Data · dataset · 2015
Whole genome sequences for M.tuberculosis isolates from the TDR strain bank
Listed in LSHTM Data Compass
Combating the spread of drug resistant tuberculosis is a global health priority.
Description
Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance.
To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs.
Read the rest (2 more)
In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability.
Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites.
Links
Where it is published
- LSHTM Data Compass record datacompass.lshtm.ac.uk/id/eprint/193/1/AdditionalFile1-TableS1.docx ↗
landing page · from lshtm ac uk
Catalogue records · 1
- OAI-PMH record datacompass.lshtm.ac.uk/cgi/oai2?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3… ↗
metadata API · from lshtm ac uk
Topics
- From keywords
- Earth & Environmental Science · Humanities · Life Sciences · Medicine & Health · Social Science
- Inferred from text
- Genetics 70%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| LSHTM Data Compass | oai:datacompass.lshtm.ac.uk:193 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].anzsrc:group:3105 | enrichment · lshtm ac uk | taxonomy-embedding@1.0.0 | title+keywords+description (70%) |
| concepts[field].local:field:earth-environmental | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:humanities | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:medicine-health | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:social-science | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| description | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | /metadata/dc/description |
| license | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | /metadata/dc/rights |
| publication_date | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| title | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | /metadata/dc/title |