Evidence map›Paper›PMID 25970423›Full record

ArticlePloS one2015

Detection of Low-Level Mixed-Population Drug Resistance in Mycobacterium tuberculosis Using High Fidelity Amplicon Sequencing.

Rebecca E Colman, James M Schupp, Nathan D Hicks, David E Smith, Jordan L Buchhagen, Faramarz Valafar, Valeriu Crudu, Elena Romancenco, Ecaterina Noroc, Lynn Jackson and 5 more

Registry-linked trialAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04923958 (Rapid Research in Diagnostics Development for TB Network), which is not on this map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04923958 narecruitingnot on this mapstarted 2021, after this paper: background citation

Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) Study

TypeinterventionalSponsorUniversity of California, San FranciscoRan2021 to 2031Enrolled26,436ConditionsTuberculosisArmsNovel mycobacterial culture techniques, Novel sputum smear microscopy techniques, Sputum-based molecular assays, Tongue swab-based molecular assays, Urine LAM assays
3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
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  7. Article
  8. Article
  9. Xpert MTB/RIF Ultra-resistant and MTBDRAntimicrobial agents and chemotherapy · 2025
    Article
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  20. Molecular Capture ofInternational journal of molecular sciences · 2023
    Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Rebecca E ColmanTranslational Genomics Research Institute, Flagstaff, AZ, United States of America.
James M SchuppTranslational Genomics Research Institute, Flagstaff, AZ, United States of America.
Nathan D HicksTranslational Genomics Research Institute, Flagstaff, AZ, United States of America.
David E SmithTranslational Genomics Research Institute, Flagstaff, AZ, United States of America.
Jordan L BuchhagenTranslational Genomics Research Institute, Flagstaff, AZ, United States of America.
Faramarz ValafarSan Diego State University, San Diego, CA, United States of America.
Valeriu CruduPhthisiopneumology Institute (PPI), Chisinau, Republic of Moldova.
Elena RomancencoUniversity of California San Diego, San Diego, CA, United States of America.
Ecaterina NorocPhthisiopneumology Institute (PPI), Chisinau, Republic of Moldova.
Lynn JacksonUniversity of California San Diego, San Diego, CA, United States of America.
Donald G CatanzaroUniversity of Arkansas College of Education and Health Professions, Fayetteville, AR, United States of America.
Timothy C RodwellUniversity of California San Diego, San Diego, CA, United States of America.
Antonino CatanzaroUniversity of California San Diego, San Diego, CA, United States of America.
Paul KeimTranslational Genomics Research Institute, Flagstaff, AZ, United States of America; Center for Microbial Genetics & Genomics, Northern Arizona University, Flagstaff, AZ, United States of America.
David M EngelthalerTranslational Genomics Research Institute, Flagstaff, AZ, United States of America.

Funding

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Maile Ann Young Karris · 1994 to 2026
$78.4M
Rapid Tests for Drug Resistance to Detect Extensively Drug-Resistant TuberculosisU01AI082229 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CATANZARO, ANTONINO · 2009 to 2013
$10.9M
An Integrated Tabletop Platform for Rapid Detection of XDR-TB in Clinical SamplesR01AI111435 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RODWELL, TIMOTHY CHARLES · 2014 to 2018
$5.4M
Evolutionary and Functional Significance of Novel Mutations in MDR-XDR TBR01AI105185 · NIAID · SAN DIEGO STATE UNIVERSITY · PI VALAFAR, FARAMARZ · 2013 to 2021
$5.3M
NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI105185NIAID NIH HHS R01AI105185NIAID NIH HHS R01 AI111435NIAID NIH HHS U01 AI082229NIAID NIH HHS U01-AI082229
6 · The paper itself

Abstract

Undetected and untreated, low-levels of drug resistant (DR) subpopulations in clinical Mycobacterium tuberculosis (Mtb) infections may lead to development of DR-tuberculosis, potentially resulting in treatment failure. Current phenotypic DR susceptibility testing has a theoretical potential for 1% sensitivity, is not quantitative, and requires several weeks to complete. The use of "single molecule-overlapping reads" (SMOR) analysis with next generation DNA sequencing for determination of ultra-rare target alleles in complex mixtures provides increased sensitivity over standard DNA sequencing. Ligation free amplicon sequencing with SMOR analysis enables the detection of resistant allele subpopulations at ≥0.1% of the total Mtb population in near real-time analysis. We describe the method using standardized mixtures of DNA from resistant and susceptible Mtb isolates and the assay's performance for detecting ultra-rare DR subpopulations in DNA extracted directly from clinical sputum samples. SMOR analysis enables rapid near real-time detection and tracking of previously undetectable DR sub-populations in clinical samples allowing for the evaluation of the clinical relevance of low-level DR subpopulations. This will provide insights into interventions aimed at suppressing minor DR subpopulations before they become clinically significant.

Indexed as

Antitubercular AgentsDNA, BacterialDrug Resistance, Multiple, BacterialGene FrequencyGenetic LociHigh-Throughput Nucleotide SequencingHumansMicrobial Sensitivity TestsMolecular Diagnostic TechniquesMycobacterium tuberculosisPolymorphism, Single NucleotideSequence Analysis, DNASputumTuberculosis, Multidrug-ResistantTuberculosis, PulmonaryAntitubercular AgentsDNA, Bacterial

Identifiers

PMID25970423
PMCPMC4430321

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.