TRGT-denovo

Calling de novo tandem repeat mutations

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TRGT-denovo is a companion tool of TRGT (Tandem Repeat Genotyper) that further annotates TRGT genotyping using additional read-level information from samples, specifically for identifying de novo tandem repeat mutations in parent-child trios and 1-to-1 comparisons using PacBio Hifi data.

Preprint: TRGT-denovo: accurate detection of de novo tandem repeat mutations

Developers: Tom Mokveld, Egor Dolzhenko

Early version warning

Please note that TRGT-denovo is still in early development and is subject to significant changes that can affect anything from input / output file formats to program behavior.

Availability

• Latest release with binary

To build TRGT-denovo you need a working C compiler: it was tested on Linux with Clang 13.0.0 & GCC 11.3.0 and on Mac OSX (M1) with Clang 15.0.7 & GCC 14.0.0.

Documentation

• Getting started
• Output format
• Interpretation
• Command-line interface

Need help?

If you notice any missing features, bugs, or need assistance with analyzing the output of TRGT-denovo, please don't hesitate to open a GitHub issue.

Support information

TRGT-denovo is a pre-release software intended for research use only and not for use in diagnostic procedures. While efforts have been made to ensure that TRGT-denovo lives up to the quality that PacBio strives for, we make no warranty regarding this software.

As TRGT-denovo is not covered by any service level agreement or the like, please do not contact a PacBio Field Applications Scientists or PacBio Customer Service for assistance with any TRGT-denovo release. Please report all issues through GitHub instead. We make no warranty that any such issue will be addressed, to any extent or within any time frame.

Changelog

• 0.2.1

  • Duo and trio mode now always output entries regardless of error status (e.g., missing genotyping, skip because of quick mode).
  • Add denovo_status analog to duo mode.

• 0.2.0

  • Implemented duo mode, it is now possible to perform 1-to-1 sample comparisons, following the same principles as in trio analysis. This can be done using the subcommand trgt-denovo duo.
  • Implemented the --quick flag. Users can now specify --quick AL[,<fraction>] to skip loci where allele lengths are similar between parents and child or between two samples. If no fraction is specified (or fraction is 0), it checks for exact matches. If a fraction is specified, it checks if the relative difference is within the given tolerance.
  • Added a Jupyter notebook in scripts/python/trio_analysis.ipynb to describe a simple trio analysis to do de novo candidate selection.

• 0.1.3

  • Changes to TRGT-denovo output:
    • Truncate zeros in output.
    • Report TRGT allele lengths observed in each family member as sample_AL.
    • Renamed TRGT motif counts from sample_motif_counts to sample_MC.
    • Report the overlap coverage; this is the reciprocal of the de novo coverage, i.e., the number of reads in per allele in the parent that overlap compared to the child data.
  • Lower memory footprint: Better memory management, significantly reduces memory usage with large repeat catalogs.
  • Improved IO error handling.

• 0.1.2

  • With the recent changes to TRGT, within-sample partitioning is now alignment-free in TRGT-denovo. An optional parameter has been added to still use alignment (--partition-by-aln).
  • Homozygous alleles are no longer collapsed: de novo evidence will now always gathered and be specific to a single allele only.

• 0.1.1

  • Add cli parameter to set aligner penalties.
  • Document the codebase.
  • Update documentation to include interpretation of generated output.

Ongoing work

• Add downstream scripts to:
  • further annotate TRGT-denovo output with population specific data, e.g., outlier detection, is a particular allele an outlier with respect to a population.
  • select candidate de novo calls through classification.
  • show an example of duo based analysis to detect sites of interest.
• Haplotype matching across samples using flanking variation.

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