TB-DROP: deep learning-based drug resistance prediction of Mycobacterium tuberculosis utilizing whole genome mutations.

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Abstract

The most widely practiced strategy for constructing the deep learning (DL) prediction model for drug resistance of Mycobacterium tuberculosis (MTB) involves the adoption of ready-made and state-of-the-art architectures usually proposed for non-biological problems. However, the ultimate goal is to construct a customized model for predicting the drug resistance of MTB and eventually for the biological phenotypes based on genotypes. Here, we constructed a DL training framework to standardize and modularize each step during the training process using the latest tensorflow 2 API. A systematic and comprehensive evaluation of each module in the three currently representative models, including Convolutional Neural Network, Denoising Autoencoder, and Wide & Deep, which were adopted by CNNGWP, DeepAMR, and WDNN, respectively, was performed in this framework regarding module contributions in order to assemble a novel model with proper dedicated modules. Based on the whole-genome level mutations, a de novo learning method was developed to overcome the intrinsic limitations of previous models that rely on known drug resistance-associated loci. A customized DL model with the multilayer perceptron architecture was constructed and achieved a competitive performance (the mean sensitivity and specificity were 0.90 and 0.87, respectively) compared to previous ones. The new model developed was applied in an end-to-end user-friendly graphical tool named TB-DROP (TuBerculosis Drug Resistance Optimal Prediction: https://github.com/nottwy/TB-DROP ), in which users only provide sequencing data and TB-DROP will complete analysis within several minutes for one sample. Our study contributes to both a new strategy of model construction and clinical application of deep learning-based drug-resistance prediction methods.© 2024. The Author(s).