Cross-species Conservation of context-specific networks.

Robert Pesch,Ralf Zimmer

doi:10.1186/s12918-016-0304-1

Abstract

BackgroundMany large data compendia on context-specific high-throughput genomic and regulatory data have been made available by international research consortia such as ENCODE, TCGA, and Epigenomics Roadmap. The use of these resources is impaired by the sheer size of the available big data and big metadata. Many of these context-specific data can be modeled as data derived regulatory networks (DDRNs) representing the complex and complicated interactions between transcription factors and target genes. These DDRNs are useful for the understanding of regulatory mechanisms and helpful for interpreting biomedical data.ResultsThe Cross-species Conservation framework (CroCo) provides a network-oriented view on the ENCODE regulatory data (CroCo network repository), convenient ways to access and browse networks and metadata, and a method to combine networks across compendia, experimental techniques, and species (CroCo tool suite). DDRNs can be combined with additional information and networks derived from the literature, curated resources, and computational predictions in order to enable detailed exploration and cross checking of regulatory interactions. Applications of the CroCo framework range from simple evidence look-up for user-defined regulatory interactions to the identification of conserved sub-networks in diverse cell-lines, conditions, and even species.ConclusionCroCo adds an intuitive unifying view on the data from the ENCODE projects via a comprehensive repository of derived context-specific regulatory networks and enables flexible cross-context, cross-species, and cross-compendia comparison via a basis set of analysis tools.The CroCo web-application and Cytoscape plug-in are freely available at: http://services.bio.ifi.lmu.de/croco-web. The web-page links to a detailed system description, a user guide, and tutorial videos presenting common use cases of the CroCo framework.

Highlights

Many large data compendia on context-specific high-throughput genomic and regulatory data have been made available by international research consortia such as ENCODE, TCGA, and Epigenomics Roadmap
With Cross-species Conservation framework (CroCo), we present a repository of pre-computed regulatory networks and a user-friendly tool suite for the efficient cross-species and cross-context comparison of Derived Regulatory Networks (DDRNs) from the ENCODE data sets and regulatory networks derived from the literature, curated resources, and computational predictions
In the following use cases, we demonstrate the application of the CroCo Cytoscape plug-in and the CroCo web-application to the identification of conserved and context-specific regulations, network features, and sub-networks

Summary

Introduction

Many large data compendia on context-specific high-throughput genomic and regulatory data have been made available by international research consortia such as ENCODE, TCGA, and Epigenomics Roadmap. The use of these resources is impaired by the sheer size of the available big data and big metadata Many of these context-specific data can be modeled as data derived regulatory networks (DDRNs) representing the complex and complicated interactions between transcription factors and target genes. DDRNs are graphs (V,E) defined on a common set of vertices V and specific sets of edges E between them They provide an abstracted view on the data and are used as the main tool to enable a straightforward analysis, comparison and integration of data sets across different contexts, experimental techniques, and cell-lines, even across different compendia and across different species via basic network operations. Tools and web-services like NetWAS and GIANT [19] allow to infer and browse tissue-specific functional networks in order to identify tissue-specific disease-gene associations

Results

Discussion

Conclusion