Distribution of Beijing Genotype Among Clinical Isolates of M. tuberculosis Circulating in Kazakhstan

Introduction. Methods of genotyping of M. tuberculosis play an important role in tuber?ulosis (TB) infection control. These techniques are used to detect or exclude laboratory errors, control recurrent cases, and determine ways of TB transmission. Today, there are more than 10 methods of genotyping; MIRU-VNTR is one of the most widely used methods in the world. In this study we aimed to estimate biological diversity of clinical isolates of M. tuberculosis from different regions of Kazakhstan based on MIRU-VNTR analysis.Materials and methods. MIRU-VNTR was used to genotype 134 clinical isolates of M. tuberculosis isolated from new cases and recurrent cases of TB from different regions of Kazakhstan.  Amplification was done using 15 MIRU-VNTR loci. Determination of the number of tandem repeats in the corresponding locus was performed via Quantity One v.4.4.0 (BioRad, USA) software. H37Rv (NC_000962) reference strain was used as a positive control.Results. Phylogenic tree was built using www.miru-vntr.org web-resource based on the results of MIRU-VNTR analysis. Beijing family strains associated with drug resistance to antituberculosis drugs were prevalent among all isolates of M. tuberculosis circulating in Kazakhstan. Strains of the Beijing genotype were prevalent in both new cases (65%) and recurrent cases (89.4%) of tuberculosis. The second meaningful genotype that is spread in the territory of Kazakhstan is LAM, the frequency of distribution is 7.3% in new and 4.5% in recurrent cases. Other families of M. tuberculosis such as Ural, Haarlem, CAS, NEW-1, S were found in less than 4% of cases.Conclusion. Prevalence of Beijing family strains among all isolates of M. tuberculosis from different regions of Kazakhstan was shown. Strains of this family are prevalent among young people. This genotype is responsible for ongoing TB transmission in the present time. This genotype is more virulent; therefore, investigation of the epidemiology of the Beijing genotype plays crucial role in the monitoring of tuberculosis.

Whole genome sequencing of M.tuberculosis in Kazakhstan: preliminary data

Background: Tuberculosis is a major public health problem which infects one third of the world’s population, resulting in more than two million deaths every year. The emergence of whole genome sequencing (WGS) technologies as a primary research tool has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (MTB) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission, and treatment. To our knowledge, studies involving WGS of Kazakhstani strains of M. tuberculosis have not yet been performed. Aim: To perform whole genome sequencing of M. tuberculosis strains isolated in Kazakhstan and analyze sequence data (first experience and preliminary data). Results: In the present report, we announce the whole-genome sequences of the two clinical isolates of Mycobacterium tuberculosis, MTB-489 and MTB-476, isolated from the Almaty region. These strains were part of a repository that was created during our project “Creating prerequisites of personalized approach in the diagnosis and treatment of tuberculosis, based on whole genome-sequencing of M. tuberculosis”. Two strains were isolated from sputum samples of patients P1 and P2. Phenotypically, two isolates were drug-susceptible M. tuberculosis. Sequence data was compared with the publicly available data on M. tuberculosis laboratory strain H37Rv and others. The sequencing of the strains was performed on a Roche 454 GS FLX+ next-generation sequencing platform using a standard protocol for a shotgun genome library. The whole genome sequencing was performed for two M.tuberculosis isolates MTB-476 and MTB-489. 96 M bp with an average read length of 520 bp, approximately 21.8X coverage and 104.2 M bp with an average read length of 589 bp and approximately 23.7X coverage were generated for the MTB-476 and MTB-489, respectively. The genome of MTB-476 consists of 257 contigs, 4204 CDS, 46 tRNAs and 3 rRNAs. MTB-489 has 187 contigs, 4183 CDS, 45 tRNAs and 3rRNAs. Conclusion: The results of genome assembling have been submitted into NCBI GenBank and are available for public access under the accession numbers AZBA00000000 and AZAZ00000000. These genome assemblies can be useful for comparative genome analysis and for identification of novel SNPs and gene variants in genomes of M.tuberculosis

Whole genome sequencing of M.tuberculosis in Kazakhstan: preliminary data

Background: Tuberculosis is a major public health problem which infects one third of the world’s population, resulting in more than two million deaths every year. The emergence of whole genome sequencing (WGS) technologies as a primary research tool has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (MTB) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission, and treatment. To our knowledge, studies involving WGS of Kazakhstani strains of M. tuberculosis have not yet been performed.Aim: To perform whole genome sequencing of M. tuberculosis strains isolated in Kazakhstan and analyze sequence data (first experience and preliminary data).Results: In the present report, we announce the whole-genome sequences of the two clinical isolates of Mycobacterium tuberculosis, MTB-489 and MTB-476, isolated from the Almaty region. These strains were part of a repository that was created during our project “Creating prerequisites of personalized approach in the diagnosis and treatment of tuberculosis, based on whole genome-sequencing of M. tuberculosis”. Two strains were isolated from sputum samples of patients P1 and P2. Phenotypically, two isolates were drug-susceptible M. tuberculosis. Sequence data was compared with the publicly available data on M. tuberculosis laboratory strain H37Rv and others. The sequencing of the strains was performed on a Roche 454 GS FLX+ next-generation sequencing platform using a standard protocol for a shotgun genome library. The whole genome sequencing was performed for two M.tuberculosis isolates MTB-476 and MTB-489. 96 M bp with an average read length of 520 bp, approximately 21.8X coverage and 104.2 M bp with an average read length of 589 bp and approximately 23.7X coverage were generated for the MTB-476 and MTB-489, respectively. The genome of MTB-476 consists of 257 contigs, 4204 CDS, 46 tRNAs and 3 rRNAs. MTB-489 has 187 contigs, 4183 CDS, 45 tRNAs and 3rRNAs.Conclusion: The results of genome assembling have been submitted into NCBI GenBank and are available for public access under the accession numbers AZBA00000000 and AZAZ00000000. These genome assemblies can be useful for comparative genome analysis and for identification of novel SNPs and gene variants in genomes of M.tuberculosis

Identifying risk factors associated with smear positivity of pulmonary tuberculosis in Kazakhstan

Background Sputum smear-positive tuberculosis (TB) patients have a high risk of transmission and are of great epidemiological and infection control significance. Little is known about the smearpositive populations in high TB burden regions, such as Kazakhstan. The objective of this study is to characterize the smear-positive population in Kazakhstan and identify associated modifiable risk factors. Methods Data on incident TB cases’ (identified between April 2012 and March 2014) socio-demographic, risk behavior, and comorbidity characteristics were collected in four regions of Kazakhstan through structured survey and medical record review. We used multivariable logistic regression to determine factors associated with smear positivity. Results Of the total sample, 193 (34.3%) of the 562 study participants tested smear-positive. In the final adjusted multivariable logistic regression model, sex (adjusted odds ratio (aOR) = 2.0, 95% CI:1.3–3.1, p < 0.01), incarceration (aOR = 3.6, 95% CI:1.2–11.1, p = 0.03), alcohol dependence (aOR = 2.6, 95% CI:1.2–5.7, p = 0.02), diabetes (aOR = 5.0, 95% CI:2.4–10.7, p < 0.01), and physician access (aOR = 2.7, 95% CI:1.3–5.5p < 0.01) were associated with smear-positivity. Conclusions Incarceration, alcohol dependence, diabetes, and physician access are associated with smear positivity among incident TB cases in Kazakhstan. To stem the TB epidemic, screening, treatment and prevention policies should address these factors

Draft genome sequences of two clinical Isolates of mycobacterium tuberculosis from sputum of Kazakh patients

Here, we report the draft genome sequences of two clinical isolates of Mycobacterium tuberculosis (MTB-476 and MTB-489) isolated from sputum of Kazakh patients

Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC’s genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value &lt; 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management

Distribution of Beijing Genotype Among Clinical Isolates of M. tuberculosis Circulating in Kazakhstan

Introduction. Methods of genotyping of M. tuberculosis play an important role in tuberсulosis (TB) infection control. These techniques are used to detect or exclude laboratory errors, control recurrent cases, and determine ways of TB transmission. Today, there are more than 10 methods of genotyping; MIRU-VNTR is one of the most widely used methods in the world. In this study we aimed to estimate biological diversity of clinical isolates of M. tuberculosis from different regions of Kazakhstan based on MIRU-VNTR analysis. Materials and methods. MIRU-VNTR was used to genotype 134 clinical isolates of M. tuberculosis isolated from new cases and recurrent cases of TB from different regions of Kazakhstan.  Amplification was done using 15 MIRU-VNTR loci. Determination of the number of tandem repeats in the corresponding locus was performed via Quantity One v.4.4.0 (BioRad, USA) software. H37Rv (NC_000962) reference strain was used as a positive control. Results. Phylogenic tree was built using www.miru-vntr.org web-resource based on the results of MIRU-VNTR analysis. Beijing family strains associated with drug resistance to antituberculosis drugs were prevalent among all isolates of M. tuberculosis circulating in Kazakhstan. Strains of the Beijing genotype were prevalent in both new cases (65%) and recurrent cases (89.4%) of tuberculosis. The second meaningful genotype that is spread in the territory of Kazakhstan is LAM, the frequency of distribution is 7.3% in new and 4.5% in recurrent cases. Other families of M. tuberculosis such as Ural, Haarlem, CAS, NEW-1, S were found in less than 4% of cases. Conclusion. Prevalence of Beijing family strains among all isolates of M. tuberculosis from different regions of Kazakhstan was shown. Strains of this family are prevalent among young people. This genotype is responsible for ongoing TB transmission in the present time. This genotype is more virulent; therefore, investigation of the epidemiology of the Beijing genotype plays crucial role in the monitoring of tuberculosis

GENETIC VARIANTS, METABOLOME, AND GUT MICROBIOME BIOMARKERS FOR OBESITY AND AGING IN RANDOMLY SELECTED KAZAKH INDIVIDUALS

Objective: Metabolic syndrome (MS) is a cluster of inter-related and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Genome, Metabolome variations and gut microbiome can predict disease risk and diagnosis and help to understand molecular pathophysiology. We aimed toassess plasma metabolom differences and gut microbiome as well as genetic variants among Kazakh population to identify and characterize the genetic, metabolic profiles and host-gut microbiota interactions. Methods: Kazakhs were recruited into study after signing of informed consent in Astana, Kazakhstan. Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) (Metabolon, USA) and NGS16S rRNA gene-sequence-based methods were used. Bioinformatic and statistical analyses were performed. Results: Subjects were stratified by age (young <45y, old ≥45y), gender and BMI. 853 different biochemical indicators of the main pathways for the metabolism were identified in plasma. Results demonstrate alterations in various metabolic pathways in older participants compared to younger subjects. Metabolic differences included changes in metabolites associated with the metabolism of fatty acids, steroidogenesis, secondary carnitine metabolism, inflammation and oxidative stress. Microbiomes of older persons are characterized by a high level of microorganisms involved in the processing of plant substrates, butyrate- producing bacteria and also has higher values of opportunistic microorganisms, representatives of the Tenericutes family. The biodiversity index of the microbiome of older persons is reduced in comparison with the biodiversity index in younger participants. This may indicate the influence on the microbiome characteristics of such factors as genotype, nutrition, lifestyle.Genetic risk factors associated with the obesity and hypertension were identified. Conclusions: Understanding plasma metabolome and gut microbiome is essential to the development of future personalized strategies of healthcare. Genome-wide association studies (GWAS) have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Further studies with detailed analysis are needed to clarify host-gut genetic and metbolome interactions. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (BR05236508)

THE EVALUATION OF CHROMOSOME TELOMERE LENGTH CHANGE AS A CRITERION OF LIFE EXPECTANCY IN BARIATRIC PRACTICE

In recent decades, the prevalence of obesity has been steadily increasing in most countries of the world. Overweight is a risk factor for a wide range of endocrine, cardiovascular, gastrointestinal, metabolic, neoplastic and musculoskeletal disorders and diseases. As you know, obesity is a state of chronic inflammation and severe oxidative stress, which will certainly affect the length of the chromosome telomeres. The dynamics of telomere length changes plays a decisive role in the regulation of cellu lar processes and cellular changes. Damage to telomeres, chromatin structures that help maintain the stability of the genome, leads to cell death or aging. However, information on how telomere length changes after weight loss through bariatric surgery remains limited to date. There are several types of bariatric surgery, each of which has its advantages and disadvantages. Based on this, it is possible that the restoration of the telomere length will differ depending on the technique used. This review de scribes the mechanisms for shortening leukocyte telomeres, and how bariatric surgery can affect this. The review also includes an analysis of evidence linking obesity and accelerated aging processes, as they are regulated by telomere

An AutoML Approach for Predicting Risk of Progression to Active Tuberculosis based on Its Association with Host Genetic Variations

Tuberculosis (TB) is a worldwide health challenge. Mycobacterium tuberculosis(M.tb) is capable of evading the host immune system which can lead to tuberculosis infection. Household contacts (HHCs) of TB cases have a higher risk of infection. Novel predictive techniques to identify high-risk TB susceptible groups are needed. Susceptibility to Tuberculosis is associated with host genetic variations. This research work uses the TPOT autoML tool to map genetic variations and TB infection status mathematically. Machine learning was employed to predict the risk of progression to active tuberculosis based on associated host genetic variation. Among the three adopted configurations, TPOT Default , TPOT spars , TPOT N that were used, TPOT Default, and TPOT sparse produced the same best performance both reaching 0.816 Training CV score and 0.625 Testing Accuracy. Different genes variants identified using this approach were found to have distinctive contributions for TB infection, which represent the feature importance of the classifier. The feature importance of the random forest classifier pipeline in TPOT sparse was adopted. The top ten contributing genes were also submitted to Enrichr for gene pathway enrichment analysis. The identified enriched pathways have been shown to be key to TB infection