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93 Publications visible to you, out of a total of 93
Molecular Epidemiology and In-Depth Characterization of Klebsiella pneumoniae Clinical Isolates from Armenia

Abstract (Expand)

The global dissemination of Klebsiella pneumoniae pathotypes with multidrug-resistant (MDR) and hypervirulent traits poses a threat to public health. The situation in Armenia is unclear, and we performed … a comprehensive characterisation of 48 clinical isolates of K. pneumoniae, collected from 2018 to 2024. The majority of the isolates (64.58%) were extensively drug-resistant (XDR) and MDR. Genomic analysis of 21 isolates revealed the presence of international high-risk MDR clones (ST395, ST15, and ST307). The ST395 strains were isolated from children and resisted the first-line drugs such as beta-lactams. These isolates harboured a range of virulence determinants, from capsule polysaccharides to siderophores to regulators of the mucoid phenotype. The ST395 strains are enriched by ICEs, plasmids, and prophages, on which antimicrobial resistance (AMR) and virulence genes are located and which may lead to the convergence of MDR and hypervirulent traits. There is a widespread non-specific AMR mechanism among our K. pneumoniae strains. These are mutations in the porin genes, which reduce permeability to antimicrobials, and mutations in the regulators of efflux pumps, which lead to overexpression of drug efflux pumps such as AcrAB. These mechanisms may contribute to the elevated MICs and confer AMR to strains with no specific AMR genes.

Authors: Anahit Sedrakyan, Zaruhi Gevorgyan, Magdalina Zakharyan, Karine Arakelova, Shoghik Hakobyan, Alvard Hovhannisyan, Rustam Aminov

Date Published: 9th Jan 2025

Publication Type: Journal

Evaluating sex-specific responses to western diet across the lifespan: impact on cardiac function and transcriptomic signatures in C57BL/6J mice at 530 and 640/750 days of age.

Abstract (Expand)

BACKGROUND: Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term … effects of WD on the pathophysiology of CVD and sex-specific responses. METHODS: Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days. RESULTS: In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life. In male mice, ECHO revealed the development of an HFrEF-like phenotype later in life without detectable structural alterations. The transcriptomic profile revealed a sex-associated dichotomy in LV structure and function. Specifically, at 530-day, WD-fed male mice exhibited differentially expressed genes (DEGs), which were overrepresented in pathways associated with endocrine function, signal transduction, and cardiomyopathies. At 750 days, WD-fed male mice exhibited dysregulation of several genes involved in various lipid, glucagon, and glutathione metabolic pathways. At 530 days, WD-fed female mice exhibited the most distinctive set of DEGs with an abundance of genes related to circadian rhythms. At 640 days, altered DEGs in WD-fed female mice were associated with cardiac energy metabolism and remodeling. CONCLUSIONS: Our study demonstrated distinct sex-specific and age-associated differences in cardiac structure, function, and transcriptome signature between WD-fed male and female mice.

Authors: A. Stepanyan, A. Brojakowska, R. Zakharyan, S. Hakobyan, S. Davitavyan, T. Sirunyan, G. Khachatryan, M. K. Khlgatian, M. Bisserier, S. Zhang, S. Sahoo, L. Hadri, A. Rai, V. N. S. Garikipati, A. Arakelyan, D. A. Goukassian

Date Published: 28th Dec 2024

Publication Type: Journal

Association of Inflammasome Gene Expression Levels with Pathogenesis of Familial Mediterranean Fever in Armenians

Abstract (Expand)

Mediterranean fever (FMF) is a genetically determined autoinflammatory disease transmitted mostly by an autosomal recessive mechanism and caused by point mutations of the MEFV (Mediterranean FeVer) … gene. The aim of this study was to evaluate the expression of inflammasome genes (p65, Casp1, MEFV, and NLRP3) in patients with FMF compared to controls to understand the changes playing a key role in disease development. We found altered expression levels of the full-length MEFV isoform as well as Casp1 and p65 in FMF patients versus controls. This, once again, highlighted the significance of inflammasome genes in terms of FMF.

Authors: Varduhi Hayrapetyan, Lana Karapetyan, Lilit Ghukasyan, Sofi Atshemyan, Hovsep Ghazaryan, Valentina Vardanyan, Vahan Mukuchyan, Arsen Arakelyan, Roksana Zakharyan

Date Published: 2nd Dec 2024

Publication Type: Journal

Genewise detection of variants in MEFV gene using nanopore sequencing

Abstract (Expand)

Mediterranean Fever (FMF) is a genetic disorder with complex inheritance patterns and genotype-phenotype associations, and it is highly prevalent in Armenia. FMF typically follows an autosomal recessive … inheritance pattern (OMIM: 249100), though it can occasionally display a rare dominant inheritance pattern with variable penetrance (OMIM։134610). The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein. While the 26 most prevalent mutations account for nearly 99% of all FMF cases, more than 60 pathogenic mutations have been identified. In this study, we aimed to develop an affordable nanopore sequencing method for full-length MEFV gene mutation detection to aid in the diagnosis and screening of FMF. We employed a multiplex amplicon sequencing approach, allowing for the processing of up to 12 samples on both Flow cells and Flongle flow cells. The results demonstrated near-complete concordance between nanopore variant calling and qPCR genotypes. Moreover, nanopore sequencing identified additional variants, which were confirmed by whole exome sequencing. Additionally, intronic and UTR variants were detected. Our findings demonstrate the feasibility of full-gene nanopore sequencing for detecting FMF-associated pathogenic variants. The method is cost-effective, with costs comparable to those of the qPCR test, making it particularly suitable for settings with limited laboratory infrastructure. Further clinical validation using larger sample cohorts will be necessary.

Authors: Lilit Ghukasyan, Gisane Khachatryan, Tamara Sirunyan, Arpine Minasyan, Siras Hakobyan, Andranik Chavushyan, Varduhi Hayrapetyan, Hovsep Ghazaryan, Gevorg Martirosyan, Gohar Mkrtchyan, Valentina Vardanyan, Vahan Mukuchyan, Ashot Davidyants, Roksana Zakharyan, Arsen Arakelyan

Date Published: 29th Nov 2024

Publication Type: Journal

Demographic history and genetic variation of the Armenian population

Abstract (Expand)

We introduce a sizable (n = 34) whole-genome dataset on Armenians, a population inhabiting the region in West Asia known as the Armenian highlands. Equipped with this genetic data, we conducted a … whole-genome study of Armenians and deciphered their fine-scale population structure and complex demographic history. We demonstrated that the Armenian populations from western, central, and eastern parts of the highlands are relatively homogeneous. The Sasun, a population in the south that had been argued to have received a major genetic contribution from Assyrians, was instead shown to have derived its slightly divergent genetic profile from a bottleneck that occurred in the recent past. We also investigated the debated question on the genetic origin of Armenians and failed to find any significant support for historical suggestions by Herodotus of their Balkan-related ancestry. We checked the degree of continuity of modern Armenians with ancient inhabitants of the eastern Armenian highlands and detected a genetic input into the region from a source linked to Neolithic Levantine Farmers at some point after the Early Bronze Age. Additionally, we cataloged an abundance of new mutations unique to the population, including a missense mutation predicted to cause familial Mediterranean fever, an autoinflammatory disorder highly prevalent in Armenians. Thus, we highlight the importance of further genetic and medical studies of this population.

Authors: Anahit Hovhannisyan, Pierpaolo Maisano Delser, Anna Hakobyan, Eppie R. Jones, Joshua G. Schraiber, Mariya Antonosyan, Ashot Margaryan, Zhe Xue, Sungwon Jeon, Jong Bhak, Peter Hrechdakian, Hovhannes Sahakyan, Lehti Saag, Zaruhi Khachatryan, Levon Yepiskoposyan, Andrea Manica

Date Published: 25th Nov 2024

Publication Type: Journal

Unveiling Iso- and Aniso-Hydric Disparities in Grapevine-A Reanalysis by Transcriptome Portrayal Machine Learning.

Abstract (Expand)

Mechanisms underlying grapevine responses to water(-deficient) stress (WS) are crucial for viticulture amid escalating climate change challenges. Reanalysis of previous transcriptome data uncovered … disparities among isohydric and anisohydric grapevine cultivars in managing water scarcity. By using a self-organizing map (SOM) transcriptome portrayal, we elucidate specific gene expression trajectories, shedding light on the dynamic interplay of transcriptional programs as stress duration progresses. Functional annotation reveals key pathways involved in drought response, pinpointing potential targets for enhancing drought resilience in grapevine cultivation. Our results indicate distinct gene expression responses, with the isohydric cultivar favoring plant growth and possibly stilbenoid synthesis, while the anisohydric cultivar engages more in stress response and water management mechanisms. Notably, prolonged WS leads to converging stress responses in both cultivars, particularly through the activation of chaperones for stress mitigation. These findings underscore the importance of understanding cultivar-specific WS responses to develop sustainable viticultural strategies in the face of changing climate.

Authors: T. Konecny, A. Asatryan, M. Nikoghosyan, H. Binder

Date Published: 6th Sep 2024

Publication Type: Journal

Pan-cancer analysis of telomere maintenance mechanisms.

Abstract (Expand)

Telomeres, protective caps at chromosome ends, maintain genomic stability and control cell lifespan. Dysregulated telomere maintenance mechanisms (TMMs) are cancer hallmarks, enabling unchecked cell … proliferation. We conducted a pan-cancer evaluation of TMM using RNA sequencing data from The Cancer Genome Atlas for 33 different cancer types and analyzed the activities of telomerase-dependent (TEL) and alternative lengthening of telomeres (ALT) TMM pathways in detail. To further characterize the TMM profiles, we categorized the tumors based on their ALT and TEL TMM pathway activities into five major phenotypes: ALT (high) TEL (low), ALT (low) TEL (low), ALT (middle) TEL (middle), ALT (high) TEL (high), and ALT (low) TEL (high). These phenotypes refer to variations in telomere maintenance strategies, shedding light on the heterogeneous nature of telomere regulation in cancer. Moreover, we investigated the clinical implications of TMM phenotypes by examining their associations with clinical characteristics and patient outcomes. Specific TMM profiles were linked to specific survival patterns, emphasizing the potential of TMM profiling as a prognostic indicator and aiding in personalized cancer treatment strategies. Gene ontology analysis of the TMM phenotypes unveiled enriched biological processes associated with cell cycle regulation (both TEL and ALT), DNA replication (TEL), and chromosome dynamics (ALT) showing that telomere maintenance is tightly intertwined with cellular processes governing proliferation and genomic stability. Overall, our study provides an overview of the complexity of transcriptional regulation of telomere maintenance mechanisms in cancer.

Authors: M. Hakobyan, H. Binder, A. Arakelyan

Date Published: 2nd Jul 2024

Publication Type: Journal

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