Integral Assessment of the Epidemiological Risk of Genetic Lineages of Mycobacterium tuberculosis within the Genomic Epidemiological Surveillance System

Introduction. The spread of drug-resistant tuberculosis necessitates the implementation of novel analytical approaches for assessing epidemiological risks using wholegenome sequencing (WGS) data. Objective. To develop an Integrated Epidemiological Risk Index (IERI) that accounts for regional patterns of strain distribution as well as biological and genetic characteristics of Mycobacterium tuberculosis (MTB) associated with the development of drug resistance. Materials and Methods. The study included 5538 MTB genomes representing a wide range of genotypes from countries of the post-Soviet region. For each strain; the mutational burden in resistance-associated genes and the relative frequency of the genotype in the population were calculated. Logarithmic transformation; normalization; and aggregation methods were applied to construct a unified Integrated Epidemiological Risk Index (IERI). The predictive value of the index was evaluated using ROC analysis. Results. This study presents an Integrated Epidemiological Risk Index (IERI) that simultaneously incorporates the population prevalence of MTB genotypes and their mutational burden in genes associated with resistance to anti-tuberculosis drugs. ROC analysis confirmed the high predictive value of the IERI (AUC = 0.867) and the robustness of the method when applied to heterogeneous population datasets. Conclusion. The findings demonstrate the practical utility of the IERI for early identification of high-risk strains in the context of genomic epidemiological surveillance.