title: 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.
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/.
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil; Laboratório de Genômica e Expressão, Departamento de Genética e Evolução, Instituto de Biologia, Unicamp, Campinas, São Paulo, Brazil.
authors.forename: Marcelo Falsarella
authors.initials: MF
authors.lastname: Carazzolle
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil.
authors.forename: Lucas Miguel
authors.initials: LM
authors.lastname: de Carvalho
authors.affiliation: Laboratório Nacional de Luz Síncrotron, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil.
authors.forename: Hugo Henrique
authors.initials: HH
authors.lastname: Slepicka
authors.affiliation: Laboratório de Genômica e Expressão, Departamento de Genética e Evolução, Instituto de Biologia, Unicamp, Campinas, São Paulo, Brazil.
authors.forename: Ramon Oliveira
authors.initials: RO
authors.lastname: Vidal
authors.affiliation: Laboratório de Genômica e Expressão, Departamento de Genética e Evolução, Instituto de Biologia, Unicamp, Campinas, São Paulo, Brazil.
authors.forename: Gonçalo Amarante Guimarães
authors.initials: GA
authors.lastname: Pereira
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kobarg
authors.affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil.
authors.forename: Gabriela Vaz
authors.initials: GV
authors.lastname: Meirelles
mesh_terms: D030562:Databases, Protein; D005260:Female; D006801:Humans; D020407:Internet; D055432:Metabolomics; D058977:Molecular Sequence Annotation; D000072379:NIMA-Related Kinases; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D014584:User-Computer Interface
chemical_list: D004364:Pharmaceutical Preparations; C459456:NEK6 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases