Feature Weighted Models (FWM) to address lineage dependency in drug-resistance prediction from Mycobacterium tuberculosis genome sequences.

Publication date: Jul 10, 2023

Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC), which has a strain- or lineage-based clonal population structure. The evolution of drug-resistance in the MTBC poses a threat to successful treatment and eradication of TB. Machine learning approaches are being increasingly adopted to predict drug-resistance and characterise underlying mutations from whole genome sequences. However, such approaches may not generalise well in clinical practice due to confounding from the population structure of the MTBC. To investigate how population structure affects machine learning prediction, we compared three different approaches to reduce lineage dependency in random forest (RF) models, including stratification, feature selection and feature weighted models. All RF models achieved moderate-high performance (AUC-ROC range: 0. 60-0. 98). First-line drugs had higher performance than second-line drugs, but it varied depending on the lineages in the training dataset. Lineage-specific models generally had higher sensitivity than global models which may be underpinned by strain-specific drug-resistance mutations or sampling effects. The application of feature weights and feature selection approaches reduced lineage dependency in the model and had comparable performance to unweighted RF models. https://github. com/NinaMercedes/RF_lineages. Supplementary data are available at Bioinformatics online.

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Concepts Keywords
Drugs Dependency
Genome Drug
High Genome
Mycobacterium Learning
Tuberculosis Lineage


Type Source Name
disease MESH Tuberculosis
pathway KEGG Tuberculosis
drug DRUGBANK Saquinavir
drug DRUGBANK Coenzyme M
drug DRUGBANK Rifampicin
drug DRUGBANK Isoniazid
drug DRUGBANK Ethambutol
drug DRUGBANK Pyrazinamide
drug DRUGBANK Ofloxacin
drug DRUGBANK Moxifloxacin
drug DRUGBANK Levofloxacin
drug DRUGBANK Amikacin
drug DRUGBANK Azelaic acid
drug DRUGBANK Capreomycin
drug DRUGBANK Kanamycin
drug DRUGBANK Streptomycin
drug DRUGBANK Cycloserine
drug DRUGBANK L-Cysteine
drug DRUGBANK Ethionamide
drug DRUGBANK Aminosalicylic Acid
drug DRUGBANK Flunarizine
drug DRUGBANK Pidolic Acid
drug DRUGBANK Dihydrostreptomycin
drug DRUGBANK Methylergometrine
drug DRUGBANK Aspartame

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