tsoppy input standardization - 7. Run-wide variant summary

[danielvo]

Inputs considered so far:

• Dragen TSO500 analysis pipeline v. 2.6.2
  • the information below is based on output generated for samples sequenced with TSO500 assay version 2, but the current
  • unclear: is the Dragen server version a factor?
    • OUS assumes it does not, and both OUS and UNN use the same Dragen server version.
      • It looks like both assay v1 and assay v2 samples can now be analyzed with the same Dragen software.
    • Dragen server version [07.021.624.]3.11.2 was used when generating the output referenced in the text below
    • UNN utilizes the same Dragen server version and Dragen TSO500 analysis pipeline version
    • unclear: When analyzing samples with ICA (Illumina Cconnected Analysis), can one pick exactly the same Dragen server version and TSO500 pipeline version?
  • unclear: can the analysis output structure vary based on the sample sheet content/format choices?
    • different Pair_ID and Sample_ID values were used when generating the output referenced in the text below
    • we should aim to standardize the sample sheets across InPreD nodes either way
• Local App version 2.2.0.12
  • the sample sheet content/format (e.g., the Pair_ID value choice) can impact the analysis output structure
    • different Pair_ID and Sample_ID values were used when generating the output referenced in the text below

7. Run-wide variant summary

The purpose of this tool is to provide an overview of selected variant calls and metrics across all samples in a given sequencing run. TSOPPI currently summarizes Local App-reported variants and metrics, not calls and metric values that made it through the post-processing (if there is an interest in creating summaries of post-processing results, creating a new/additional tool would likely be the way to go - Jaime and Jean-Marc already started gathering some of the post-processing output in an HTML file, which could perhaps be further extended).
TSOPPI parses *_CombinedVariantOutput.tsv files within a given Local App run output directory, extracting selected pieces of information and re-formatting them into a table with one sample per line and one variant type/metric per column (omitting small variant calls, which are typically too numerous for being reasonably listed in a simple and still useful table). The *_CombinedVariantOutput.tsv files are organized in a fashion similar to the metrics files (which are discussed in #14), with distinct sections that are introduced by dedicated labels and contain tables with unique layouts (with respect to the number of columns and the type of included information).

7.1 Input files

Dragen TSO500 2.6.2:

• file path: Logs_Intermediates/CombinedVariantOutput/<sample_ID>/<sample_ID>_CombinedVariantOutput.tsv

Local App 2.2.0.12:

• file path: Logs_Intermediates/CombinedVariantOutput/<sample_ID>/<sample_ID>_CombinedVariantOutput.tsv

Both pipelines utilize the same output file paths/names.

The sections of interest:

• The following sections are shared between both pipelines and have consistent labels and structure:

  • [TMB]: Values related to Tumor Mutational Burden calculations
  • [MSI]: Values related to Micro-Satellite Instability
  • [Splice Variants]: Details about splice variant calls that pass all filters
  • [Fusions]: Details about fusion calls that pass all filters

• The following sections are related, but their labels and structure differ between the pipelines:

  • Local App's [Gene Amplification] section informs about CNV gains only; Dragen's [Copy Number Variants] section reports about CNV gains and losses, while its [Loss of Heterozygosity] section informs about LoH genes (the latter section has no equivalent in the Local App output)

• The following sections are unique to the Dragen pipeline:

• [GIS]: Values related to Genomic Instability Score (includes tumor content and ploidy)

• [Large Rearrangements]: Details about BRCA 1/2 rearrangements that pass all filters

7.2. Variant summary usage in tsoppy modules

Only the variant summary creation module.

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We can have a look at the variant summary creation once we are done with metrics processing. The input standardization process here will be very similar.