ExpansionHunter-dev

This modified version of ExpansionHunter introduces the following new features:

• supports gzip-compressed input catalogs, and provides a -z option to compress the output files
• --analysis-mode low-mem-streaming which is like streaming mode and outputs roughly the same genotypes, but uses less memory
• --start-with, --n-loci, and --sort-catalog-by options allow processing a fixed number of loci from the input catalog
• --locus for filtering the input catalog to specific LocusId(s)
• --region for filtering the input catalog to a specific genomic region
• changes the Flanks can contain at most 5 characters N but found x Ns error to a warning, allowing ExpansionHunter to run to completion without terminating on these errors
• allows direct access to remote BAM/CRAM or reference FASTA files in Google Cloud Storage or S3
  • for access to private buckets, set environment variable:
    export GCS_OAUTH_TOKEN=$(gcloud auth application-default print-access-token)
  • for access to requester-pays buckets, also set environment variable
    export GCS_REQUESTER_PAYS_PROJECT=<your gcloud project>
• --cache-mates option makes --analysis-mode seeking run 2x to 3x faster without changing the output
  • for large catalogs, it is better to use the new "low-mem-streaming" analysis mode. However, if you do want to split a larger variant catalog into multiple shards and then process them using "seeking" mode with --cache-mates, it's important to presort the catalog by normalized motif (the alphabetically-first cyclic shift of a motif - ie. AGC rather than CAG). This ensures that loci with the same motif will be processed in the same shard, increasing cache hit rates and therefore speed due to this optimization.

Thank you to @maarten-k for testing out early versions and introducing substantial optimizations to the build process.

Citation

If you use this modified version of ExpansionHunter, please cite:

Insights from a genome-wide truth set of tandem repeat variation
Ben Weisburd, Grace Tiao, Heidi L. Rehm
bioRxiv 2023.05.05.539588; doi: https://doi.org/10.1101/2023.05.05.539588

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Expansion Hunter: a tool for estimating repeat sizes

There are a number of regions in the human genome consisting of repetitions of short unit sequence (commonly a trimer). Such repeat regions can expand to a size much larger than the read length and thereby cause a disease. Fragile X Syndrome, ALS, and Huntington's Disease are well known examples.

Expansion Hunter aims to estimate sizes of such repeats by performing a targeted search through a BAM/CRAM file for reads that span, flank, and are fully contained in each repeat.

Linux and macOS operating systems are currently supported.

License

Expansion Hunter is provided under the terms and conditions of the Apache License Version 2.0. It relies on several third party packages provided under other open source licenses, please see COPYRIGHT.txt for additional details.

Documentation

Installation instructions, usage guide, and description of file formats are contained in the docs folder.

Companion tools and resources

• A genome-wide STR catalog containing polymorphic repeats with similar properties to known pathogenic and functional STRs
• REViewer, a tool for visualizing alignments of reads in regions containing tandem repeats

Method

The method is described in the following papers:

• Egor Dolzhenko, Joke van Vugt, Richard Shaw, Mitch Bekritsky, and others, Detection of long repeat expansions from PCR-free whole-genome sequence data, Genome Research 2017

• Egor Dolzhenko, Viraj Deshpande, Felix Schlesinger, Peter Krusche, Roman Petrovski, and others, ExpansionHunter: A sequence-graph based tool to analyze variation in short tandem repeat regions, Bioinformatics 2019