Version 3.2.0

Summary of changes:

1. Updates to better handle targeted data

• Filter reads on rq (>=0.99), if rq is present in input bam
• Add a --targeted option for targeted data to drop the assumption of uniform coverage across the genome
• Add two optional parameters for targeted data
  • --min-read-variant: Partially controls the number of supporting reads for a variant for identifying variants used for phasing. The cutoff for variant-supporting reads is determined by min(this number, max(5, depth*0.11)). Default is 20. At standard WGS depth, the default value is overwritten by max(5, depth*0.11).
    • Use cases: 1) Set this number low for low-coverage data or to increase sensitivity. 2) For targeted data with high coverage, set this number relatively high to avoid picking up sequencing errors and to reduce run time.
  • --min-read-haplotype: Minimum number of unique supporting reads for a haplotype. Default is 4. For targeted data with high coverage, this cutoff can be increased to reduce errors and to reduce run time.

2. Updates to target regions:

• Update coordinates of some target regions to include full genes whenever possible: pms2,ikbkg,hba,DDT,MBD3L2,DEFA1,PRY,CHRNA7,DHX40,GOLGA8A,IQCK,NXF2,OTOA,PDPK1,POTEI,RGPD1,RGPD3,RSPH10B,SIK1,TMLHE,CBS,KCNE1,CASTOR2,NBPF4,RGPD5,GOLGA8N,POTEB,ANKRD20A1,NSF
• Add TNXB as a region on its own so that the full gene can be genotyped (the RCCX region only includes part of TNXB)

3. Algorithmic changes

• Improve fusion calling in cases of homozygous deletion
• Add some homozygous sites to cover target regions evenly during phasing to improve read assignment to haplotypes and variant calling
• Update a few gene-specific callers
  • hba: Add calling of 4.2 deletion/duplication
  • smn1: If homozygous throughout region, default to CN =2 instead of 1; Drop carrier call if only one SMN1 haplotype is found but the total CN of SERF1A/B (neighboring locus) is larger than the total CN of SMN1/2
  • ikbkg: Improve calling of the 11.7kb deletion; Update the config to genotype the entire gene
  • ncf1: Drop carrier call if only one NCF1 haplotype is found but the total CN of GTF2I (neighboring locus) is larger than the total CN of NCF1 family
  • rccx: Better handle homozygous deletion cases
  • pms2: Update the config to genotype the entire gene

4. Other changes:

• Support cram as input
• Standardize haplotype naming across regions: {gene name}_{haplotype name}