Lost in translation: data integration tools meet the Semantic Web (experiences from the Ondex project)

More information is now being published in machine processable form on the web and, as de-facto distributed knowledge bases are materializing, partly encouraged by the vision of the Semantic Web, the focus is shifting from the publication of this information to its consumption. Platforms for data integration, visualization and analysis that are based on a graph representation of information appear first candidates to be consumers of web-based information that is readily expressible as graphs. The question is whether the adoption of these platforms to information available on the Semantic Web requires some adaptation of their data structures and semantics. Ondex is a network-based data integration, analysis and visualization platform which has been developed in a Life Sciences context. A number of features, including semantic annotation via ontologies and an attention to provenance and evidence, make this an ideal candidate to consume Semantic Web information, as well as a prototype for the application of network analysis tools in this context. By analyzing the Ondex data structure and its usage, we have found a set of discrepancies and errors arising from the semantic mismatch between a procedural approach to network analysis and the implications of a web-based representation of information. We report in the paper on the simple methodology that we have adopted to conduct such analysis, and on issues that we have found which may be relevant for a range of similar platformsComment: Presented at DEIT, Data Engineering and Internet Technology, 2011 IEEE: CFP1113L-CD

LAITOR - Literature Assistant for Identification of Terms co-Occurrences and Relationships

BACKGROUND: Biological knowledge is represented in scientific literature that often describes the function of genes/proteins (bioentities) in terms of their interactions (biointeractions). Such bioentities are often related to biological concepts of interest that are specific of a determined research field. Therefore, the study of the current literature about a selected topic deposited in public databases, facilitates the generation of novel hypotheses associating a set of bioentities to a common context. RESULTS: We created a text mining system (LAITOR: Literature Assistant for Identification of Terms co-Occurrences and Relationships) that analyses co-occurrences of bioentities, biointeractions, and other biological terms in MEDLINE abstracts. The method accounts for the position of the co-occurring terms within sentences or abstracts. The system detected abstracts mentioning protein-protein interactions in a standard test (BioCreative II IAS test data) with a precision of 0.82-0.89 and a recall of 0.48-0.70. We illustrate the application of LAITOR to the detection of plant response genes in a dataset of 1000 abstracts relevant to the topic. CONCLUSIONS: Text mining tools combining the extraction of interacting bioentities and biological concepts with network displays can be helpful in developing reasonable hypotheses in different scientific backgrounds

A Guide to Conquer the Biological Network Era Using Graph Theory

Networks are one of the most common ways to represent biological systems as complex sets of binary interactions or relations between different bioentities. In this article, we discuss the basic graph theory concepts and the various graph types, as well as the available data structures for storing and reading graphs. In addition, we describe several network properties and we highlight some of the widely used network topological features. We briefly mention the network patterns, motifs and models, and we further comment on the types of biological and biomedical networks along with their corresponding computer- and human-readable file formats. Finally, we discuss a variety of algorithms and metrics for network analyses regarding graph drawing, clustering, visualization, link prediction, perturbation, and network alignment as well as the current state-of-the-art tools. We expect this review to reach a very broad spectrum of readers varying from experts to beginners while encouraging them to enhance the field further. © Copyright © 2020 Koutrouli, Karatzas, Paez-Espino and Pavlopoulos

Deforming the Starobinsky model in ghost-free higher derivative supergravities

We consider higher derivative supergravities that are dual to ghost-free N=1 supergravity theories in the Einstein frame. The duality is implemented by deforming the Kähler function, and/or the superpotential, to include nonlinear dependences on chiral fields that, in other approaches, play the role of the Lagrange multipliers employed to establish this duality. These models are of the no-scale type, and in the minimal case, they require the presence of four chiral multiplets, with a Kähler potential having the structure of the SU(4,1)/SU(4)×U(1) coset manifold. In the standard N=1 supergravity formulation, these models are described by a multifield scalar potential, featuring Starobinsky-like behavior in particular directions. © 2017 American Physical Society

Network analysis of genes and their association with diseases

A plethora of network-based approaches within the Systems Biology universe have been applied, to date, to investigate the underlying molecular mechanisms of various human diseases. In the present study, we perform a bipartite, topological and clustering graph analysis in order to gain a better understanding of the relationships between human genetic diseases and the relationships between the genes that are implicated in them. For this purpose, disease-disease and gene-gene networks were constructed from combined gene-disease association networks. The latter, were created by collecting and integrating data from three diverse resources, each one with different content covering from rare monogenic disorders to common complex diseases. This data pluralism enabled us to uncover important associations between diseases with unrelated phenotypic manifestations but with common genetic origin. For our analysis, the topological attributes and the functional implications of the individual networks were taken into account and are shortly discussed. We believe that some observations of this study could advance our understanding regarding the etiology of a disease with distinct pathological manifestations, and simultaneously provide the springboard for the development of preventive and therapeutic strategies and its underlying genetic mechanisms. © 2016 Elsevier B.V

Data and programs in support of network analysis of genes and their association with diseases

The network-based approaches that were employed in order to depict the relationships between human genetic diseases and their associated genes are described. Towards this direction, monopartite disease-disease and gene-gene networks were constructed from bipartite gene-disease association networks. The latter were created by collecting and integrating data from three diverse resources, each one with different content, covering from rare monogenic disorders to common complex diseases. Moreover, topological and clustering graph analyses were performed. The methodology and the programs presented in this article are related to the research article entitled “Network analysis of genes and their association with diseases” [1]. © 2016 The Author

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach

Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient. © 2022, The Author(s), under exclusive licence to Springer Nature Limited

Flame: A web tool for functional and literature enrichment analysis of multiple gene lists

Functional enrichment is a widely used method for interpreting experimental results by identifying classes of proteins/genes associated with certain biological functions, pathways, diseases, or phenotypes. Despite the variety of existing tools, most of them can process a single list per time, thus making a more combinatorial analysis more complicated and prone to errors. In this article, we present FLAME, a web tool for combining multiple lists prior to enrichment analysis. Users can upload several lists and use interactive UpSet plots, as an alternative to Venn diagrams, to handle unions or intersections among the given input files. Functional and literature enrichment, along with gene conversions, are offered by g:Profiler and aGOtool applications for 197 organisms. FLAME can analyze genes/proteins for related articles, Gene Ontologies, pathways, annotations, regulatory motifs, domains, diseases, and phenotypes, and can also generate protein–protein interactions derived from STRING. We have validated FLAME by interrogating gene expression data associated with the sensitivity of the distal part of the large intestine to experimental colitis-propelled colon cancer. FLAME comes with an interactive user-friendly interface for easy list manipulation and exploration, while results can be visualized as interactive and parameterizable heatmaps, barcharts, Manhattan plots, networks, and tables. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Bipartite graphs in systems biology and medicine: A survey of methods and applications

The latest advances in high-throughput techniques during the past decade allowed the systems biology field to expand significantly. Today, the focus of biologists has shifted from the study of individual biological components to the study of complex biological systems and their dynamics at a larger scale. Through the discovery of novel bioentity relationships, researchers reveal new information about biological functions and processes. Graphs are widely used to represent bioentities such as proteins, genes, small molecules, ligands, and others such as nodes and their connections as edges within a network. In this review, special focus is given to the usability of bipartite graphs and their impact on the field of network biology and medicine. Furthermore, their topological properties and how these can be applied to certain biological case studies are discussed. Finally, available methodologies and software are presented, and useful insights on how bipartite graphs can shape the path toward the solution of challenging biological problems are provided. © The Author(s) 2018

Inflation in R2 supergravity with non-minimal superpotentials

We investigate the cosmological inflation in a class of supergravity models that are generalizations of non-supersymmetric R2 models. Although such models have been extensively studied recently, especially after the launch of the PLANCK and BICEP2 data, the class of models that can be constructed has not been exhausted. In this note, working in a supergravity model that is a generalization of Cecotti's model, we show that the appearance of new superpotential terms, which are quadratic in the superfield Λ that couples to the Ricci supermultiplet, alters substantially the form of the scalar potential. The arising potential has the form of the Starobinsky potential times a factor that is exponential in the inflaton field and dominates for large inflaton values. We show that the well-known Starobinsky inflation scenario is maintained only for unnaturally small fine-tuned values of the coupling describing the Λ2 superpotential terms. A welcome feature is the possible increase of the tensor to scalar ratio r, within the limits set by the new Planck and BICEP2 data. © 2015 The Authors