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Strategy low coverage ancient DNA- HaplotypeCaller

Has any staff member attempted to process low coverage ancient DNA (avg coverage <1) with low endogenous content using HaplotypeCaller. If so, what settings are suggested so as to minimize reference bias at very low coverage loci.

I am not sure if HaplotypeCaller can compete with callers specifically designed to deal with ancient DNA. Perhaps it can, I personally have not conducted comparison tests. Haak, 2015 suggested a random draw method.

Best Answers


  • Besides setting --minPruning and --minDanglingBranchLength to 1, so as to not throw out any branch of the graph that has less than 2 reads during realignment, since default minPruning is 2, and since length of a dangling branch to attempt recovery is 4 by default, is there anything else that can be done.

    What about lowering the emit confidence threshold, and call confidence thresholds also. Any suggested values lower than default? Or is this unnecessary.

    Also was wondering if the false positives will be slightly higher or significantly higher using the settings in my 1st paragraph. I did not see a comparison study. I can live with an increase of FP of about 10%.


  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin
    I believe @alexpe has experience with ancient DNA, and has in fact authored a pipeline that could be relevant. Perhaps he may join in this discussion if he's available.
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