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140 Publications visible to you, out of a total of 140
Long-term Pathway Activation in Cardiac Ventricular Tissues after Gamma and simGCRsim Irradiation.

Abstract (Expand)

Space radiation represents a significant health risk for deep-space exploration, yet its long-term effects on cardiovascular function remain poorly understood. While our previous studies have highlighted … persistent transcriptional changes in left ventricular (LV) and right ventricular (RV) tissues after a single whole-body irradiation in mice, a systems-level understanding of pathway activity deregulation is lacking. To address this gap, we applied the Pathway Signal Flow (PSF) algorithm to analyze long-term pathway activity alterations in LV and RV tissues of C57Bl/6J mice exposed to gamma radiation (100 cGy 137Cs) or the simplified Galactic Cosmic Ray simulation (simGCRsim, 50 cGy 500 MeV/n) composition of ion beams. RNA sequencing data were analyzed to assess pathway activity changes, sex-specific effects, and ventricular differences 440 days post-irradiation. We observed marked sex- and ventricle-specific differences in pathway deregulation. Left ventricular tissues in females exhibited broad signaling pathway alterations after simGCRsim exposure, particularly in immune response, cytoskeletal remodeling, and survival-related pathways (e.g., NF-κB, VEGF, and MAPK). In contrast, male RV tissues demonstrated higher pathway deregulation than LV, particularly in PPAR, NF-κB, and HIF-1 pathways, implicating metabolic disruption and survival adaptations. Furthermore, simGCRsim exposure induced greater long-term pathway perturbations than gamma rays. Our findings suggest that sex-dependent and ventricle-specific signaling alterations contribute to long-term cardiovascular risks following space irradiation. Notably, VEGF and NF-κB signaling emerge as key regulators of cardiac adaptation in females. Future studies in larger cohorts, incorporating early-stage molecular responses and broader pathway analyses, are needed to refine cardiovascular risk assessments for space travel.

Authors: Gisane Khachatryan, Tamara Sirunyan, Siras Hakobyan, Suren Davitavyan, Roksana Zakharyan, Ani Stepanyan, Agnieszka Brojakowska, Mary K Khlgatian, Malik Bisserier, Shihong Zhang, David A Goukassian, Arsen Arakelyan

Date Published: 25th Sep 2025

Publication Type: Journal

Spatial transcriptome analysis of the human eyelid depicts meibomian gland cell differentiation: A pilot study.

Abstract (Expand)

Meibomian glands (MGs) are an integral component of the ocular defense system, as their secretion product, meibum, is essential for protecting the eye surface. To characterize the transcriptional program … underlying meibum production, we employed spatial transcriptomics (ST) analysis of the human eyelid from a sample from a 60-year-old male. We resolved 18 distinct eyelid clusters, representing structures such as the conjunctiva, epidermis, hair-associated sebaceous glands, and MGs. Focusing on the MG, we distinguished basal (MEI-B cluster) and differentiating (MEI-DIFF cluster) meibocytes, as well as a third, duct-related cluster (MEI-DUCT). Self-organizing maps (SOM) portrayal of ST images and pseudotime analysis confirmed progress from MEI-B to MEI-DIFF and further to MEI-DUCT, as the latter turned out to include terminally differentiated meibocytes. Accordingly, gene set enrichment analysis associated early/intermediate meibocyte maturation with energy and lipid metabolism, and later stages with barrier functions. We also identified significant differences between the MG and sebaceous gland transcriptomes. The MG-specific signature included transcripts such as AQP9, MMP3, and PITX1, and selective expression of PITX1 in the MG compared to the sebaceous gland was confirmed by immunohistochemistry on the same sample and samples from three other elderly adults. We deliver the first spatial portrait of the human MG transcriptional landscape. Besides enhancing our understanding of MG physiology, our study identifies novel targets for regulating MG homeostasis in health and disease.

Authors: H. Binder, U. Hampel, H. Loeffler-Wirth, F. Hansmann, H. Pfannkuche, M. Schmidt, M. R. Schneider

Date Published: 19th Sep 2025

Publication Type: Journal

Responding to Stress: Diversity and Resilience of Grapevine in a Changing Climate Under the Perspective of Omics Research

Abstract (Expand)

hange, with its altered precipitation and extreme temperatures, significantly threatens global viticulture by affecting grapevine growth, yield, and fruit quality. Understanding the molecular underpinnings … of grapevine resilience is crucial for developing adaptive strategies. Our aim is to explore the application of multi-omics approaches (integrating genomics, transcriptomics, proteomics, metabolomics, and epigenetics) to investigate grapevine stress responses. Advances in these omics technologies have been pivotal in identifying key stress-response genes, metabolic pathways, and regulatory networks, particularly those contributing to grapevine tolerance to water deficiency, (such as drought and decreased precipitation), extreme temperatures, UV radiation, and salinity. Furthermore, the rich genetic reservoir within grapevines serves as a vital resource for enhancing stress tolerance. While adaptive strategies such as rootstock selection and precision irrigation are important, future research must prioritize integrated multi-omics studies, including those on regional climate adaptation and long-term breeding programs. Such efforts are essential to exploit genetic diversity and ensure the sustainability of viticulture in the evolving climate. In summary, this review demonstrates how utilizing the inherent genetic variability of grapevines and employing multi-omics approaches are critical for understanding and enhancing their resilience to the challenges posed by climate change.

Authors: Tomas Konecny, Armine Asatryan, Hans Binder

Date Published: 15th Aug 2025

Publication Type: Journal

Topology-aware pathway analysis of spatial transcriptomics

Abstract (Expand)

Spatial transcriptomics (ST) has transformed genomics by mapping gene expression onto intact tissue architecture, uncovering intricate cellular interactions that bulk and single-cell RNA sequencing … often overlook. Traditional ST workflows typically involve clustering spots, performing differential expression analyses, and annotating results via gene-set methods such as overrepresentation analysis (ORA) or gene set enrichment analysis (GSEA). More recent spatially-aware techniques extend these approaches by incorporating tissue organization into gene-set scoring. However, because they operate primarily at the level of individual genes, they may overlook the connectivity and topology of biological pathways, limiting their capacity to trace the propagation of signaling events within tissue regions. In this study, we address that gap by translating gene expression into pathway-level activity using the Pathway Signal Flow (PSF) algorithm. PSF integrates expression data with curated interaction networks to compute numeric activity scores for each branch of a biological pathway, producing a functionally annotated feature space that captures downstream signaling effects as branch-specific activity values. We applied PSF to two public 10x Genomics Visium datasets (human melanoma and mouse brain) and compared clustering based on PSF-derived pathway activities from 40 curated Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene expression with standard Seurat Louvain clustering and spatially aware methods (Vesalius, spatialGE). We observed good correspondence between PSF-based and expression-based clustering when spatially aware clustering methods were used. This suggests that branch-level pathway activities can themselves drive clustering and pinpoint spatially deregulated processes. To assess cluster-specific functional annotation, we compared PSF results to conventional ORA (based on marker genes) and GSDensity (based on cluster-specific gene sets). PSF identified a broader set of significant pathways with substantial overlap with both ORA and GSDensity, providing increased sensitivity due to its branch-level resolution. We further demonstrated that PSF-derived activity values can be used to detect spatially deregulated pathway branches, yielding results comparable to those obtained with spatially aware gene set analysis approaches such as GSDensity and spatialGE. The availability of pathway topology and branch-specific information also enabled the identification of potential intercellular communication via ligand-receptor interactions between deregulated pathways in adjacent tumor regions. To support interactive exploration of results, we developed the PSF Spatial Browser, an R Shiny application for visualizing pathway activities, gene expression patterns, and deregulated pathway networks.

Authors: Siras Hakobyan, Maria Schmidt, H. Binder, A. Arakelyan

Date Published: 14th Aug 2025

Publication Type: Journal

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

Data-driven discovery of chemical signatures for developing new inhibitors against human influenza viruses.

Abstract (Expand)

This study presents cheminformatics analysis of the antiviral chemical space targeting human influenza A and B viruses. By curating 407,366 small molecules from ChEMBL and PubChem, we evaluated … physicochemical properties, structural motifs, and activity trends across phenotypic and target-based assays. We found that 90.6% of evaluated molecules met Lipinski's Rule of Five, with active compounds exhibiting higher topological polar surface area and hydrogen bond donor groups. Target-specific analyses revealed distinct profiles for neuraminidase (NA) and hemagglutinin (HA) inhibitors, including larger molecular weights and increased rotatable bonds. Structural characterization identified cyclohexene, dihydropyran, and pyrimidine rings as prevalent in highly active molecules, while phthalimide motifs correlated with inactivity. Clustering of phenotypic assay data highlighted four promising and unique antiviral candidates, with unexplored chemical space. We also identified five multi-target scaffolds, including the curcumin-like scaffold, demonstrating dual inhibitory potential against two viral proteins. Molecular docking experiments on molecules within one of these multi-target scaffolds indicated their potential as initial hit candidates. Combined RMSD, PDF and DCCM analyses across molecular dynamics simulations elucidated the binding behaviour of five curcumin-like candidates. Two ligands remained as stable as the reference antivirals, one showed target-specific loss of affinity, and two dissociated rapidly, indicating that the stable pair should be prioritised for subsequent in vitro validation. Overall, the findings of this study can aid computer-aided drug design efforts, contributing to the development of novel antiviral agents against human influenza viruses.

Authors: Levon Kharatyan, Smbat Gevorgyan, Hamlet Khachatryan, Anastasiya Shavina, Astghik Hakobyan, Mher Matevosyan, Hovakim Zakaryan

Date Published: 5th Jun 2025

Publication Type: Journal

Telomere Maintenance Pathways in Lower-Grade Gliomas: Insights from Genetic Subtypes and Telomere Length Dynamics

Abstract (Expand)

Telomere maintenance mechanisms (TMMs) play a critical role in cancer biology, particularly in lower-grade gliomas (LGGs), where telomere dynamics and pathway activity remain poorly understood. In this … study, we analyzed TCGA-LGG and CGGA datasets, focusing on telomere length variations, pathway activity, and survival data across IDH subtypes. Additional validation was performed using the GEO COPD and GBM datasets, ensuring consistency in data processing and batch effect correction. Our analysis revealed significant differences in TEL pathway activation between Short- and Long-TL groups, emphasizing the central role of TERT in telomere maintenance. In contrast, ALT pathway activation displayed subtype-specific patterns, with IDH-wt tumors exhibiting the highest ALT activity, primarily driven by the RAD51 branch. Validation using CGGA data confirmed these findings, demonstrating consistent TEL and ALT pathway behaviors across datasets. Additionally, genetic subtype analysis revealed substantial telomere length variability associated with ATRX and IDH mutation status. Notably, IDHwt-ATRX WT tumors exhibited the shortest telomere length and the highest ALT pathway activity. These findings highlight distinct telomere regulatory dynamics across genetic subtypes of LGG and provide new insights into potential therapeutic strategies targeting telomere maintenance pathways.

Authors: Meline Hakobyan, Hans Binder, Arsen Arakelyan

Date Published: 28th Apr 2025

Publication Type: Journal

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