IIS--Integrated Interactome System: a web-based platform for the annotation, analysis and visualization of protein-metabolite-gene-drug interactions by integrating a variety of data sources and tools

PLoS One. 2014 Jun 20;9(6):e100385. doi: 10.1371/journal.pone.0100385. eCollection 2014.

Abstract

Background: High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted.

Results: We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web.

Conclusions: We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two-hybrid, proteomics and metabolomics datasets, but it is also extendable to other datasets. IIS is freely available online at: http://www.lge.ibi.unicamp.br/lnbio/IIS/.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein*
  • Female
  • Humans
  • Internet*
  • Metabolomics
  • Molecular Sequence Annotation*
  • NIMA-Related Kinases
  • Neoplasm Metastasis
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Pharmaceutical Preparations / metabolism*
  • Protein Interaction Maps*
  • Protein Serine-Threonine Kinases / metabolism
  • Proteomics
  • Saccharomyces cerevisiae / metabolism
  • Systems Biology / methods*
  • User-Computer Interface*

Substances

  • Pharmaceutical Preparations
  • NEK6 protein, human
  • NIMA-Related Kinases
  • Protein Serine-Threonine Kinases

Grants and funding

This work was supported by Fundação de Amparo à Pesquisa do Estado São Paulo (FAPESP), Conselho Nacional de Pesquisa e Desenvolvimento (CNPq), Brazilian Biosciences National Laboratory (LNBio) and Center for Computational Engineering and Sciences at UNICAMP/Brazil (FAPESP/CEPID project #2013/08293-7). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.