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7 Publications visible to you, out of a total of 7
The effects of space radiation on the transcriptome of heart right ventricle tissue

Abstract (Expand)

Deep space represents a challenging environment for human exploration and can be accompanied by harmful health-related risks. We aimed to assess the effect of simplified galactic cosmic ray simulated … (simGCRsim) and gamma (γ) ionizing radiation (IR) on transcriptome changes in right ventricular (RV) tissue after a single low dose (0.5 Gy, 500 MeV/nucleon) full body exposure in C57BL/6J male and female mice. In females, no differentially expressed genes (DEGs) and only 2 upregulated genes in males exposed to γ-IR were revealed. In contrast, exposure to simGCRsim-IR resulted in 4 DEGs in females and 371 DEGs in males, suggesting longer-lasting and sex-biased DEGs after simGCRsim-IR. Overrepresentation analysis of DEGs in simGCRsim-IR males revealed significant enrichment in pathways related to muscle contraction, hypertrophic cardiomyopathy, oxytocin release, the regulation of cytoskeleton, and genes associated with Alzheimer’s, Huntington’s, and Parkinson’s diseases. Our results suggested the RV transcriptome exhibits distinct responses after exposure based on both the IR and sex.

Authors: Roksana Zakharyan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Shihong Zhang, Mary K. Khlgatian, Amit Kumar Rai, Suren Davitavyan, Ani Stepanyan, Tamara Sirunyan, Gisane Khachatryan, Susmita Sahoo, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, David A. Goukassian

Date Published: 21st Jul 2025

Publication Type: Journal

Long-lasting sex-specific alteration in left ventricular cardiac transcriptome following gamma and simGCRsim radiation

Abstract (Expand)

Space irradiation (IR) is an important health risk for deep-space missions. We reported heart failure with preserved ejection fraction like cardiac phenotype 660-days following exposure to a single-dose … of a simplified galactic cosmic ray simulation (simGCRsim) only in males with functional and structural impairment in left ventricular (LV) function. This sex-based dichotomy prompted us to investigate sex-specific changes in the LV transcriptome in three-month-old male and female mice exposed to 137Cs-γ- or simGCRsim-IR. Non-IR male and female (10 each) mice served as controls. LVs were collected at 440/660- and 440/550-days post-IR, male and female, respectively. RNA sequencing, differential gene expression, and functional annotation were performed on tissues from 5 mice/group. Sex and post-IR time points had the greatest influence on gene expression, surpassing the IR-type effects. SimGCRsim-IR showed more persistent transcriptome changes than γ-IR. We suggest that the single IR effects can persist up to 550-660 days, with overwhelmingly sex-biased responses at individual gene expression level.

Authors: Roksana Zakharyan, Siras Hakobyan, Agnieszka Brojakowska, Suren Davitavyan, Ani Stepanyan, Tamara Sirunyan, Gisane Khachatryan, Mary K. Khlgatian, Malik Bisserier, Shihong Zhang, Susmita Sahoo, Lahouaria Hadri, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, David A. Goukassian

Date Published: 18th Feb 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

Long-term environmental metal exposure is associated with hypomethylation of CpG sites in NFKB1 and other genes related to oncogenesis.

Abstract (Expand)

BACKGROUND: Long-term environmental exposure to metals leads to epigenetic changes and may increase risks to human health. The relationship between the type and level of metal exposure and epigenetic … changes in subjects exposed to high concentrations of metals in the environment is not yet clear. The aim of our study is to find the possible association of environmental long-term exposure to metals with DNA methylation changes of genes related to immune response and carcinogenesis. We investigated the association of plasma levels of 21 essential and non-essential metals detected by ICP-MS and the methylation level of 654 CpG sites located on NFKB1, CDKN2A, ESR1, APOA5, IGF2 and H19 genes assessed by targeted bisulfite sequencing in a cohort of 40 subjects living near metal mining area and 40 unexposed subjects. Linear regression was conducted to find differentially methylated positions with adjustment for gender, age, BMI class, smoking and metal concentration. RESULTS: In the metal-exposed group, five CpGs in the NFKB1 promoter region were hypomethylated compared to unexposed group. Four differentially methylated positions (DMPs) were associated with multiple metals, two of them are located on NFKB1 gene, and one each on CDKN2A gene and ESR1 gene. Two DMPs located on NFKB1 (chr4:102500951, associated with Be) and IGF2 (chr11:2134198, associated with U) are associated with specific metal levels. The methylation status of the seven CpGs located on NFKB1 (3), ESR1 (2) and CDKN2A (2) positively correlated with plasma levels of seven metals (As, Sb, Zn, Ni, U, I and Mn). CONCLUSIONS: Our study revealed methylation changes in NFKB1, CDKN2A, IGF2 and ESR1 genes in individuals with long-term human exposure to metals. Further studies are needed to clarify the effect of environmental metal exposure on epigenetic mechanisms and pathways involved.

Authors: A. Stepanyan, A. Petrackova, S. Hakobyan, J. Savara, S. Davitavyan, E. Kriegova, A. Arakelyan

Date Published: 7th Aug 2023

Publication Type: Journal

Integrated Multi-Omics Maps of Lower-Grade Gliomas.

Abstract (Expand)

Multi-omics high-throughput technologies produce data sets which are not restricted to only one but consist of multiple omics modalities, often as patient-matched tumour specimens. The integrative … analysis of these omics modalities is essential to obtain a holistic view on the otherwise fragmented information hidden in this data. We present an intuitive method enabling the combined analysis of multi-omics data based on self-organizing maps machine learning. It "portrays" the expression, methylation and copy number variations (CNV) landscapes of each tumour using the same gene-centred coordinate system. It enables the visual evaluation and direct comparison of the different omics layers on a personalized basis. We applied this combined molecular portrayal to lower grade gliomas, a heterogeneous brain tumour entity. It classifies into a series of molecular subtypes defined by genetic key lesions, which associate with large-scale effects on DNA methylation and gene expression, and in final consequence, drive with cell fate decisions towards oligodendroglioma-, astrocytoma- and glioblastoma-like cancer cell lineages with different prognoses. Consensus modes of concerted changes of expression, methylation and CNV are governed by the degree of co-regulation within and between the omics layers. The method is not restricted to the triple-omics data used here. The similarity landscapes reflect partly independent effects of genetic lesions and DNA methylation with consequences for cancer hallmark characteristics such as proliferation, inflammation and blocked differentiation in a subtype specific fashion. It can be extended to integrate other omics features such as genetic mutation, protein expression data as well as extracting prognostic markers.

Authors: H. Binder, M. Schmidt, L. Hopp, S. Davitavyan, A. Arakelyan, H. Loeffler-Wirth

Date Published: 4th Jun 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

SARS-CoV-2 detection by extraction-free qRT-PCR for massive and rapid COVID-19 diagnosis during a pandemic in Armenia

Abstract (Expand)

COVID-19 pandemic severely impacted the healthcare and economy on a global scale. It is widely recognized that mass testing is an efficient way to contain the spread of SARS-CoV-2 infection as well as … aid in the development of informed policies for disease management. However, the current COVID-19 worldwide infection rates increased the demand for rapid and reliable screening of infection. We compared the performance of qRT-PCR in direct heat-inactivated (H), heat-inactivated and pelleted (HC) samples against RNA in a group of 74 subjects (44 positive and 30 negative). Then we compared the sensitivity of HC in a larger group of 196 COVID-19 positive samples. Our study suggests that HC samples show higher accuracy for SARS-CoV-2 detection PCR assay compared to direct H (89 % vs 83 % of the detection in RNA). The sensitivity of detection using direct samples varied depending on the sample transport and storage media as well as the viral loads (as measured by qRT-PCR Ct levels). Altogether, all the data suggest that purified RNA provides more accurate results, however, direct sample testing with qRT-PCR may help to significantly increase testing capacity. Switching to the direct sample testing is justified if the number of tests is doubled at least.

Authors: Diana Avetyan, Andranik Chavushyan, Hovsep Ghazaryan, Ani Melkonyan, Ani Stepanyan, Roksana Zakharyan, Varduhi Hayrapetyan, Sofi Atshemyan, Gisane Khachatryan, Tamara Sirunyan, Suren Davitavyan, Gevorg Martirosyan, Gayane Melik-Andreasyan, Shushan Sargsyan, Armine Ghazazyan, Naira Aleksanyan, Xiushan Yin, Arsen Arakelyan

Date Published: No date defined

Publication Type: Journal

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