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印度锡金邦结核分枝杆菌复合群的分子多样性及利用人工智能预测优势 spoligotypes。

Molecular diversity of Mycobacterium tuberculosis complex in Sikkim, India and prediction of dominant spoligotypes using artificial intelligence.

机构信息

N.E. Region, Indian Council of Medical Research (ICMR)-Regional Medical Research Centre, Post Box #105, Dibrugarh, Assam, 786 001, India.

National Tuberculosis Elimination Programme (NTEP), Gangtok, Sikkim, India.

出版信息

Sci Rep. 2021 Apr 1;11(1):7365. doi: 10.1038/s41598-021-86626-z.

DOI:10.1038/s41598-021-86626-z
PMID:33795751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8016865/
Abstract

In India, tuberculosis is an enormous public health problem. This study provides the first description of molecular diversity of the Mycobacterium tuberculosis complex (MTBC) from Sikkim, India. A total of 399 Acid Fast Bacilli sputum positive samples were cultured on Lőwenstein-Jensen media and genetic characterisation was done by spoligotyping and 24-loci MIRU-VNTR typing. Spoligotyping revealed the occurrence of 58 different spoligotypes. Beijing spoligotype was the most dominant type constituting 62.41% of the total isolates and was associated with Multiple Drug Resistance. Minimum Spanning tree analysis of 249 Beijing strains based on 24-loci MIRU-VNTR analysis identified 12 clonal complexes (Single Locus Variants). The principal component analysis was used to visualise possible grouping of MTBC isolates from Sikkim belonging to major spoligotypes using 24-MIRU VNTR profiles. Artificial intelligence-based machine learning (ML) methods such as Random Forests (RF), Support Vector Machines (SVM) and Artificial Neural Networks (ANN) were used to predict dominant spoligotypes of MTBC using MIRU-VNTR data. K-fold cross-validation and validation using unseen testing data set revealed high accuracy of ANN, RF, and SVM for predicting Beijing, CAS1_Delhi, and T1 Spoligotypes (93-99%). However, prediction using the external new validation data set revealed that the RF model was more accurate than SVM and ANN.

摘要

在印度,结核病是一个巨大的公共卫生问题。本研究首次描述了来自印度锡金邦的结核分枝杆菌复合群(MTBC)的分子多样性。共培养了 399 份抗酸杆菌痰阳性样本洛氏培养基,并通过 spoligotyping 和 24 个位点 MIRU-VNTR 分型进行遗传特征分析。 spoligotyping 显示发生了 58 种不同 spoligotype。北京 spoligotype 是最主要的类型,占总分离株的 62.41%,并与多药耐药性有关。基于 24 个位点 MIRU-VNTR 分析对 249 株北京菌株进行最小生成树分析,确定了 12 个克隆复合体(单一位点变体)。主成分分析用于使用 24-MIRU VNTR 谱可视化来自锡金的 MTBC 分离株主要 spoligotype 可能的分组。基于人工智能的机器学习(ML)方法,如随机森林(RF)、支持向量机(SVM)和人工神经网络(ANN),用于使用 MIRU-VNTR 数据预测 MTBC 的优势 spoligotype。K 折交叉验证和使用未见测试数据集的验证显示,ANN、RF 和 SVM 对预测北京、CAS1_Delhi 和 T1 spoligotype 的准确率很高(93-99%)。然而,使用外部新验证数据集进行预测表明,RF 模型比 SVM 和 ANN 更准确。

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