Biology subjects

Kuperstein, I.

Publications and source records attributed to Kuperstein, I..

5 recordsLinked to original sources

bioRxiv2018

The Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease

A multitude of factors contribute to complex diseases and can be measured with \"omics\" methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, http://vmh.life) database encapsulating current knowledge of human metabolism within five interlinked resources \"Human metabolism\", \"Gut microbiome\", \"Disease\", \"Nutrition\", and \"ReconMaps\". The VMH captures 5,180 unique metabolites, 17,730 unique reactions, 3,288 human genes, 255 Mendelian diseases, 818 microbes, 632,685 microbial genes, and 8,790 food items. The VMHs unique features are i) the hosting the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; ii) seven human metabolic maps for data visualization; iii) a nutrition designer; iv) a user-friendly webpage and application-programming interface to access its content; and v) user feedback option for community engagement. We demonstrate with four examples the VMHs utility. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community.

systems biology↗

bioRxiv2018

Metabolic and signalling network map integration: application to cross-talk studies and omics data analysis in cancer

BackgroundThe interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have never been integrated together. We aim at filling in this gap by creating an integrated resource of both signalling and metabolic pathways allowing a visual exploration of multi-level omics data and study of cross-regulatory circuits between these processes in health and in disease.\n\nResultsWe combined two comprehensive manually curated network maps. Atlas of Cancer Signalling Network (ACSN), containing mechanisms frequently implicated in cancer; and ReconMap 2.0, a comprehensive reconstruction of human metabolic network. We linked ACSN and ReconMap 2.0 maps via common players and represented the two maps as interconnected layers using the NaviCell platform for maps exploration. In addition, proteins catalysing metabolic reactions in ReconMap 2.0 were not previously visually represented on the map canvas. This precluded visualisation of omics data in the context of ReconMap 2.0. We suggested a solution for displaying protein nodes on the ReconMap 2.0 map in the vicinity of the corresponding reaction or process nodes. This permits multi-omics data visualisation in the context of both map layers. Exploration and shuttling between the two map layers is possible using Google Maps-like features of NaviCell. The integrated ACSN-ReconMap 2.0 resource is accessible online and allows data visualisation through various modes such as markers, heat maps, bar-plots, glyphs and map staining. The integrated resource was applied for comparison of immunoreactive and proliferative ovarian cancer subtypes using transcriptomic, copy number and mutation multi-omics data. A certain number of metabolic and signalling processes specifically deregulated in each of the ovarian cancer sub-types were identified.\n\nConclusionsAs knowledge evolves and new omics data becomes more heterogeneous, gathering together existing domains of biology under common platforms is essential. We believe that an integrated ACSN-ReconMap 2.0 resource will help in understanding various disease mechanisms and discovery of new interactions at the intersection of cell signalling and metabolism. In addition, the successful integration of metabolic and signalling networks allows broader systems biology approach application for data interpretation and retrieval of intervention points to tackle simultaneously the key players coordinating signalling and metabolism in human diseases.

systems biology↗

bioRxiv2017

Application of Atlas of Cancer Signalling Network in pre-clinical studies

Initiation and progression of cancer involve multiple molecular mechanisms. The knowledge on these mechanisms is expanding and should be converted into guidelines for tackling the disease. We discuss here formalization of biological knowledge into a comprehensive resource Atlas of Cancer Signalling Network (ACSN) and Google Maps-based tool NaviCell that supports map navigation. The application of maps for omics data visualisation in the context of signalling maps is possible using NaviCell Web Service module and NaviCom tool for generation of network-based molecular portraits of cancer using multi-level omics data. We review how these resources and tools are applied for cancer pre-clinical studies among others for rationalizing synergistic effect of drugs and designing complex disease stage-specific druggable interventions following structural analysis of the maps together with omics data. Modules and maps of ACSN as signatures of biological functions, can help in cancer data analysis and interpretation. In addition, they can also be used to find association between perturbations in particular molecular mechanisms to the risk of a specific cancer type development. These approaches and beyond help to study interplay between molecular mechanisms of cancer, deciphering how gene interactions govern hallmarks of cancer in specific context. We discuss a perspective to develop a flexible methodology and a pipeline to enable systematic omics data analysis in the context of signalling network maps, for stratifying patients and suggesting interventions points and drug repositioning in cancer and other human diseases.

systems biology↗

bioRxiv2016

Knowledge Formalization and High-Throughput Data Visualization Using Signaling Network Maps

Generation and usage of high-quality molecular signalling network maps can be augmented by standardising notations, establishing curation workflows and application of computational biology methods to exploit the knowledge contained in the maps. In this manuscript, we summarize the major aims and challenges of assembling information in the form of comprehensive maps of molecular interactions. Mainly, we share our experience gained while creating the Atlas of Cancer Signalling Network. In the step-by-step procedure, we describe the map construction process and suggest solutions for map complexity management by introducing a hierarchical modular map structure. In addition, we describe the NaviCell platform, a computational technology using Google Maps API to explore comprehensive molecular maps similar to geographical maps, and explain the advantages of semantic zooming principles for map navigation. We also provide the outline to prepare signalling network maps for navigation using the NaviCell platform. Finally, several examples of cancer high-throughput data analysis and visualization in the context of comprehensive signalling maps are presented.

systems biology↗

bioRxiv2016

NaviCom: A web application to create interactive molecular network portraits using multi-level omics data

Human diseases such as cancer are routinely characterized by high-throughput molecular technologies, and multi-level omics data are accumulated in public databases at increasing rate. Retrieval and visualization of these data in the context of molecular network maps can provide insights into the pattern of molecular functions encompassed by an omics profile. In order to make this task easy, we developed NaviCom, a Python package and web platform for visualization of multi-level omics data on top of biological network maps. NaviCom is bridging the gap between cBioPortal, the most used resource of large-scale cancer omics data and NaviCell, a data visualization web service that contains several molecular network map collections. NaviCom proposes several standardized modes of data display on top of molecular network maps, allowing to address specific biological questions. We illustrate how users can easily create interactive network-based cancer molecular portraits via NaviCom web interface using the maps of Atlas of Cancer Signaling Network (ACSN) and other maps. Analysis of these molecular portraits can help in formulating a scientific hypothesis on the molecular mechanisms deregulated in the studied disease.

systems biology↗