have opened github issues for that). TraceTuner doesn't seem to do anything when I use the -het flag, it just outputs the single consensus fasta (no heterozygous calls). They currently work on Sequencher trial version, but this version doesn't do variant calling. Baseling also doesn't mention automated heterozygous calls. Although there are mentions of writing in ambiguous bases which could be a code for a heterozygous, this becomes a problem for INDELs.

Is there a free resource that somebody uses successfully for human diploid data variant calling? Thanks all!

sanger variant-calling • 1.7k views
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Maybe Phred/Phrap can help here, but I am not sure. See this paper.

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When I worked on Sanger data I used Phred/Phrap/Polyphred, and it was probably the best tool around. If you are using the results in clinical setting you might investigate the issues brought forward by genomax with your clinical colleagues.

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While I understand a desire to use a free solution have you checked applicable local administrative policy for this. You may need (or be required) to use a validated/approved (and thus perhaps not free) application, if the data is going to be used for patient diagnostics.

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This is a very valid concern. If all fails, it will be a nice way to screen or double-check.

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5.7 years ago
trausch ★ 1.9k

The problem with the indexing in tracy was the leading whitespace, right? If there is any other issue please let us know.

tracy decompose -f align -o out -a homo_sapiens -g Homo_sapiens.GRCh38.dna.primary_assembly.fa.gz trace.ab1

Tracy is still work-in-progress so any feedback is very welcome. The above command generates alignments, decomposes InDels, annotates variants with rs identifiers and generates a BCF file for downstream processing. The reference genome index files can be downloaded here and please let us know if your species of interest is missing.

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