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iCall: a genotype-calling algorithm for rare, low-frequency and common variants on the Illumina exome array
Jin Zhou1, Erwin Tantoso1, Lai-Ping Wong1
1Department of Statistics and Applied Probability, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Genome Institute of Singapore, Singapore, NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore and Life Sciences Institute, National University of Singapore, Singapore.
A new genotype calling algorithm, iCall, accurately identifies rare and low-frequency variants from next-generation genotyping arrays. iCall outperforms existing methods in call rates and concordance, particularly for minor alleles.
Area of Science:
- Genetics
- Bioinformatics
- Genomic Data Analysis
Background:
- Next-generation genotyping microarrays incorporate variants from large-scale sequencing projects.
- Accurate genotype calling for low-frequency and rare variants remains a challenge due to low allele support.
- Existing algorithms often fail to reliably call variants with low allele frequencies.
Purpose of the Study:
- Introduce iCall, a novel genotype calling algorithm designed for variants across all allele frequencies.
- Improve the accuracy and call rates for low-frequency and rare variants in genotyping data.
- Provide a robust tool for analyzing diverse genetic variants.
Main Methods:
- Developed iCall, a C++ based genotype calling algorithm for Linux systems.
- Benchmarked iCall against established algorithms: GenCall, optiCall, illuminus, and GenoSNP.
- Utilized hybridization intensity data from 12,370 individuals genotyped on the Illumina HumanExome BeadChip, with whole-genome sequencing data for validation.
Main Results:
- iCall demonstrated superior performance compared to single-stage calling algorithms in call rates and concordance.
- iCall significantly improved the accuracy of calling minor alleles, crucial for rare and low-frequency variants.
- Post-processing iCall output with zCall offered marginal performance gains over zCall combined with GenCall.
Conclusions:
- iCall provides a significant advancement in genotype calling accuracy, especially for rare and low-frequency variants.
- The algorithm offers improved reliability for analyzing comprehensive genetic variation from genotyping arrays.
- iCall represents a valuable tool for genomic studies requiring precise variant identification across the allele frequency spectrum.
