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93 Publications visible to you, out of a total of 93
Machine learned-based visualization of the diversity of grapevine genomes worldwide and in Armenia using SOMmelier

Abstract (Expand)

In the proposed study three major issues have been addressed: Firstly, the diversity of grapevine accessions worldwide and particularly in Armenia, a small country located in the largely volcanic … Armenian Highlands, is incredibly rich in cultivated and especially wild grapes; secondly, the information hidden in their (whole) genomes, e.g., about the domestication history of grapevine over the last 11,000 years and phenotypic traits such as cultivar utilization and a putative resistance against powdery mildew, and, thirdly machine learning methods to extract and to visualize this information in an easy to percept way. We shortly describe the Self Origanizing Maps (SOM) portrayal method called “SOMmelier” (as the vine-genome “waiter”) and illustrate its power by applying it to whole genome data of hundreds of grapevine accessions. We also give a short outlook on possible future directions of machine learning in grapevine transcriptomics and ampelogaphy.

Authors: Kristina Magaryan, Maria Nikogհosyan, Anush Baloyan, Hripsime Gasoyan, Emma Hovhannisyan, Levon Galstyan, Tomas Konecny, Arsen Arakelyan, Hans Binder

Date Published: 6th Dec 2023

Publication Type: Journal

PSF toolkit: an R package for pathway curation and topology-aware analysis.

Abstract (Expand)

Most high throughput genomic data analysis pipelines currently rely on over-representation or gene set enrichment analysis (ORA/GSEA) approaches for functional analysis. In contrast, topology-based … pathway analysis methods, which offer a more biologically informed perspective by incorporating interaction and topology information, have remained underutilized and inaccessible due to various limiting factors. These methods heavily rely on the quality of pathway topologies and often utilize predefined topologies from databases without assessing their correctness. To address these issues and make topology-aware pathway analysis more accessible and flexible, we introduce the PSF (Pathway Signal Flow) toolkit R package. Our toolkit integrates pathway curation and topology-based analysis, providing interactive and command-line tools that facilitate pathway importation, correction, and modification from diverse sources. This enables users to perform topology-based pathway signal flow analysis in both interactive and command-line modes. To showcase the toolkit's usability, we curated 36 KEGG signaling pathways and conducted several use-case studies, comparing our method with ORA and the topology-based signaling pathway impact analysis (SPIA) method. The results demonstrate that the algorithm can effectively identify ORA enriched pathways while providing more detailed branch-level information. Moreover, in contrast to the SPIA method, it offers the advantage of being cut-off free and less susceptible to the variability caused by selection thresholds. By combining pathway curation and topology-based analysis, the PSF toolkit enhances the quality, flexibility, and accessibility of topology-aware pathway analysis. Researchers can now easily import pathways from various sources, correct and modify them as needed, and perform detailed topology-based pathway signal flow analysis. In summary, our PSF toolkit offers an integrated solution that addresses the limitations of current topology-based pathway analysis methods. By providing interactive and command-line tools for pathway curation and topology-based analysis, we empower researchers to conduct comprehensive pathway analyses across a wide range of applications.

Authors: S. Hakobyan, A. Stepanyan, L. Nersisyan, H. Binder, A. Arakelyan

Date Published: 8th Sep 2023

Publication Type: Journal

PSF toolkit: an R package for pathway curation and topology-aware analysis

Abstract (Expand)

Most high throughput genomic data analysis pipelines currently rely on over-representation or gene set enrichment analysis (ORA/GSEA) approaches for functional analysis. In contrast, topology-based … pathway analysis methods, which offer a more biologically informed perspective by incorporating interaction and topology information, have remained underutilized and inaccessible due to various limiting factors. These methods heavily rely on the quality of pathway topologies and often utilize predefined topologies from databases without assessing their correctness. To address these issues and make topology-aware pathway analysis more accessible and flexible, we introduce the PSF (Pathway Signal Flow) toolkit R package. Our toolkit integrates pathway curation and topology-based analysis, providing interactive and command-line tools that facilitate pathway importation, correction, and modification from diverse sources. This enables users to perform topology-based pathway signal flow analysis in both interactive and command-line modes. To showcase the toolkit’s usability, we curated 36 KEGG signaling pathways and conducted several use-case studies, comparing our method with ORA and the topology-based signaling pathway impact analysis (SPIA) method. The results demonstrate that the algorithm can effectively identify ORA enriched pathways while providing more detailed branch-level information. Moreover, in contrast to the SPIA method, it offers the advantage of being cut-off free and less susceptible to the variability caused by selection thresholds. By combining pathway curation and topology-based analysis, the PSF toolkit enhances the quality, flexibility, and accessibility of topology-aware pathway analysis. Researchers can now easily import pathways from various sources, correct and modify them as needed, and perform detailed topology-based pathway signal flow analysis. In summary, our PSF toolkit offers an integrated solution that addresses the limitations of current topology-based pathway analysis methods. By providing interactive and command-line tools for pathway curation and topology-based analysis, we empower researchers to conduct comprehensive pathway analyses across a wide range of applications.

Authors: Siras Hakobyan, Ani Stepanyan, Lilit Nersisyan, Hans Binder, Arsen Arakelyan

Date Published: 23rd Aug 2023

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

Transcriptomic Maps of Colorectal Liver Metastasis: Machine Learning of Gene Activation Patterns and Epigenetic Trajectories in Support of Precision Medicine.

Abstract (Expand)

The molecular mechanisms of the liver metastasis of colorectal cancer (CRLM) remain poorly understood. Here, we applied machine learning and bioinformatics trajectory inference to analyze a gene … expression dataset of CRLM. We studied the co-regulation patterns at the gene level, the potential paths of tumor development, their functional context, and their prognostic relevance. Our analysis confirmed the subtyping of five liver metastasis subtypes (LMS). We provide gene-marker signatures for each LMS, and a comprehensive functional characterization that considers both the hallmarks of cancer and the tumor microenvironment. The ordering of CRLMs along a pseudotime-tree revealed a continuous shift in expression programs, suggesting a developmental relationship between the subtypes. Notably, trajectory inference and personalized analysis discovered a range of epigenetic states that shape and guide metastasis progression. By constructing prognostic maps that divided the expression landscape into regions associated with favorable and unfavorable prognoses, we derived a prognostic expression score. This was associated with critical processes such as epithelial-mesenchymal transition, treatment resistance, and immune evasion. These factors were associated with responses to neoadjuvant treatment and the formation of an immuno-suppressive, mesenchymal state. Our machine learning-based molecular profiling provides an in-depth characterization of CRLM heterogeneity with possible implications for treatment and personalized diagnostics.

Authors: O. Ashekyan, N. Shahbazyan, Y. Bareghamyan, A. Kudryavzeva, D. Mandel, M. Schmidt, H. Loeffler-Wirth, M. Uduman, D. Chand, D. Underwood, G. Armen, A. Arakelyan, L. Nersisyan, H. Binder

Date Published: 28th Jul 2023

Publication Type: Journal

Generation of three induced pluripotent stem cell lines (RAUi001-A, RAUi001-B and RAUi001-C) from peripheral blood mononuclear cells of a healthy Armenian individual.

Abstract (Expand)

The study of pathological processes in cells carrying mutations should be carried out in comparison with a healthy control group. Familial Mediterranean fever (FMF), which is caused by a mutation in … the MEFV gene, is predominantly found in people of Armenian nationality with the prevalence of 14–100 per 10000. We have obtained induced pluripotent stem cells (iPSCs) from Armenian healthy patient, which will be included as a control group in the study of this disease. iPSCs rapidly proliferate in colonies of cells with a typical pluripotent-like morphology, have a normal karyotype (46,XX). iPSCs express pluripotency markers (OCT4, SOX2, TRA-1–60, NANOG) and are able to give derivatives of three germ layers.

Authors: Elena V. Grigor’eva, Anastasia A. Malakhova, Lilit Ghukasyan, Varduhi Hayrapetyan, Sofi Atshemyan, Valentina Vardanyan, Suren M. Zakian, Roksana Zakharyan, Arsen Arakelyan

Date Published: 17th Jun 2023

Publication Type: Journal

Atlas of mRNA translation and decay for bacteria.

Abstract (Expand)

Regulation of messenger RNA stability is pivotal for programmed gene expression in bacteria and is achieved by a myriad of molecular mechanisms. By bulk sequencing of 5' monophosphorylated mRNA … decay intermediates (5'P), we show that cotranslational mRNA degradation is conserved among both Gram-positive and -negative bacteria. We demonstrate that, in species with 5'-3' exonucleases, the exoribonuclease RNase J tracks the trailing ribosome to produce an in vivo single-nucleotide toeprint of the 5' position of the ribosome. In other species lacking 5'-3' exonucleases, ribosome positioning alters endonucleolytic cleavage sites. Using our metadegradome (5'P degradome) sequencing approach, we characterize 5'P mRNA decay intermediates in 96 species including Bacillus subtilis, Escherichia coli, Synechocystis spp. and Prevotella copri and identify codon- and gene-level ribosome stalling responses to stress and drug treatment. We also apply 5'P sequencing to complex clinical and environmental microbiomes and demonstrate that metadegradome sequencing provides fast, species-specific posttranscriptional characterization of responses to drug or environmental perturbations. Finally we produce a degradome atlas for 96 species to enable analysis of mechanisms of RNA degradation in bacteria. Our work paves the way for the application of metadegradome sequencing to investigation of posttranscriptional regulation in unculturable species and complex microbial communities.

Authors: S. Huch, L. Nersisyan, M. Ropat, D. Barrett, M. Wu, J. Wang, V. D. Valeriano, N. Vardazaryan, J. Huerta-Cepas, W. Wei, J. Du, L. M. Steinmetz, L. Engstrand, V. Pelechano

Date Published: 5th Jun 2023

Publication Type: Journal

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