Variant calling of high coverage samples with a restricted memory

A computer-implemented method comprising:

• receiving, at a calling subsystem of a variant caller, sequencing data comprising a plurality of reads of a genome sequence, wherein the calling subsystem of the variant caller is configured to detect a callable region of the sequencing data when a depth of the plurality of reads is above a callable region depth threshold, and wherein the calling subsystem of the variant caller is configured to send at least a portion of the callable region to a genotyping subsystem of the variant caller for variant calling of the callable region;
• monitoring memory used by the calling subsystem of the variant caller;
• when the memory used by the calling subsystem of the variant caller exceeds a memory threshold of a total amount of memory allocated to the calling subsystem of the variant caller, splitting the callable region;
• and
• sending a split portion of the callable region to the genotyping subsystem of the variant caller for the variant calling based on the split portion.