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Graph-based cancer genome karyotyping and structural-variant analysis tool

Tests

SKYPE generates the following results.

  • A Circos plot showing observed and reconstructed copy number together with rearrangement junctions, indels, amplicons, and neotelomeres
  • A Virtual SKY diagram showing depth-weighted combinations of reconstructed cancer chromosome paths
  • An ISCN-style karyotype summary and copy-number-weighted structural-variant results

SKYPE implements the following steps to generate these results.

  • Derive rearrangement junctions from contig/unitig alignments, or import them from a supported VCF
  • Classify contig segments by their mutational role and prune noisy or unnecessary segments
  • Compress contigs around their most significant terminal nodes (NClose)
  • Build a breakend graph by connecting NClose and telomere nodes
  • Find candidate telomere-to-telomere paths and circular components in the breakend graph
  • Recover full chromosome paths with normal reference segments
  • Estimate the copy number of each path using non-negative least squares
  • Visualize the reconstructed karyotype and report copy-number-weighted variants

Results

All files below are written to the SKYPE output directory.

Stage Output Description
30_virtual_sky.py virtual_sky.png, virtual_sky.pdf Virtual SKY diagram of reconstructed chromosome paths, colored by chromosome of origin and labeled with normalized copy number.
30_virtual_sky.py karyotype.txt Tab-separated ISCN-style karyotype labels and their normalized depth (N).
31_depth_analysis.py total_cov.png, total_cov.pdf Circos view of observed and reconstructed chromosome depth, with copy-number-weighted breakends, inversions, indels, amplicons, and neotelomeres.
31_depth_analysis.py SV_call_result.vcf Structural-variant calls (BND, INV, DEL, and DUP) with normalized copy-number support. Produced in assembly-input modes.
31_depth_analysis.py SKYPE_result.bed Simplified BED report of breakends, deletions, duplications, centromere fragments, amplicons, and virtual inversions. Produced in assembly-input modes.
31_depth_analysis.py SV_benchmark_result.vcf Copy-number-annotated copy of the input VCF. Produced only in VCF input mode instead of SV_call_result.vcf and SKYPE_result.bed.

The unsuffixed result files are always generated. Karyotype mode also generates _filter and _cluster versions of the Virtual SKY, karyotype, Circos, VCF, and BED results. Variant mode and VCF input mode generate only the unsuffixed versions.

Running SKYPE

Run SKYPE through the ACCtools pipeline, which prepares the assembly, alignments, depth data, reference resources, and stage arguments required by SKYPE.

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Specific graph-based Karyotype Profiling tool for cancer cell line

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