OmicsNet: a web-based tool for creation and visual analysis of biological networks in 3D space

Abstract Biological networks play increasingly important roles in omics data integration and systems biology. Over the past decade, many excellent tools have been developed to support creation, analysis and visualization of biological networks. However, important limitations remain: most tools are standalone programs, the majority of them focus on protein-protein interaction (PPI) or metabolic networks, and visualizations often suffer from ‘hairball’ effects when networks become large. To help address these limitations, we developed OmicsNet - a novel web-based tool that allows users to easily create different types of molecular interaction networks and visually explore them in a three-dimensional (3D) space. Users can upload one or multiple lists of molecules of interest (genes/proteins, microRNAs, transcription factors or metabolites) to create and merge different types of biological networks. The 3D network visualization system was implemented using the powerful Web Graphics Library (WebGL) technology that works natively in most major browsers. OmicsNet supports force-directed layout, multi-layered perspective layout, as well as spherical layout to help visualize and navigate complex networks. A rich set of functions have been implemented to allow users to perform coloring, shading, topology analysis, and enrichment analysis. OmicsNet is freely available at http://www.omicsnet.ca.

[1]  David J. Arenillas,et al.  JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework , 2017, Nucleic acids research.

[2]  Artemis G. Hatzigeorgiou,et al.  DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA–gene interactions , 2017, Nucleic Acids Res..

[3]  M. Ritchie,et al.  Methods of integrating data to uncover genotype–phenotype interactions , 2015, Nature Reviews Genetics.

[4]  Hsien-Da Huang,et al.  miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions , 2017, Nucleic Acids Res..

[5]  N. Schork.  Personalized medicine: Time for one-person trials , 2015, Nature.

[6]  Rick M. Maizels,et al.  Immune Regulation by helminth parasites: cellular and molecular mechanisms , 2003, Nature Reviews Immunology.

[7]  Xia Zhang,et al.  Dynamic and Transient Remodeling of the Macrophage IL-10 Promoter during Transcription1 , 2006, The Journal of Immunology.

[8]  A. Mantovani,et al.  Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals , 2009, Proceedings of the National Academy of Sciences.

[9]  Mason A. Porter,et al.  Multilayer Analysis and Visualization of Networks , 2014, J. Complex Networks.

[10]  Joaquín Dopazo,et al.  Web-based network analysis and visualization using CellMaps , 2016, Bioinform..

[11]  A. Barabasi,et al.  Network medicine : a network-based approach to human disease , 2010 .

[12]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[13]  Reinhard Schneider,et al.  Arena3D: visualizing time-driven phenotypic differences in biological systems , 2012, BMC Bioinformatics.

[14]  Minoru Kanehisa,et al.  KEGG: new perspectives on genomes, pathways, diseases and drugs , 2016, Nucleic Acids Res..

[15]  Hyojin Kim,et al.  TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions , 2017, Nucleic Acids Res..

[16]  Henning Hermjakob,et al.  The Reactome pathway knowledgebase , 2013, Nucleic Acids Res..

[17]  Hendra Susanto,et al.  Altered plasma acylcarnitine and amino acid profiles in type 2 diabetic kidney disease , 2016, Metabolomics.

[18]  Karin Breuer,et al.  InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation , 2012, Nucleic Acids Res..

[19]  Qi Wang,et al.  3DScapeCS: application of three dimensional, parallel, dynamic network visualization in Cytoscape , 2013, BMC Bioinformatics.

[20]  Anton J. Enright,et al.  Visualizing genome and systems biology: technologies, tools, implementation techniques and trends, past, present and future , 2015, GigaScience.

[21]  Morgan C. Giddings,et al.  Defining functional DNA elements in the human genome , 2014, Proceedings of the National Academy of Sciences.

[22]  Igor Jurisica,et al.  NAViGaTOR: Network Analysis, Visualization and Graphing Toronto , 2009, Bioinform..

[23]  Tamara Munzner,et al.  Cerebral: a Cytoscape plugin for layout of and interaction with biological networks using subcellular localization annotation , 2007, Bioinform..

[24]  Daniel E. Kee,et al.  Comparing Interactive Web-Based Visualization Rendering Techniques , 2012 .

[25]  Selim Kalayci,et al.  iCAVE: an open source tool for visualizing biomolecular networks in 3D, stereoscopic 3D and immersive 3D , 2017, GigaScience.

[26]  Zhenjun Hu,et al.  Visant: an Integrative Framework for Networks in Systems Biology , 2008 .

[27]  Aedín C. Culhane,et al.  Dimension reduction techniques for the integrative analysis of multi-omics data , 2016, Briefings Bioinform..

[28]  H. Kitano.  Systems Biology: A Brief Overview , 2002, Science.

[29]  T. Tuschl,et al.  Tumorigenesis and Neoplastic Progression MicroRNA-Mediated Down-Regulation of PRDM 1 / Blimp-1 in Hodgkin / Reed-Sternberg Cells : A Potential Pathogenetic Lesion in Hodgkin Lymphomas , 2010 .

[30]  Réka Albert,et al.  Near linear time algorithm to detect community structures in large-scale networks. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[31]  Jonathan L. Robinson,et al.  Integrative analysis of human omics data using biomolecular networks. , 2016, Molecular bioSystems.

[32]  Li Ni,et al.  The Gene Ontology's Reference Genome Project: A Unified Framework for Functional Annotation across Species , 2009, PLoS Comput. Biol..

[33]  Neil Swainston,et al.  Recon 2.2: from reconstruction to model of human metabolism , 2016, Metabolomics.

[34]  Paula Ribeiro,et al.  miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis , 2016, Nucleic Acids Res..

[35]  Anton J. Enright,et al.  Network visualization and analysis of gene expression data using BioLayout Express3D , 2009, Nature Protocols.

[36]  Matthieu Latapy,et al.  Computing Communities in Large Networks Using Random Walks , 2004, J. Graph Algorithms Appl..

[37]  Martin Rosvall,et al.  An information-theoretic framework for resolving community structure in complex networks , 2007, Proceedings of the National Academy of Sciences.

[38]  Rafael C. Jimenez,et al.  The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases , 2013, Nucleic Acids Res..

[39]  Anushya Muruganujan,et al.  PANTHER version 10: expanded protein families and functions, and analysis tools , 2015, Nucleic Acids Res..

[40]  Georgios A. Pavlopoulos,et al.  BMC Systems Biology , 2022 .

[41]  J. Berzofsky,et al.  Role of T‐Cell Derived Cytokines in the Downregulation of Immune Responses in Parasitic and Retroviral Infection , 1992, Immunological reviews.

[42]  Edward M. Reingold,et al.  Graph drawing by force‐directed placement , 1991, Softw. Pract. Exp..

[43]  Ronald W. Davis,et al.  Transcriptional regulation and function during the human cell cycle , 2001, Nature Genetics.

[44]  Jianguo Xia,et al.  Computational Approaches for Integrative Analysis of the Metabolome and Microbiome , 2017, Metabolites.

[45]  J. Xia,et al.  Comprehensive Transcriptome Meta-analysis to Characterize Host Immune Responses in Helminth Infections , 2016, PLoS neglected tropical diseases.

[46]  Damian Szklarczyk,et al.  The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible , 2016, Nucleic Acids Res..

[47]  Paul T. Groth,et al.  The ENCODE (ENCyclopedia Of DNA Elements) Project , 2004, Science.

[48]  Jianguo Xia,et al.  NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data , 2015, Nature Protocols.

[49]  M. Jacomy,et al.  ForceAtlas2, a Continuous Graph Layout Algorithm for Handy Network Visualization Designed for the Gephi Software , 2014, PloS one.