add mutations from issue #15

[jodyphelan]

Some new mutations

[jodyphelan]

After looking at these mutations here are my thoughts:

Drug	Gene	Mutation	Tree	Comment	Recommendation
isoniazid	Rv1908c	p.Arg632Cys	Rare with little validation work but not a phylogenetic mutation	Include
ethionamide	Rv3854c	p.Ser266Arg		Looks like phylogenetic mutation	Exclude
kanamycin	Rv2416c	c.-6G>T	Only seen in combination with r.1401a>g. Possible low level resistance?	Include
isoniazid	Rv1908c	p.Trp351*	Rare with little validation work but very probably mechanism through loss of function	Include
kanamycin	Rv2416c	c.-15C>T	Can't find this mutation in the provided literature	Exclude
rifampicin	Rv0667	p.His445Leu	RRDR	Include
rifampicin	Rv0667	p.His445Tyr	RRDR	Include
rifampicin	Rv0667	p.Ser450Leu	RRDR	Include
isoniazid	Rv1908c	p.Asp329Ala	Rare with little validation work but not a phylogenetic mutation	Include
ethionamide	Rv3854c	p.Asn345Lys		Looks like phylogenetic mutation	Exclude
isoniazid	Rv1908c	p.Met420Thr	Rare with little validation work but not a phylogenetic mutation	Include

[camusnimmo]

After looking at these mutations here are my thoughts:

Drug Gene Mutation Tree Comment Recommendation isoniazid Rv1908c p.Arg632Cys Rare with little validation work but not a phylogenetic mutation Include Cannot find evidence for this elsewhere, but agree could include

ethionamide Rv3854c p.Ser266Arg Looks like phylogenetic mutation Exclude Agree

kanamycin Rv2416c c.-6G>T Only seen in combination with r.1401a>g. Possible low level resistance? Include If not found in any other samples, and only seen in combination with known high confidence resistance conferring mutations, that is not enough evidence to say it is resistance conferring itself and so I would exclude

isoniazid Rv1908c p.Trp351* Rare with little validation work but very probably mechanism through loss of function Include Agree

kanamycin Rv2416c c.-15C>T Can't find this mutation in the provided literature Exclude Found this in the paper but in a strain with MICs below critical concentration therefore susceptible. Exclude

rifampicin Rv0667 p.His445Leu RRDR Include rifampicin Rv0667 p.His445Tyr RRDR Include rifampicin Rv0667 p.Ser450Leu RRDR Include Include all - are they not in there already?

isoniazid Rv1908c p.Asp329Ala Rare with little validation work but not a phylogenetic mutation Include Does seem rare. Reported in this study, but only tested for low level resistance and did not do WGS - just fabG1 promoter and katG, therefore cannot excluded oxyR-ahpC mutations. Perhaps insufficient evidence on this basis?

ethionamide Rv3854c p.Asn345Lys Looks like phylogenetic mutation Exclude Agree

isoniazid Rv1908c p.Met420Thr Rare with little validation work but not a phylogenetic mutation Include As for Arg632Cys, not found elsewhere but could include

[jodyphelan]

Thanks @camusnimmo. I'll merge in the mutations we both voted to include.

[jodyphelan]

Just to add... the rpoB mutations are already in the library through a wildcard-like specification whereby any mutation in the RRDR confers resistance.