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Germline copy number variant discovery (CNVs)

Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie
edited January 9 in Best Practices Workflows

Purpose

Identify germline copy number variants.


Diagram is not available


Reference implementation is not available


This workflow is in development; detailed documentation will be made available when the workflow is considered fully released.

Post edited by Geraldine_VdAuwera on
Tagged:

Comments

  • mglclinicalmglclinical USAMember
    edited February 5

    Hi @Geraldine_VdAuwera ,

    I am under the impression that GATK4 can be used to detect SVs (structural variations) or CNVs (copy number variations) in germline samples from Exome sequencing. Please correct me if my understand is correct or not.

    Is there a GATK4's reference implementation of CNV detection in germline samples from Exome Sequencing ?

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie

    Hi @mglclinical, yes we have pipelines in development for this. The germline CNV pipeline (for which this doc is a placeholder) is close to being in a releasable state. The SV pipeline is going to take a few more months, I believe.

  • Hello,
    I was hoping to run the germline CNV pipeline, but I got stuck at the DetermineGermlineContigPloidy step. I am not sure what is the best way to generate the inferred ploidy model for CASE runs.
    Thanks in advance!

    Issue · Github
    by Sheila

    Issue Number
    2988
    State
    closed
    Last Updated
    Assignee
    Array
    Closed By
    sooheelee
  • SheilaSheila Broad InstituteMember, Broadie, Moderator

    @KMS_Meltzy
    Hi,

    Let me have someone on the team get back to you soon.

    -Sheila

  • shleeshlee CambridgeMember, Broadie, Moderator

    Hi @KMS_Meltzy,

    This workflow is under development and I am not altogether familiar with it. I think you might find https://github.com/broadinstitute/gatk/tree/master/scripts/cnv_wdl/germline helpful. Note that some of the workflow components are shared in a separate script called cnv_common_tasks.wdl.

    We have some germline CNV resource files available in the GATK Resource Bundle, e.g grch37_germline_CN_priors.tsv that were used with the GATK4.beta version of the tools.

  • hexyhexy ChinaMember

    Hi @Geraldine_VdAuwera, your slides showed that GATK4 can be used to detect germline CNV, but I cannot find the best practice doc. Would you pelease tell me where to find this?

  • SheilaSheila Broad InstituteMember, Broadie, Moderator

    @hexy
    Hi,

    The germline CNV documentation is not yet ready. We hope to have some out within a month or two. If you search the forum for "germline CNV" you should get some helpful threads/docs.

    -Sheila

  • hexyhexy ChinaMember

    @Sheila
    Hi, thanks! Hope to see that soon and would you please upload the test data of GATK4 to the ftp server?

  • SheilaSheila Broad InstituteMember, Broadie, Moderator

    @hexy
    Hi,

    would you please upload the test data of GATK4 to the ftp server?

    I am not sure which test data you are referring to?

    -Sheila

  • mglclinicalmglclinical USAMember

    Hi @Geraldine_VdAuwera and @Sheila ,

    I want to ask a question on GATK4's ability on detecting SVs or CNVs (copy number variations) in germline samples. I know that the best practices for this task are still under development. And my question is :

    We have a cell line that contains a single exon deletion on MECP2 gene. MLPA is used to validate this single exon deletion. This cell line is exome sequenced and analyzed by tools like xhmm & the Single exon deletion is not detected. I guess xhmm cannot detect this deletion because my deletion is just in 1 exon (or) because my sample size was too small (11 samples).

    Does GATK’s germline-CNV detection tool suffer the same problem ?

    Thanks,
    mglclinical

  • SheilaSheila Broad InstituteMember, Broadie, Moderator

    @mglclinical
    Hi mglclinical,

    I know the tools are still in beta, but the team has said our workflow performs better than xhmm :smile:

    That said, perhaps it would be nice if you could test the workflow out yourself and report back to us. This thread will help with some details..also another user has reported our workflow performing well. Also, you may find the poster presented at AACR helpful here.

    -Sheila

  • stefstefstefstef Member
    edited June 12

    Hi guys,
    Just a quick question - if I just wanted to test out gCNVs, do I need to have run BSQR on my bam files?

    Thanks

    Stef

    Post edited by stefstef on
  • shleeshlee CambridgeMember, Broadie, Moderator

    Hi @stefstef,

    The quick answer is no. gCNV coverage collection is the same as for the somatic workflow. In terms of qualities, CollectReadCounts only takes into consideration mapping quality. The read filters are

    MappedReadFilter, MappingQualityReadFilter, NonZeroReferenceLengthAlignmentReadFilter, NotDuplicateReadFilter, WellformedReadFilter

    You can read about each in the Tool Docs, under Read Filters.

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