Open bajwamoneeb opened 4 months ago
Hi @bajwamoneeb
Can you let me know which version of the software and database you are using?
Hi Jody I used the version 5.0.1 TB Profiler and the default database that version uses. CDC responded and their response was the following:
MPEP 2023-J does contain the variant rpoB_p.Pro454Ser. As you have probably noted in the MPEP report, this sample was not reported as rif resistant by any phenotypic testing method.
Variants known to be associated with rif resistance have been identified in the RRDR (codons 426 – 452) and at codons 170 and 491. The CDC pipeline Varpipe 1.0.2 reports and provides an interpretation for rpoB variants in these regions only.
rpoB_p.Pro454Ser is listed in the WHO catalogue as having an unknown association with rif resistance (limited data, no solo observances). I am not familiar enough with TBProfiler to comment on the underlying evidence used to support their interpretation of this variant. I think that you might need to reach out to TB Profiler for clarification.
Thanks, would you be able to try the latest version on conda (v6.2.1) to see if that fixes the issue? I think that mutation was removed between versions.
The mutation still came up. CMPEPJ2_HM_RE.results.json
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sample | main_lineage | sub_lineage | spoligotype | drtype | target_median_depth | pct_reads_mapped | num_reads_mapped | num_dr_variants | num_other_variants | rifampicin | isoniazid | ethambutol | pyrazinamide | moxifloxacin | levofloxacin | bedaquiline | delamanid | pretomanid | linezolid | streptomycin | amikacin | kanamycin | capreomycin | clofazimine | ethionamide | para-aminosalicylic_acid | cycloserine -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- CMPEPJ2_HM_RE | lineage4 | lineage4.3.4.2.1 | - | RR-TB | 67 | 99.58 | 1400511 | 3 | 24 | rpoB p.Pro454Ser (1.00) | - | - | - | - | - | - | fbiC c.2565_*55delGGCCTAGCCCCGGCGACGATGCCGGGTCGCGGGATGCGGCCCGTTGAGGAGCGGGGCAATCT (0.48), fbiC c.2565_*55delGGCCTAGCCCCGGCGACGATGCCGGGTCGCGGGATGCGGCCCGTTGAGGAGCGGGGCAATCT (1.00) | fbiC c.2565_*55delGGCCTAGCCCCGGCGACGATGCCGGGTCGCGGGATGCGGCCCGTTGAGGAGCGGGGCAATCT (0.48), fbiC c.2565_*55delGGCCTAGCCCCGGCGACGATGCCGGGTCGCGGGATGCGGCCCGTTGAGGAGCGGGGCAATCT (1.00) | - | - | - | - | - | - | - | - | -
Hi Jody,
We were sequencing CDC's MPEP samples using their varpipe TB pipeline and for one of the samples their pipeline did not pick up Rifampin resistance of rpoB_p.Pro454Ser; CDC confirmed that they did not expect this mutation for that particular sample (or don't consider it a drug resistance conferring mutation? Still waiting to hear back from them..). Your TB-Profiler however did show this mutation. Any insight?