REscan

REscan infers repeat expansion loci and structural variation from paired-end short-read sequencing data to identify novel repeat expansions implicated in neurological diseases.

Key Features:

• Paired-end analysis: Leverages paired-end read orientation and mapping patterns to identify candidate repeat expansion loci.
• Mapping quality assessment: Analyzes mapping quality and the presence of read pairs with inadequately mapped mates to detect anomalous signals at loci.
• REscan statistic: Calculates a statistic that quantifies the proportion of reads oriented toward a locus that lack adequately mapped mates, with high values indicating likely repeat expansions.
• Validation on ALS cohorts: Validated using genome sequence data from 259 amyotrophic lateral sclerosis (ALS) cases and shown to discriminate carriers from non-carriers of large repeat expansions such as C9orf72.
• SAMtools integration: Integrates with SAMtools for controlled input of alignment data.
• Region specification options: Supports three options for specifying regions for output.

Scientific Applications:

• Neurological disease genetics: Detection of repeat expansions relevant to neurological disorders for downstream biological investigation.
• Carrier discrimination: Identification and discrimination of carriers versus non-carriers of large repeat expansions such as those in C9orf72.

Methodology:

Analyzes paired-end short-read sequencing data to identify discrepancies in read pair orientations and mapping quality, computes the REscan statistic quantifying reads oriented toward a locus lacking adequately mapped mates, and uses SAMtools for data input control.