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Talos

Talos is a scalable, open-source variant prioritisation tool designed to support automated reanalysis of genomic data in rare disease. It identifies candidate causative variants in known disease genes by integrating static annotations (e.g. population frequency, predicted consequence) with dynamic knowledge sources such as ClinVar and PanelApp Australia. Talos applies a set of configurable, rule-based logic modules aligned with ACMG/AMP criteria and prioritises variants consistent with expected mode of inheritance and, optionally, patient phenotype.

While Talos can be used for one-off reanalysis of individual families or cohorts, its core design is optimised for routine, cohort-scale reanalysis. By comparing current annotations with prior results, Talos highlights variants that have become reportable due to newly available evidence — such as new gene–disease or variant–disease relationships — since the last analysis cycle.

A full description of the method and its validation in large clinical and research cohorts is available in our preprint: medRxiv 2025.05.19.25327921.

Note - whether you are a new Talos user, or have an implementation already, we encourage you to run the preparation workflow with each update!

Latest Changes

[11.1.0] - 2026-07

Removed

  • All references to the private build of BCFtools. the --greedy behaviour is now released as standard in BCFtools 1.24

Added

  • STR functionality! This is currently specific to STRipy data, with a script to translate STRipy JSON data into a pseudo-joint called VCF
  • If there is appetite for STR functionality, this could be expanded to other STR callers.

Full changelog

Where to next

  • Getting Started Install the requirements, download annotation resources, and run your first cohort.

  • Features Logic modules, reanalysis mode, phenotype matching, and what Talos is (and isn't) for.

  • Configuration Full reference for the Talos TOML config and Nextflow parameters.

  • Changelog Release history and version-by-version changes.

When to use Talos

Talos is best suited for scenarios where:

  • You are performing routine reanalysis of undiagnosed individuals (e.g. monthly or quarterly).
  • You want to detect variants that have become reportable due to updates in gene–disease or variant–disease knowledge.
  • You aim to minimise the number of variants requiring manual review, optimising for specificity over sensitivity.
  • You are working with exome or genome sequencing data from previously analysed research or clinical cohorts.
  • You need a scalable, reproducible pipeline for family-based or cohort-scale analysis.

Talos is not currently designed for:

  • Identifying novel candidate disease genes or gene discovery.
  • Analysing short tandem repeats (STRs), mosaic variants, or variants outside standard clinical reporting regions.

Support for some of these variant types may be added in future releases.

Citation

If you use Talos in your research or clinical workflow, please cite:

Welland MJ, Ahlquist KD, De Fazio P, et al. Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts. medRxiv 2025.05.19.25327921; https://doi.org/10.1101/2025.05.19.25327921

@article{welland2025talos,
  title     = {Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts},
  author    = {Welland, Matthew J and Ahlquist, KD and De Fazio, Paul and Austin-Tse, Christina and Pais, Lynn and Wedd, Laura and Bryen, Samantha and Rius, Rocio and Franklin, Michael and Hall, Giles and et al.},
  journal   = {medRxiv},
  year      = {2025},
  doi       = {10.1101/2025.05.19.25327921},
  url       = {https://www.medrxiv.org/content/10.1101/2025.05.19.25327921},
}