The HaplotypeCaller is a more recent and sophisticated tool than the UnifiedGenotyper. Its ability to call SNPs is equivalent to that of the UnifiedGenotyper, and its ability to call indels is far superior. We recommend using HaplotypeCaller in all cases, with only a few exceptions:
- If you want to analyze more than 100 samples at a time (for performance reasons)
- If you are working with non-diploid organisms (UG can handle different levels of ploidy while HC cannot)
- If you are working with pooled samples (also due to the HC’s limitation regarding ploidy)
In those cases, we recommend using UnifiedGenotyper instead of HaplotypeCaller.