Skip to content

Speed up SV annotation: move conservation bigWig scoring from VEP to pyBigWig #1657

Description

@davmlaw

🤖 Written by Claude

SV annotation runs can take hours / never finish. Benchmarking (GRCh37/RefSeq/VEP 116, real prod data) shows the bottleneck is not the gnomAD-SV overlap (+3s) but the four conservation bigWig --custom summary_stats=max annotations (phastCons/phyloP), whose cost scales with SV span length:

  • 1,486 SVs: baseline VEP 10.4s; +gnomAD 13.3s; +4 conservation bigwigs → timeout >290s
  • single bigwig track: 559 tiny INS = 5.6s; 200 large SVs (0.5–4.5Mb) = timeout >200s

Proposed fix: drop the 4 conservation --custom bigwig args from the SV VEP command and compute the same _max columns in a separate pyBigWig stage. A validated PoC (aligned-window decomposition) is bit-exact vs VEP and does the 200 large SVs in 10.2s (VEP never finished).

Full write-up, benchmark tables, window convention, code sketch and integration steps: claude/sv_pybigwig_plan.md.

Implementation to be tackled later.

Metadata

Metadata

Assignees

No one assigned

    Labels

    No labels
    No labels

    Type

    No type

    Fields

    No fields configured for issues without a type.

    Projects

    No projects

    Milestone

    No milestone

    Relationships

    None yet

    Development

    No branches or pull requests

    Issue actions