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126 Publications visible to you, out of a total of 126
Space flight associated changes in astronauts’ plasma‐derived small extracellular vesicle microRNA: Biomarker identification

Abstract (Expand)

Dear Editor, This pilot study suggests relatively short (median 12 days long) low-Earth orbit (LEO) spaceflight induces changes in circulating plasma small extracellular vesicle (sEV) microRNA expression. … Normalization of small RNA sequencing (sRNAseq) data and quantitative polymerase chain reaction (qPCR) validation confirmed miR-4732-3p is significantly upregulated up to 3 days post-landing, and enrichment analysis suggests this miRNA is expressed in various central nervous system tissues and hematopoietic cells and may be linked to different organ disorders.

Authors: David Goukassian, Arsen Arakelyan, Agnieszka Brojakowska, Malik Bisserier, Siras Hakobyan, Lahouaria Hadri, Amit Kumar Rai, Angela Evans, Aimy Sebastian, May Truongcao, Carolina Gonzalez, Anamika Bajpai, Zhongjian Cheng, Praveen Kumar Dubey, Sankar Addya, Paul Mills, Kenneth Walsh, Raj Kishore, Matt Coleman, Venkata Naga Srikanth Garikipati

Date Published: 2nd Jun 2022

Publication Type: Journal

Antiviral activity of brequinar against African swine fever virus infection in vitro.

Abstract (Expand)

African swine fever virus (ASFV) is a double-stranded DNA virus that causes an acute and hemorrhagic disease in domestic swine, resulting in significant economic losses to the global porcine industry. … The lack of vaccines and antiviral drugs highlights the urgent need for antiviral studies against ASFV. Here, we report that brequinar (BQR), which is a specific inhibitor of dihydroorotate dehydrogenase, robustly inhibits ASFV replication in Vero cells, as well as in porcine macrophages. We demonstrate that BQR exerts its antiviral activity in a dose-dependent manner through the depletion of pyrimidine pool. Although BQR does not affect the synthesis of an early viral protein, pI215L, the synthesis of late viral proteins, p17 and p72, is suppressed in the presence of BQR. We also show that BQR is able to induce cellular antiviral response in ASFV-infected macrophages by enhancing the expression of interferon-stimulated genes. Taken together, our study reveals that targeting nucleotide biosynthesis represents a promising strategy for developing antiviral agents against ASFV.

Authors: Rafayela Grigoryan, Erik Arabyan, Roza Izmailyan, Zaven Karalyan, Nuno Jordão, Fernando Ferreira, Hovakim Zakaryan

Date Published: 23rd May 2022

Publication Type: Journal

Molecular Analysis of SARS-CoV-2 Lineages in Armenia

Abstract (Expand)

The sequencing of SARS-CoV-2 provides essential information on viral evolution, transmission, and epidemiology. In this paper, we performed the whole-genome sequencing of SARS-CoV-2 using nanopore and … Illumina sequencing to describe the circulation of the virus lineages in Armenia. The analysis of 145 full genomes identified six clades (19A, 20A, 20B, 20I, 21J, and 21K) and considerable intra-clade PANGO lineage diversity. Phylodynamic and transmission analysis allowed to attribute specific clades as well as infer their importation routes. Thus, the first two waves of positive case increase were caused by the 20B clade, the third peak caused by the 20I (Alpha), while the last two peaks were caused by the 21J (Delta) and 21K (Omicron) variants. The functional analyses of mutations in sequences largely affected epitopes associated with protective HLA loci and did not cause the loss of the signal in PCR tests targeting ORF1ab and N genes as confirmed by RT-PCR. We also compared the performance of nanopore and Illumina short-read sequencing and showed the utility of nanopore sequencing as an efficient and affordable alternative for large-scale molecular epidemiology research. Thus, our paper describes new data on the genomic diversity of SARS-CoV-2 variants in Armenia in the global context of the virus molecular genomic surveillance.

Authors: Diana Avetyan, Siras Hakobyan, Maria Nikoghosyan, Lilit Ghukasyan, Gisane Khachatryan, Tamara Sirunyan, Nelli Muradyan, Roksana Zakharyan, Andranik Chavushyan, Varduhi Hayrapetyan, Anahit Hovhannisyan, Shah A. Mohamed Bakhash, Keith R. Jerome, Pavitra Roychoudhury, Alexander L. Greninger, Lyudmila Niazyan, Mher Davidyants, Gayane Melik-Andreasyan, Shushan Sargsyan, Lilit Nersisyan, Arsen Arakelyan

Date Published: 17th May 2022

Publication Type: Journal

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

Abstract (Expand)

The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte … antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine. The present study aimed at detecting associations between common HLA alleles and COVID-19 susceptibility and severity in Armenians. In 299 COVID-19 patients (75 asymptomatic, 102 mild/moderate, 122 severe), the association between disease severity and classic HLA-I and II loci was examined. We found that the advanced age, male sex of patients, and sex and age interaction significantly contributed to the severity of the disease. We observed that an age-dependent effect of HLA-B*51:01 carriage [odds ratio (OR)=0.48 (0.28-0.80), Pbonf <0.036] is protective against severe COVID-19. Contrary, the HLA-C*04:01 allele, in a dose-dependent manner, was associated with a significant increase in the disease severity [OR (95% CI) =1.73 (1.20-2.49), Pbonf <0.021] and an advancing age (P<0.013). The link between HLA-C*04:01 and age was secondary to a stronger association between HLA-C*04:01 and disease severity. However, HLA-C*04:01 exerted a sex-dependent differential distribution between clinical subgroups [females: P<0.0012; males: P=0.48]. The comparison of HLA-C*04:01 frequency between subgroups and 2,781 Armenian controls revealed a significant incidence of HLA-C*04:01 deficiency in asymptomatic COVID-19. HLA-C*04:01 homozygous genotype in patients blueprinted a decrease in heterozygosity of HLA-B and HLA class-I loci. In HLA-C*04:01 carriers, these changes translated to the SARS-CoV-2 peptide presentation predicted inefficacy by HLA-C and HLA class-I molecules, simultaneously enhancing the appropriate HLA-B potency. In patients with clinical manifestation, due to the high prevalence of HLA-C*04:01, these effects provided a decrease of the HLA class-I heterozygosity and an ability to recognize SARS-CoV-2 peptides. Based on our observations, we developed a prediction model involving demographic variables and HLA-C*04:01 allele for the identification of potential cases with the risk of hospitalization (the area under the curve (AUC) = 86.2%) or severe COVID-19 (AUC =71%).

Authors: Anahit Hovhannisyan, Vergine Madelian, Sevak Avagyan, Mihran Nazaretyan, Armine Hyussyan, Alina Sirunyan, Rubina Arakelyan, Zorayr Manukyan, Levon Yepiskoposyan, Karine R. Mayilyan, Frieda Jordan

Date Published: 3rd Feb 2022

Publication Type: Journal

The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders.

Abstract (Expand)

Mutually linked expression and methylation dynamics in the brain govern genome regulation over the whole lifetime with an impact on cognition, psychological disorders, and cancer. We performed a joint … study of gene expression and DNA methylation of brain tissue originating from the human prefrontal cortex of individuals across the lifespan to describe changes in cellular programs and their regulation by epigenetic mechanisms. The analysis considers previous knowledge in terms of functional gene signatures and chromatin states derived from independent studies, aging profiles of a battery of chromatin modifying enzymes, and data of gliomas and neuropsychological disorders for a holistic view on the development and aging of the brain. Expression and methylation changes from babies to elderly adults decompose into different modes associated with the serial activation of (brain) developmental, learning, metabolic and inflammatory functions, where methylation in gene promoters mostly represses transcription. Expression of genes encoding methylome modifying enzymes is very diverse reflecting complex regulations during lifetime which also associates with the marked remodeling of chromatin between permissive and restrictive states. Data of brain cancer and psychotic disorders reveal footprints of pathophysiologies related to brain development and aging. Comparison of aging brains with gliomas supports the view that glioblastoma-like and astrocytoma-like tumors exhibit higher cellular plasticity activated in the developing healthy brain while oligodendrogliomas have a more stable differentiation hierarchy more resembling the aged brain. The balance and specific shifts between volatile and stable and between more irreversible and more plastic epigenomic networks govern the development and aging of healthy and diseased brain.

Authors: H. Loeffler-Wirth, L. Hopp, M. Schmidt, R. Zakharyan, A. Arakelyan, H. Binder

Date Published: 21st Jan 2022

Publication Type: Journal

Emerging Role of Exosomal Long Non-coding RNAs in Spaceflight-Associated Risks in Astronauts

Abstract (Expand)

During spaceflight, astronauts are exposed to multiple unique environmental factors, particularly microgravity and ionizing radiation, that can cause a range of harmful health consequences. Over the … past decades, increasing evidence demonstrates that the space environment can induce changes in gene expression and RNA processing. Long non-coding RNA (lncRNA) represent an emerging area of focus in molecular biology as they modulate chromatin structure and function, the transcription of neighboring genes, and affect RNA splicing, stability, and translation. They have been implicated in cancer development and associated with diverse cardiovascular conditions and associated risk factors. However, their role on astronauts' health after spaceflight remains poorly understood. In this perspective article, we provide new insights into the potential role of exosomal lncRNA after spaceflight. We analyzed the transcriptional profile of exosomes isolated from peripheral blood plasma of three astronauts who flew on various Shuttle missions between 1998-2001 by RNA-sequencing. Computational analysis of the transcriptome of these exosomes identified 27 differentially expressed lncRNAs with a Log2 fold change, with molecular, cellular, and clinical implications.

Authors: Malik Bisserier, Nathaniel Saffran, Agnieszka Brojakowska, Aimy Sebastian, Angela Clare Evans, Matthew A. Coleman, Kenneth Walsh, Paul J. Mills, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, Lahouaria Hadri, David A. Goukassian

Date Published: 17th Jan 2022

Publication Type: Journal

Projection of High-Dimensional Genome-Wide Expression on SOM Transcriptome Landscapes

Abstract (Expand)

organizing maps portraying has been proven to be a powerful approach for analysis of transcriptomic, genomic, epigenetic, single-cell, and pathway-level data as well as for “multi-omic” integrative … analyses. However, the SOM method has a major disadvantage: it requires the retraining of the entire dataset once a new sample is added, which can be resource- and time-demanding. It also shifts the gene landscape, thus complicating the interpretation and comparison of results. To overcome this issue, we have developed two approaches of transfer learning that allow for extending SOM space with new samples, meanwhile preserving its intrinsic structure. The extension SOM (exSOM) approach is based on adding secondary data to the existing SOM space by “meta-gene adaptation”, while supervised SOM portrayal (supSOM) adds support vector machine regression model on top of the original SOM algorithm to “predict” the portrait of a new sample. Both methods have been shown to accurately combine existing and new data. With simulated data, exSOM outperforms supSOM for accuracy, while supSOM significantly reduces the computing time and outperforms exSOM for this parameter. Analysis of real datasets demonstrated the validity of the projection methods with independent datasets mapped on existing SOM space. Moreover, both methods well handle the projection of samples with new characteristics that were not present in training datasets.

Authors: Maria Nikoghosyan, Henry Loeffler-Wirth, Suren Davidavyan, Hans Binder, Arsen Arakelyan

Date Published: 27th Dec 2021

Publication Type: Journal

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