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}

Version 3.1.2

Summary of changes:

• Add --write-nocalls-in-vcf option to write no-call sites in the VCF

Version 3.1.1

Summary of changes:
Minor update. Fix program error in low-depth or no-data regions. Completes analysis even when the input is a small bamlet (result is still a no-call).

Version 3.1.0

Summary of changes:

• Improve PMS2/PMS2CL differentiation
• Output protein changes at five potentially pathogenic sites in OPN1LW/OPN1MW
• Update region definitions for some families
• Add a few regions for fusion calling
  • CYP2D6, GBA, CYP11B1, the CFH gene cluster
• Improve VCFs. See documentation here
  • For each region, all gene copies are now in a single VCF file per sample, reported as sample columns in the VCF.
  • Report boundary coordinates and the truncated status of a haplotype in the VCF.
  • Report groups of haplotypes on the same chromosome when this information is available.

Version 3.0.0

Summary of changes:

• Added HBA1/HBA2 and OPN1LW/OPN1MW callers
• Added ~150 segmental duplication regions for GRCh38
• Improved gene callers
  • F8: Improved calling of Intron22 inversion and Exon1-22 deletion
  • NCF1: Improved assignment of genes to NCF1 vs. pseudogenes
  • PMS2: Improved assignment of genes to PMS2 vs. pseudogene. Updated the coordinates of the region to phase
  • IKBKG: Improved assignment of genes to IKBKG vs. pseudogene. Updated the coordinates of the region to phase
  • RCCX: Better calling of a multi-allelic site IVS2-13A/C>G
  • CFC1: Updated the coordinates of the region to phase
• For SMN1/STRC/PMS2/IKBKG/NCF1, variants are now called against the gene for gene haplotypes and against the paralog/pseudogene for paralog/pseudogene haplotypes
• Report F8 Intron 22 inversion and Exon1-22 deletion, and IKBKG 11.7kb deletion in VCFs
• Improved homopolymer/simple repeat masking before phasing
• Included filtered calls in VCFs
• Added GRCh37/hg19 support for 11 medically relevant gene families

Version 2.2.3

• Speeds up single sample analysis through multiprocessing by genomic region (-t is enabled)
• Adds program version and command to BAM and VCF headers
• Fixed a bug that may lead to failed analysis in low coverage samples
• Fixed a bug in F8 analysis

Version 2.2.2

• Fix low depth error so that even if one region fails depth check, the other regions will still produce results.
• Show version

Version 2.2.1

This version includes some light updates to Paraphase

• Simplify config files
• Prevent non-zero exit code
• Minor algorithm improvements

Please note that a new input file is required - the reference genome fasta file (specify with -r)

Version 2.1.0

This release includes some improvements to phasing and variant calling.

• Filter out spurious variants before phasing
• Filter out spurious haplotypes after phasing
• Better handle homozygous cases

Version 2.0.0

This release extends Paraphase to resolve highly homologous genes listed below

• SMN1/SMN2 (spinal muscular atrophy)
• RCCX module
  • CYP21A2 (21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia)
  • TNXB (Ehlers-Danlos syndrome)
  • C4A/C4B (relevant in autoimmune diseases)
• PMS2 (Lynch Syndrome)
• STRC (hereditary hearing loss and deafness)
• IKBKG (Incontinentia Pigmenti)
• NCF1 (chronic granulomatous disease; Williams syndrome)
• NEB (Nemaline myopathy)
• F8 (intron 22 inversion, Hemophilia A)
• CFC1 (heterotaxy syndrome)