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KRLMM: an adaptive genotype calling method for common and low frequency variants.

Authors :
Ruijie Liu
Dai, Zhiyin
Yeager, Meredith
Irizarry, Rafael A.
Ritchie, Matthew E.
Source :
BMC Bioinformatics. 2014, Vol. 15 Issue 1, p1-22. 22p. 1 Diagram, 2 Charts, 8 Graphs.
Publication Year :
2014

Abstract

Background SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the underlying models rely on each genotype having a reasonable number of observations to ensure accurate clustering. Results Here we develop KRLMM, a new method for converting raw intensities into genotype calls that aims to overcome this issue. Our method is unique in that it applies careful between sample normalization and allows a variable number of clusters k (1, 2 or 3) for each SNP, where k is predicted using the available data. We compare our method to four genotyping algorithms (GenCall, GenoSNP, Illuminus and OptiCall) on several Illumina data sets that include samples from the HapMap project where the true genotypes are known in advance. All methods were found to have high overall accuracy (> 98%), with KRLMM consistently amongst the best. At low minor allele frequency, the KRLMM, OptiCall and GenoSNP algorithms were observed to be consistently more accurate than GenCall and Illuminus on our test data. Conclusions Methods that tailor their approach to calling low frequency variants by either varying the number of clusters (KRLMM) or using information from other SNPs (OptiCall and GenoSNP) offer improved accuracy over methods that do not (GenCall and Illuminus). The KRLMM algorithm is implemented in the open-source crlmm package distributed via the Bioconductor project (http://www.bioconductor. org). [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14712105
Volume :
15
Issue :
1
Database :
Academic Search Index
Journal :
BMC Bioinformatics
Publication Type :
Academic Journal
Accession number :
96369113
Full Text :
https://doi.org/10.1186/1471-2105-15-158