sage v4.0-rc.1

BQR

• Round consensus BQ to canonical quals and 1
• Increase min mapping quality for BQR from 10 to 50, and change AD/AF site thresholds
• Handle contexts with 0 identified errors
• BQR by consensus type
• Update error rate calculation to be robust to different qual distributions per-base

Read context & evidence counting

• New read context algorithm
• Changes to read context annotation
• New read counting conventions
• Approximate ref matching logic for long inserts
• Allow SNV/MNV support in soft-clips
• Fragment sync prefers aligned over non-aligned base quals

Qual model

• Qual filter dynamically scales with depth and splits map and base qual tests
• Explicit germline mode which incorporates empirical VAF implausibility into model
• Novel indel qual is conditionally boosted
• Changes to high depth mode
• Modify edge penalty more in line with realised error rates, and facilitates partial core qual contribution
• Use min base qual rather than mean base qual for MNVs
• Indel qual for MSI repeats is based on microsatellite empirical qual
• Jitter penalty model is overhauled

Filtering

• MED based on distance to soft clip instead of distance to end of read
• MED uses max per-read edge distance for fragments with overlap
• MED uses max edge distance across depth-supporting reads, not just ref
• MAX_READ_EDGE_DISTANCE_PERC split between panel and non-panel regions
• Fix dedupMnv bug
• Filter if ALT average fragment length << REF average fragment length
• Filter if portion of realigned read support for short indel is unusually high
• Filter at candidate phase if only one distinct fragment provides support
• Min fragment coordinate check is stepped and applies all the time
• Tumor VAF filter now uses recalibrated qual

Config:

• msi jitter files mandatory unless 'skip_msi_jitter' specified. Uses BAM path if 'jitter_param_dir' isn't specified