Add some common resistance-conferring mutations that do no exist in population graph

[mbhall88]

See https://github.com/mbhall88/drprg-paper/issues/2 and https://github.com/mbhall88/drprg-paper/issues/2 for the motivation.

There are some common mutations which do not exist in the reference graph. As such, when there is a minor allele in a sample for one of these mutations, we do not detect it. This is because discover only finds major alleles, and to detect minor alleles, the allele must exist in the graph in the first place.

[mbhall88]

This seems to have worked reasonably well

Tool	Drug	ΔFN	ΔFP
drprg	Amikacin	0	0
drprg	Capreomycin	0	-1
drprg	Delamanid	0	5
drprg	Ethambutol	-1	4
drprg	Ethionamide	-52	22
drprg	Isoniazid	0	0
drprg	Kanamycin	0	0
drprg	Levofloxacin	0	0
drprg	Linezolid	-1	0
drprg	Moxifloxacin	0	-1
drprg	Ofloxacin	0	0
drprg	Pyrazinamide	-2	-1
drprg	Rifampicin	-5	0
drprg	Streptomycin	0	0

Quite a few ETO FPs though, which I will take a look at before moving on

[mbhall88]

So all of those "new" ETO FPs are strong calls for a mutation I recently added (fabG1 L203L) which mykrobe and tb-profiler also call.

[iqbal-lab]

This sounds great!

[mbhall88]

The delamanid FPs are caused by us calling minor alleles for ddn L49P. One of these is backed up by the other callers, one seems like a decent minor call, but not made by the other callers, and the rest are very low depth. This has made me realise I am not applying the same variant filters to the minor allele calls as I do the normal major allele calls. For instance, some of these delamanid minor calls only have depth 2x on the minor allele, so these should be filtered out

[iqbal-lab]

So, stepping back, what are the rules we want to apply to call a minor? Above x% of the total reads at that variant (either allele) and above some min absolute number, right? I'd think no other filters?

[mbhall88]

The extra EMB FPs are also the same reasons as the delamanid ones.

I think we can just use the same filters for minors as we do for majors.

• Min. depth 3x
• At least one read on each strand
• Min. GT CONF 5 (which doesn't really apply to minor alleles I guess so we could bin this or just leave it in as it seems unlikely?)

We also have an FRS for majors, which we obviously don't want for minors

[iqbal-lab]

The model behind Gt conf is only meaningful for majors, so I'd bin it for minors

[mbhall88]

Adding in the filtering of minors gives this diff to the results above

Tool	Drug	ΔFN	ΔFP
drprg	Amikacin	0	0
drprg	Capreomycin	0	0
drprg	Delamanid	0	-1
drprg	Ethambutol	0	-2
drprg	Ethionamide	0	0
drprg	Isoniazid	0	0
drprg	Kanamycin	0	0
drprg	Levofloxacin	0	-1
drprg	Linezolid	0	0
drprg	Moxifloxacin	0	-1
drprg	Ofloxacin	0	0
drprg	Pyrazinamide	0	0
drprg	Rifampicin	0	-1
drprg	Streptomycin	1	0

---

So the diff for this overarching issue is

Tool	Drug	ΔFN	ΔFP
drprg	Amikacin	0	0
drprg	Capreomycin	0	-1
drprg	Delamanid	0	4
drprg	Ethambutol	-1	2
drprg	Ethionamide	-52	22
drprg	Isoniazid	0	0
drprg	Kanamycin	0	0
drprg	Levofloxacin	0	-1
drprg	Linezolid	-1	0
drprg	Moxifloxacin	0	-2
drprg	Ofloxacin	0	0
drprg	Pyrazinamide	-2	-1
drprg	Rifampicin	-5	-1
drprg	Streptomycin	1	0