Evidence map›Paper›PMID 34461978›Full record

ArticleGenome medicine2021

GenTB: A user-friendly genome-based predictor for tuberculosis resistance powered by machine learning.

Matthias I Gröschel, Martin Owens, Luca Freschi, Roger Vargas, Maximilian G Marin, Jody Phelan, Zamin Iqbal, Avika Dixit, Maha R Farhat

Abstract read
In one paragraph

Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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

  1. Open-access genomic drug resistance prediction tools forJournal of clinical microbiology · 2026
    Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Predicting Drug Resistance inDiagnostics (Basel, Switzerland) · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Pan-lineage Mycobacterium tuberculosis reference genome for enhanced molecular diagnosis.DNA research : an international journal for rapid publication of reports on genes and genomes · 2024
    Article
  18. Article
  19. Review
  20. Review
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

9 authors.

Matthias I GröschelDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-2509-3034
Martin OwensDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Luca FreschiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Roger VargasDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Maximilian G MarinDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Jody PhelanFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.
Zamin IqbalEuropean Bioinformatics Institute, Hinxton, Cambridge, CB10 ISD, UK.
Avika DixitDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Maha R FarhatDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. maha_farhat@hms.harvard.edu.

Funding

New Tools for the interpretation of Pathogen Genomic Data with a focus on Mycobacterium tuberculosisK01ES026835 · NIEHS · MASSACHUSETTS GENERAL HOSPITAL · PI FARHAT, MAHA · 2015 to 2019
$1.1M
NIEHS NIH HHS K01 ES026835NIH HHS K01 ES026835NIH HHS R01 AI55765
6 · The paper itself

Abstract

backgroundMultidrug-resistant Mycobacterium tuberculosis (Mtb) is a significant global public health threat. Genotypic resistance prediction from Mtb DNA sequences offers an alternative to laboratory-based drug-susceptibility testing. User-friendly and accurate resistance prediction tools are needed to enable public health and clinical practitioners to rapidly diagnose resistance and inform treatment regimens.

resultsWe present Translational Genomics platform for Tuberculosis (GenTB), a free and open web-based application to predict antibiotic resistance from next-generation sequence data. The user can choose between two potential predictors, a Random Forest (RF) classifier and a Wide and Deep Neural Network (WDNN) to predict phenotypic resistance to 13 and 10 anti-tuberculosis drugs, respectively. We benchmark GenTB's predictive performance along with leading TB resistance prediction tools (Mykrobe and TB-Profiler) using a ground truth dataset of 20,408 isolates with laboratory-based drug susceptibility data. All four tools reliably predicted resistance to first-line tuberculosis drugs but had varying performance for second-line drugs. The mean sensitivities for GenTB-RF and GenTB-WDNN across the nine shared drugs were 77.6% (95% CI 76.6-78.5%) and 75.4% (95% CI 74.5-76.4%), respectively, and marginally higher than the sensitivities of TB-Profiler at 74.4% (95% CI 73.4-75.3%) and Mykrobe at 71.9% (95% CI 70.9-72.9%). The higher sensitivities were at an expense of ≤ 1.5% lower specificity: Mykrobe 97.6% (95% CI 97.5-97.7%), TB-Profiler 96.9% (95% CI 96.7 to 97.0%), GenTB-WDNN 96.2% (95% CI 96.0 to 96.4%), and GenTB-RF 96.1% (95% CI 96.0 to 96.3%). Averaged across the four tools, genotypic resistance sensitivity was 11% and 9% lower for isoniazid and rifampicin respectively, on isolates sequenced at low depth (< 10× across 95% of the genome) emphasizing the need to quality control input sequence data before prediction. We discuss differences between tools in reporting results to the user including variants underlying the resistance calls and any novel or indeterminate variants

conclusionsGenTB is an easy-to-use online tool to rapidly and accurately predict resistance to anti-tuberculosis drugs. GenTB can be accessed online at https://gentb.hms.harvard.edu , and the source code is available at https://github.com/farhat-lab/gentb-site .

Indexed as

Drug Resistance, BacterialMachine LearningSoftwareAntitubercular AgentsComputational BiologyDatabases, GeneticGenome, BacterialGenomicsHumansMicrobial Sensitivity TestsReproducibility of ResultsROC CurveTuberculosis, Multidrug-ResistantWeb BrowserWorkflowAntitubercular AgentsDiagnosticsDrug resistanceDrug-susceptibility testingMachine learningMDR-TBTuberculosisWhole genome sequencingXDR-TB

Identifiers

PMID34461978
PMCPMC8407037

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.