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Background Systems biology takes a holistic approach by handling biomolecules and their interactions as big systems. Network based approach has emerged as a natural way to model these systems with the idea of representing biomolecules as nodes and their interactions as edges. Very often the input data come from various sorts of omics analyses. Those resulting networks sometimes describe a wide range of aspects, for example different experiment conditions, species, tissue types, stimulating factors, mutants, or simply distinct interaction features of the same network produced by different algorithms. For these scenarios, synchronous visualization of more than one distinct network is an excellent mean to explore all the relevant networks efficiently. In addition, complementary analysis methods are needed and they should work in a workflow manner in order to gain maximal biological insights. Results In order to address the aforementioned needs, we have developed a Synchronous Network Data Integration (SyNDI) framework. This framework contains SyncVis, a Cytoscape application for user-friendly synchronous and simultaneous visualization of multiple biological networks, and it is seamlessly integrated with other bioinformatics tools via the Galaxy platform. We demonstrated the functionality and usability of the framework with three biological examples - we analyzed the distinct connectivity of plasma metabolites in networks associated with high or low latent cardiovascular disease risk; deeper insights were obtained from a few similar inflammatory response pathways in Staphylococcus aureus infection common to human and mouse; and regulatory motifs which have not been reported associated with transcriptional adaptations of Mycobacterium tuberculosis were identified. Conclusions Our SyNDI framework couples synchronous network visualization seamlessly with additional bioinformatics tools. The user can easily tailor the framework for his/her needs by adding new tools and datasets to the Galaxy platform. Electronic supplementary material The online version of this article (10.1186/s12859-018-2426-5) contains supplementary material, which is available to authorized users.

The emergence of systems biology necessitates development of platforms to organise and interpret plentitude of biological data. We present a system to integrate data across multiple bioinformatics databases and enable mining across various conceptual levels of biological information. The results are represented as complex networks. Context dependent mining of these networks is achieved by use of distances. Our approach is demonstrated with three applications: full metabolic network retrieval with network topology study, exploration of properties and relationships of a set of selected proteins, and combined visualisation and exploration of gene expression data with related pathways and ontologies.

We have developed a system called megNet for integrating and visualizing heterogeneous biological data in order to enable modeling biological phenomena using a systems approach. Herein we describe megNet, including a recently developed user interface for visualizing biological networks in three dimensions and a web user interface for taking input parameters from the user, and an in-house text mining system that utilizes an existing knowledge base. We demonstrate the software with a case study in which we integrate lipidomics data acquired in-house with interaction data from external databases, and then find novel interactions that could possibly explain our previous associations between biological data and medical images. The flexibility of megNet assures that the tool can be applied in diverse applications, from target discovery in medical applications to metabolic engineering in industrial biotechnology.

We have developed a system called megNet for integrating and visualizing heterogeneous biological data in order to enable modeling biological phenomena using a systems approach. Herein we describe megNet, including a recently developed user interface for visualizing biological networks in three dimensions and a web user interface for taking input parameters from the user, and an in-house text mining system that utilizes an existing knowledge base. We demonstrate the software with a case study in which we integrate lipidomics data acquired in-house with interaction data from external databases, and then find novel interactions that could possibly explain our previous associations between biological data and medical images. The flexibility of megNet assures that the tool can be applied in diverse applications, from target discovery in medical applications to metabolic engineering in industrial biotechnology.

Recent clinical evidence suggests important role of lipid and amino acid metabolism in early pre-autoimmune stages of type 1 diabetes pathogenesis. We study the molecular paths associated with the incidence of insulitis and type 1 diabetes in the Non-Obese Diabetic (NOD) mouse model using available gene expression data from the pancreatic tissue from young pre-diabetic mice. We apply a graph-theoretic approach by using a modified color coding algorithm to detect optimal molecular paths associated with specific phenotypes in an integrated biological network encompassing heterogeneous interaction data types. In agreement with our recent clinical findings, we identified a path downregulated in early insulitis involving dihydroxyacetone phosphate acyltransferase (DHAPAT), a key regulator of ether phospholipid synthesis. The pathway involving serine/threonine-protein phosphatase (PP2A), an upstream regulator of lipid metabolism and insulin secretion, was found upregulated in early insulitis. Our findings provide further evidence for an important role of lipid metabolism in early stages of type 1 diabetes pathogenesis, as well as suggest that such dysregulation of lipids and related increased oxidative stress can be tracked to beta cells.

In response to environmental challenges, biological systems respond with dynamic adaptive changes in order to maintain the functionality of the system. Such adaptations may lead to cumulative stress over time, possibly leading to global failure of the system. When studying such systems responses, it is therefore important to understand them in system-wide and dynamic context. Here we hypothesize that dynamic changes in the topology of functional modules of integrated biological networks reflect their activity under specific environmental challenges. We introduce topological enrichment analysis of functional subnetworks (TEAFS), a method for the analysis of integrated molecular profile and interactome data, which we validated by comprehensive metabolomic analysis of dynamic yeast response under oxidative stress. TEAFS identified activation of multiple stress response related mechanisms, such as lipid metabolism and phospholipid biosynthesis. We identified, among others, a fatty acid elongase IFA38 as a hub protein which was absent at all time points under oxidative stress conditions. The deletion mutant of the IFA38 encoding gene is known for the accumulation of ceramides. By applying a comprehensive metabolomic analysis, we confirmed the increased concentrations over time of ceramides and palmitic acid, a precursor of de novoceramide biosynthesis. Our results imply that the connectivity of the system is being dynamically modulated in response to oxidative stress, progressively leading to the accumulation of (lipo)toxic lipids such as ceramides. Studies of local network topology dynamics can be used to investigate as well as predict the activity of biological processes and the system’s responses to environmental challenges and interventions.

Background: Saccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions. Previously, oxygen-dependent phenotypes have been studied individually at the transcriptional, metabolite, and flux level. However, the regulation of cell phenotype occurs across the different levels of cell function. Integrative analysis of data from multiple levels of cell function in the context of a network of several known biochemical interaction types could enable identification of active regulatory paths not limited to a single level of cell function.Results: The graph theoretical method called Enriched Molecular Path detection (EMPath) was extended to enable integrative utilization of transcription and flux data. The utility of the method was demonstrated by detecting paths associated with phenotype differences of S. cerevisiae under three different conditions of oxygen provision: 20.9%, 2.8% and 0.5%. The detection of molecular paths was performed in an integrated genome-scale metabolic and protein-protein interaction network.Conclusions: The molecular paths associated with the phenotype differences of S. cerevisiae under conditions of different oxygen provisions revealed paths of molecular interactions that could potentially mediate information transfer between processes that respond to the particular oxygen availabilities.

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes., Author Summary We have recently found that distinct metabolic disturbances precede β-cell autoimmunity in children who later progress to type 1 diabetes (T1D). Here we performed a murine study using non-obese diabetic (NOD) mice that recapitulated the protocol used in human, followed up by independent studies where NOD mice were studied in relation to risk of diabetes progression. We found that young female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum subgroup. The metabolic phenotypes observed in our study could be relevant as end points for studies investigating T1D pathogenesis and/or responses to interventions. By proceeding from a clinical study via metabolomics and modeling to an experimental model using a similar study design, then evolving further to tissue-specific studies, we hereby also present a conceptually novel approach to reversed translation that may be useful in future therapeutic studies in the context of prevention and treatment of T1D as well as of other diseases characterized by long prodromal periods.

Motivation: Integration of heterogeneous data in life sciences is a growing and recognized challenge. The problem is not only to enable the study of such data within the context of a biological question but also more fundamentally, how to represent the available knowledge and make it accessible for mining.Results: Our integration approach is based on the premise that relationships between biological entities can be represented as a complex network. The context dependency is achieved by a judicious use of distance measures on these networks. The biological entities and the distances between them are mapped for the purpose of visualization into the lower dimensional space using the Sammon's mapping. The system implementation is based on a multi-tier architecture using a native XML database and a software tool for querying and visualizing complex biological networks. The functionality of our system is demonstrated with two examples: (1) A multiple pathway retrieval, in which, given a pathway name, the system finds all the relationships related to the query by checking available metabolic pathway, transcriptional, signaling, protein–protein interaction and ontology annotation resources and (2) A protein neighborhood search, in which given a protein name, the system finds all its connected entities within a specified depth. These two examples show that our system is able to conceptually traverse different databases to produce testable hypotheses and lead towards answers to complex biological questions.