Assigned labels and filters

CNV labels

CNV calls in the vcf files are annotated with potential FILTER values, that describe a specific reason a call may not be trustworthy.

Filter name	Description
min_size	CNV call below minimum size (<1000bp)
min_probes	CNV call from <5 probes
min_density	CNV call with <10 probes/Mb
high_probe_dens	Probe density of segment is higher than 99% of the array
probe_gap	Probe coverage of segment has considerable gap (min. 33% depending on probe number - see config)

All CNV calls are given a label based on their check score, filters and reference match.

The labels described here are always available, but can be changed or new labels can be added through the config file
If not other category fits (which should not occur with default settings), then the last defined “Exclude call” label will always be assigned.

CNV label	Minimum Check_Score	FILTER values not allowed	Match in Reference Sample	Description
Critical de-novo	≥55	high_probe_dens, probe_gap, min_size, min_probes, min_density	No	High-confidence CNV call with likely biological relevance
Reportable de-novo	≥55	min_size, min_probes, min_density	No	CNV call with potential biological relevance
de-novo call	≥ 0	min_size, min_probes, min_density	No	General CNV call meeting minimal quality requirements
Reference genotype	≥ 0 (any)		Yes	CNV call that matches the reference sample genotype
Excluded call	≥ 0 (any)		No	CNV call that does not match minimal quality requirements (close to “noise”)

Each SNV is first assigned to a category based on annotation and overlap with hPSC hotspots or sample specific ROIs>

SNV_category	Description
hotspot-match	SNV matching a known stem cell hotspot mutation (see also SNV hotspot coverage)
hotspot-gene	SNV overlapping a sample specific regions of interest
protein-ablation	SNV (likely) fully disrupting protein function (i.e. frameshift, stop gain, stop loss)
protein-changing	SNV causing a change the protein sequence (i.e. missense, inframe)
other	SNV with other unclear or undetermined effect on protein function

SNVs are then assigned a label based on their category, reference match and genotype quality:

SNV Label	Categories	Match in Reference Sample	Genotype quality
Critical	hotspot-match	No	high
Reportable	ROI-overlap, hotspot-gene, protein-ablation	No	high
Unreliable critical/reportable	hotspot-match, ROI-overlap, hotspot-gene, protein-ablation	No	low
de-Novo	protein-changing, other	No	any
Reference genotype	any	Yes	any