exSTRa

exSTRa detects short tandem repeat (STR) expansions from Illumina paired-end whole-genome (WGS) and whole-exome (WES) sequencing data and is implemented as an R package.

Key Features:

• Implementation: Implemented as an R package for analysis of Illumina paired-end NGS data.
• Sequencing support: Supports analysis of whole-genome sequencing (WGS) and whole-exome sequencing (WES) paired-end data.
• Detection of STR expansions: Tailored to identify disease-causing full-mutation STR expansions at known loci.
• Ensemble integration: Operates alongside ExpansionHunter and STRetch in an ensemble approach, with reported performance of 82% precision, 100% recall, and 90% F1-score on Burrows-Wheeler Aligner (BWA)-aligned genomes.
• Clinical validation: Used to screen families with suspected repeat expansion disorders and identified full mutations at loci including AR, ATXN1, ATXN8, DMPK, FXN, and HTT.

Scientific Applications:

• Diagnostic screening: Enables genome-wide sequencing as a first-tier screen for known disease-related STR expansions.
• Genetic counseling and management: Provides molecular evidence of STR expansions to inform clinical management and genetic counseling.

Methodology:

Performance was characterized and optimized via a comparative analysis of eight STR analysis methods and a machine learning decision tree classifier to select the best combination for full-mutation detection, and performance was evaluated on BWA-aligned genomes alongside ExpansionHunter and STRetch.