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jodyphelan / tbdb

Standard database for the TBProfiler tool
GNU Lesser General Public License v3.0
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Question regarding mutations #42

Closed bajwamoneeb closed 2 years ago

bajwamoneeb commented 2 years ago

Hi Jody,

Do you have all the WHO catalogue mutations in your database? I could not find whether you had the inhA_g-154a (fabG1_L203L) mutation. Also do you have Ser65Ser for PZA? I appreciate your help.

jodyphelan commented 2 years ago

Hi @bajwamoneeb

Yes, the WHO mutations should be in the database.

bajwamoneeb commented 2 years ago

Thanks! For the second question it is regarding the pncA gene. This mutation comes from CDC's TB survey of last year. They mention this mutation is not expected to confer resistance, but in their survey, 25/60 (42%) of labs reported resistance when using MGIT to grow this isolate. (0/1 reported resistance with VersaTREK).

jodyphelan commented 2 years ago

Thanks, for the info. This mutation is synonymous and looks like it is a phylogenetic lineage3 mutations (https://tbdr.lshtm.ac.uk/variants/pncA/c.195G>A). The tbdb list only contains mutations that actually cause resistance, so with the current criteria it does not qualify for inclusion. If this was included, it would lead to nearly all lineage3 isolates being classified as PZA resistant, so this is probably not a good idea.

bajwamoneeb commented 2 years ago

Hi Jody,

There is also the Leu203Leu fabg1 mutation which is associated with resistance in CDC's 2021 TB survey. Is this included in your list? See CDC's findings here: https://www.cdc.gov/tb/topic/laboratory/mpep/2020/sep-mpepIsolate.htm

jodyphelan commented 2 years ago

Hi @bajwamoneeb

Yes the Leu203Leu mutation in fabG1 is included. It's resistance conferring effect is not due to the synonymous change but it created an alternative promoter for the inhA gene and is listed as such in the database: inhA c.-154G>A (https://github.com/jodyphelan/tbdb/blob/master/tbdb.csv#L749-L750). See https://pubmed.ncbi.nlm.nih.gov/24354762/ for the original description.

bajwamoneeb commented 2 years ago

Ok that's interesting because for the sample that the CDC sent us we couldn't find that mutation with TB-Profiler, but when we sent the FASTQ's to Wadsworth to run in their pipeline they found that mutation.

jodyphelan commented 2 years ago

Are you using the latest version of tb-profiler and the database? For example here I've attached the report for the run SRR5067647 from the SRA. Maybe you could run this sample through your version and see if you get the same result? SRR5067647.results.txt

bajwamoneeb commented 2 years ago

So I'm using the docker tags available on quay for dealing with updates within the workflow I created. This should update the database as well correct?

jodyphelan commented 2 years ago

Yeah, if you use 4.2.0--pypyh5e36f6f_0 this should be the latest version

bajwamoneeb commented 2 years ago

Ah ok there was an issue in my WDL script which caused it to run TB-Profiler without updating via the latest docker tag version. I fixed it and I do see that mutation now.

jodyphelan commented 2 years ago

Ah that is good to hear!

bajwamoneeb commented 1 year ago

Also, can you output coverage for this gene in your report at least?

From: Moneeb Bajwa @.> Sent: Thursday, July 14, 2022 12:59 PM To: Jody Phelan @.>; jodyphelan/tbdb @.>; jodyphelan/tbdb @.> Cc: Mention @.***> Subject: Re: [jodyphelan/tbdb] Question regarding mutations (Issue #42)

Hi Jody,

I noticed actually that the sample associated with this question was classified as a lineage 4.1.1.1. The quality was decent as well.

From: Jody Phelan @.> Sent: Tuesday, June 14, 2022 9:34 AM To: jodyphelan/tbdb @.> Cc: Moneeb Bajwa @.>; Mention @.> Subject: Re: [jodyphelan/tbdb] Question regarding mutations (Issue #42)

Thanks, for the info. This mutation is synonymous and looks like it is a phylogenetic lineage3 mutations (https://tbdr.lshtm.ac.uk/variants/pncA/c.195G>Ahttps://nam12.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftbdr.lshtm.ac.uk%2Fvariants%2FpncA%2Fc.195G%253EA&data=05%7C01%7Cbajwa.m%40northeastern.edu%7C59c749cc58464b66195608da4e0aacc0%7Ca8eec281aaa34daeac9b9a398b9215e7%7C0%7C0%7C637908105004480616%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=8xDG5wG6CztNketNmMUbONJ5RUSi1hXdd0sT9%2B6u6W0%3D&reserved=0). The tbdb list only contains mutations that actually cause resistance, so with the current criteria it does not qualify for inclusion. If this was included, it would lead to nearly all lineage3 isolates being classified as PZA resistant, so this is probably not a good idea.

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