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Updated joint calling FAQ
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d-cameron authored Mar 4, 2021
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Expand Up @@ -167,14 +167,15 @@ Just specify multiple BAMs on the command line. GRIDSS will perform joint callin

### Should I do joint calling or run each sample individually?

Joint calling of related samples is strongly recommended for the following reasons:
**Joint calling should always be used for related samples** (e.g. tumour/normal or trio calling).
Joint calling will ensure that a common variant near the single-sample threshold of detection will be reliably reported as a shared variant.
This is not the case if the calling were done individually.
Note that this particular behaviour is not specific to GRIDSS and is common to all variant callers (hence the joint calling support in many callers).

- GRIDSS performs joint assembly across all samples.
Joint calling has higher coverage of shared variants thus resulting in more reliable assembly of that variant.
Furthmore joint calling allows for sensivity detection of variants that are present subclonally (or at low coverage) that would not be detected if called individually.
**Joint calling should always be used for related samples** (e.g. tumour/normal or trio calling). Joint calling will ensure that a common variant near the single-sample threshold of detection will be reliably reported as a shared variant. This is not the case if the calling were done individually. Note that this particular behaviour is not specific to GRIDSS and is common to all variant callers (hence the joint calling support in many callers).
Joint calling allows for sensivity detection of variants that are present subclonally (or at low coverage) that would not be detected if called individually.

GRIDSS performs joint assembly then reports a per-sample breakdown. Joint calling has higher coverage of shared variants thus resulting in more reliable assembly of that variant.

- GRIDSS performs joint variant calling across all samples.
Determining whether two SV calls in two different VCFs are actually the same call is non-trivial.
Imprecise calls are especially problematic since the coordinates may differ between the VCF, or a call may be precise in one VCF and not in the other.
A good example of why reconciling SV calls is so problematic is the case where call A (chrX:1-99->chrY:1-99) overlaps call B (chrX:50-149->chrY:1-99), call B overlaps call C (chrX:100-199->chrY:1-99), but A does not overlap C at all. Joint calling obviates this step.
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