zCall: a rare variant caller for array-based genotyping: genetics and population analysis

Abstract

Summary: zCall is a variant caller specifically designed for calling rare single-nucleotide polymorphisms from array-based technology. This caller is implemented as a post-processing step after a default calling algorithm has been applied. The algorithm uses the intensity profile of the common allele homozygote cluster to define the location of the other two genotype clusters. We demonstrate improved detection of rare alleles when applying zCall to samples that have both Illumina Infinium HumanExome BeadChip and exome sequencing data available.

Availability: http://atguweb.mgh.harvard.edu/apps/zcall.

Contact: bneale@broadinstitute.org

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1.

Example genotype intensity plot. Schematic of how zCall assigns genotypes to points based on the normalized intensity distribution of the homozygote clusters. In normalized intensity space, the common allele homozygote clusters lie along the x and y axes (circles and pluses) and the heterozygote cluster lies along the line y = x (circled pluses). The three genotype clusters can be separated by a vertical (x = t_X) and horizontal line (y = t_Y) that are derived by solving for the location of z standard deviations from the mean in the direction of the minor axis of the cluster. After t_X and t_Y have been defined, points are assigned genotypes based on their position relative to the thresholds. Points in Quadrant I are classified as homozygotes (BB), points in Quadrant II are classified as heterozygotes (AB), points in Quadrant III are classified as No Calls, and points in Quadrant IV are classified as homozygotes (AA)