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12 Publications visible to you, out of a total of 12
oposSOM-Browser: an interactive tool to explore omics data landscapes in health science.

Abstract (Expand)

Background: oposSOM is a comprehensive, machine learning based open-source data analysis software combining functionalities such as diversity analyses, biomarker selection, function mining, and … visualization. Results: These functionalities are now available as interactive web-browser application for a broader user audience interested in extracting detailed information from high-throughput omics data sets pre-processed by oposSOM. It enables interactive browsing of single-gene and gene set profiles, of molecular 'portrait landscapes', of associated phenotype diversity, and signalling pathway activation patterns. Conclusion: The oposSOM-Browser makes available interactive data browsing for five transcriptome data sets of cancer (melanomas, B-cell lymphomas, gliomas) and of peripheral blood (sepsis and healthy individuals) at www.izbi.uni-leipzig.de/opossom-browser . Keywords: Interactive data analysis; Results browser; Transcriptomics.

Authors: Henry Loeffler-Wirth, Jasmin Reikowski, Siras Hakobyan, Jonas Wagner, Hans Binder

Date Published: 19th Oct 2020

Publication Type: Journal

SOMmelier-Intuitive Visualization of the Topology of Grapevine Genome Landscapes Using Artificial Neural Networks.

Abstract (Expand)

BACKGROUND: Whole-genome studies of vine cultivars have brought novel knowledge about the diversity, geographical relatedness, historical origin and dissemination, phenotype associations and genetic … markers. METHOD: We applied SOM (self-organizing maps) portrayal, a neural network-based machine learning method, to re-analyze the genome-wide Single Nucleotide Polymorphism (SNP) data of nearly eight hundred grapevine cultivars. The method generates genome-specific data landscapes. Their topology reflects the geographical distribution of cultivars, indicates paths of cultivar dissemination in history and genome-phenotype associations about grape utilization. RESULTS: The landscape of vine genomes resembles the geographic map of the Mediterranean world, reflecting two major dissemination paths from South Caucasus along a northern route via Balkan towards Western Europe and along a southern route via Palestine and Maghreb towards Iberian Peninsula. The Mediterranean and Black Sea, as well as the Pyrenees, constitute barriers for genetic exchange. On the coarsest level of stratification, cultivars divide into three major groups: Western Europe and Italian grapes, Iberian grapes and vine cultivars from Near East and Maghreb regions. Genetic landmarks were associated with agronomic traits, referring to their utilization as table and wine grapes. Pseudotime analysis describes the dissemination of grapevines in an East to West direction in different waves of cultivation. CONCLUSION: In analogy to the tasks of the wine waiter in gastronomy, the sommelier, our 'SOMmelier'-approach supports understanding the diversity of grapevine genomes in the context of their geographic and historical background, using SOM portrayal. It offers an option to supplement vine cultivar passports by genome fingerprint portraits.

Authors: M. Nikoghosyan, M. Schmidt, K. Margaryan, H. Loeffler-Wirth, A. Arakelyan, H. Binder

Date Published: 17th Jul 2020

Publication Type: Journal

Transcriptome-Guided Drug Repositioning.

Abstract (Expand)

Drug repositioning can save considerable time and resources and significantly speed up the drug development process. The increasing availability of drug action and disease-associated transcriptome data … makes it an attractive source for repositioning studies. Here, we have developed a transcriptome-guided approach for drug/biologics repositioning based on multi-layer self-organizing maps (ml-SOM). It allows for analyzing multiple transcriptome datasets by segmenting them into layers of drug action- and disease-associated transcriptome data. A comparison of expression changes in clusters of functionally related genes across the layers identifies "drug target" spots in disease layers and evaluates the repositioning possibility of a drug. The repositioning potential for two approved biologics drugs (infliximab and brodalumab) confirmed the drugs' action for approved diseases (ulcerative colitis and Crohn's disease for infliximab and psoriasis for brodalumab). We showed the potential efficacy of infliximab for the treatment of sarcoidosis, but not chronic obstructive pulmonary disease (COPD). Brodalumab failed to affect dysregulated functional gene clusters in Crohn's disease (CD) and systemic juvenile idiopathic arthritis (SJIA), clearly indicating that it may not be effective in the treatment of these diseases. In conclusion, ml-SOM offers a novel approach for transcriptome-guided drug repositioning that could be particularly useful for biologics drugs.

Authors: A. Arakelyan, L. Nersisyan, M. Nikoghosyan, S. Hakobyan, A. Simonyan, L. Hopp, H. Loeffler-Wirth, H. Binder

Date Published: 12th Dec 2019

Publication Type: Journal

Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers.

Abstract (Expand)

We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all … enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2. As another mechanism, we studied the coupling between the energy metabolism and epigenetics via metabolites that act as cofactors of JmjC-type demethylases. Our study results suggest that Burkitt's lymphoma and diffuse large B-cell Lymphoma differ by an imbalance of repressive and poised promoters, which is governed predominantly by the activity of methyltransferases and the underrepresentation of demethylases in this regulation. The data further suggest that coupling of epigenetics with the energy metabolism can also be an important factor in lymphomagenesis in the absence of direct mutations of genes in metabolic pathways. Understanding of epigenetic deregulation in lymphoma and possibly in cancers in general must go beyond simple schemes using only a few modes of regulation.

Authors: Lydia Hopp, Lilit Nersisyan, Henry Löffler-Wirth, Arsen Arakelyan, Hans Binder

Date Published: 21st Oct 2015

Publication Type: Journal

A topological map of the genetic components of grapevine-Admixture meets SOMmelier machine learning

Abstract (Expand)

Inferring the genetic structure of populations at the subpopulation level is crucial for understanding the evolutionary forces and demographic histories that shape genetic diversity. Among the most … widely used approaches in population genetics are methods based on admixture and structure modeling—named after the respective software tools—which have become standard due to their intuitive, interpretable outputs. In this study, we address a key methodological question: how does traditional admixture-based decomposition of genetic components in multilocus population data relate to clustering approaches that leverage machine learning, specifically Self-Organizing Maps (SOMs)? We implemented this approach through our custom SOM-based tool, SOMmelier, which enables the portrayal of genetic structure by identifying modules of co-mutated SNPs and arranging them in a topology-aware genetic landscape. In this context, topology-awareness refers to the organization of genetic modules in a two-dimensional map, where their spatial proximity reflects mutual similarity. As a case study, we applied SOMmelier to investigate the population genetics of European grapevine. Based on prior literature, we considered up to six genetic components, which formed a genetic landscape that closely mirrors the geographic expanse of the classical Mediterranean world—from Western Asia through the Caucasus to Western Europe. The resulting topology reflects the dynamic spatial and temporal nature of grapevine domestication and diffusion. SOMmelier thus represents a complementary and powerful framework for genetic data analysis. By integrating the topological structure of SNP co-variation, it offers new perspectives on population structure, evolutionary history, and trait associations in grapevine—and has broader applicability to other species and systems in population genetics.

Author: Anush Baloyan, Tomas Konecny, Emma Hovhannisyan, Nate Zadirako, Maria Nikoghosyan, Hans Binder

Date Published: No date defined

Publication Type: Journal

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