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Updated: Sep 12, 2025

Infinium Assay for Large-scale SNP Genotyping Applications
Published on: November 19, 2013
Genotyping TOMM40'523 poly-T polymorphisms using whole-genome sequencing
Ricardo A Vialle1, Lei Yu2, Yan Li2
1Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 West Harrison Street, Chicago, IL 60612, USA; Graduate Program in Bioinformatics, Professional and Technical Education Sector (SEPT), Universidade Federal do Paraná (UFPR), R. Dr. Alcides Vieira Arcoverde 1225, Curitiba, Paraná 81520-260, Brazil.
None:
The TOMM40'523 poly-T repeat polymorphism (rs10524523) has been associated with cognitive decline and Alzheimer's disease (AD) progression. Challenges in processing whole-genome sequencing (WGS) data traditionally require additional PCR and targeted sequencing assays to genotype these polymorphisms. We introduce a computational pipeline that integrates multiple short tandem repeat (STR) detection tools in an ensemble machine learning model using XGBoost. Using a sample of 1,202 participants from 4 cohort studies, we benchmarked our method against PCR-based measures. Our ensemble model outperformed individual STR tools, improving repeat length estimation accuracy (R2 = 0.92) and achieving an accuracy rate of 93.2% compared with PCR-derived genotypes. Additionally, we validated our WGS-derived genotypes by replicating previously reported associations between TOMM40'523 variants and cognitive decline. Our computational genotyping tool is a scalable and reliable alternative to PCR-based assays, enabling broader investigations of TOMM40 variation in studies with WGS data.
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