STITCH: interaction networks of chemicals and proteins

Kuhn, Michael; Mering, Christian von; Campillos, Mónica; Jensen, Lars Juhl; Bork, Peer

doi:10.1093/nar/gkm795

Cited by 710 publications

(600 citation statements)

References 30 publications

(38 reference statements)

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“…To include this aspect of microbial interactions in global ecosystems biology, an integrated effort is needed to detect both the production of, and the response to, the plethora of small molecules that are produced by these organisms. Environmental metabolomics approaches, combined with metagenomic, meta-transcriptomic [58] and metaproteomic [59,60] data, should eventually allow the reconstruction of ecosystem-wide combined protein small-molecule networks, similar to those that have been achieved for single organisms (see Further information for a link to the STITCH chemical-protein interactions resource [61]). This approach could ultimately result in the molecular modelling of community multicellular behaviour types other than quorum sensing, such as dispersal, nutrient acquisition and biofilm formation [62].…”

Section: Cell-cell Signalling -Communication and Quorum Sensingmentioning

confidence: 99%

Molecular eco-systems biology: towards an understanding of community function

Raes¹,

Bork²

2008

Nat Rev Microbiol

344

274

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| Systems-biology approaches, which are driven by genome sequencing and high-throughput functional genomics data, are revolutionizing single-cell-organism biology. With the advent of various high-throughput techniques that aim to characterize complete microbial ecosystems (metagenomics, meta-transcriptomics and meta-metabolomics), we propose that the time is ripe to consider molecular systems biology at the ecosystem level (eco-systems biology). Here, we discuss the necessary data types that are required to unite molecular microbiology and ecology to develop an understanding of community function and discuss the potential shortcomings of these approaches.Over the past decade, the advent of robotics has enabled a paradigm shift in molecular biology: a change of emphasis from reductionistic approaches and 'singleprotein' studies to global investigations of increasingly more complex systems of molecules and their interrelationships. These 'systems approaches' are used to investigate processes as a whole and enable models to be built to predict the behaviour of a system in response to various external cues, disturbances or modifications of its composition [1]. After ground-breaking work on the properties of small networks that consisted of a few genes, the wiring of complete cells and microbial organisms is now being investigated and modelled [2,3]. However, as free-living organisms constantly interact with each other and the environment, systems biologists are already looking towards the next big challengeunravelling the complexity of complete ecosystems.A microbial ecosystem can be defined as a system that consists of all the microorganisms that live in a certain area or niche and that function together in the context of the other biotic (plants and animals) and abiotic (temperature, chemical composition and structure of the surroundings) factors of that niche. Communities range from being simple (for example, one-or two-speciesdominated bioreactors and biofilms that are growing on ore-mine effluents or medical implants) to complex (for example, symbiotic human gut flora, plant rhizospheres, soil communities and ocean dwelling or even airborne microorganisms, such as those present in clouds). The complexity of the interactions in ecosystems depends on the number of species and the population structure, variation in food and energy supply and the geography of the habitat [4]. Eco-systems biology seeks to understand, as a whole, the immensely complex set of molecular processes and interactions that contribute to ecosystem functioning -the total sum of ecosystem-level processes, such as matter, nutrient and energy cycling [5]. This understanding should ultimately lead to predictive modelling of ecosystems, allowing the in silico investigation of ecosystem properties. Important issues that could be addressed by an ecosystems approach include estimating the relative importance of ecosystem members in ecosystem functioning and productivity, the effect of nutrient availability on species composition or the resil...

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Section: Cell-cell Signalling -Communication and Quorum Sensingmentioning

confidence: 99%

Molecular eco-systems biology: towards an understanding of community function

Raes¹,

Bork²

2008

Nat Rev Microbiol

344

274

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“…Again, this information is available from different resources, but there are some attempts to collate them into a single resource. The database STITCH (search tool for interactions of chemicals) (http://stitch.embl.de/; Kuhn et al, 2008) is one such tool, combining information on the interaction of chemicals and proteins from multiple sources. Chemicals are linked to other chemicals and proteins by evidence derived from experiments, databases and the literature, providing an overview of the part of the 'interactome' involved in the expression of the trait of interest.…”

Section: Identifying Connections In the Systemmentioning

confidence: 99%

The integration of ‘omic’ disciplines and systems biology in cattle breeding

Berry

Meade

Mullen

et al. 2011

Animal

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Enormous progress has been made in the selection of animals, including cattle, for specific traits using traditional quantitative genetics approaches. Nevertheless, considerable variation in phenotypes remains unexplained, and therefore represents potential additional gain for animal production. In addition, the paradigm shift in new disciplines now being applied to animal breeding represents a powerful opportunity to prise open the 'black box' underlying the response to selection and fully understand the genetic architecture controlling the traits of interest. A move away from traditional approaches of animal breeding toward systems approaches using integrative analysis of data from the 'omic' disciplines represents a multitude of exciting opportunities for animal breeding going forward as well as providing alternatives for overcoming some of the limitations of traditional approaches such as the expressed phenotype being an imperfect predictor of the individual's true genetic merit, or the phenotype being only expressed in one gender or late in the lifetime of an animal. This review aims to discuss these opportunities from the perspective of their potential application and contribution to cattle breeding. Harnessing the potential of this paradigm shift also poses some new challenges for animal scientists -and they will also be discussed.

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“…To annotate the NPC upregulated genes with FDAapproved drug targets, we integrated databases from STITCH (25) and Drug Bank (26). We thereby derived 566 and 827 drug target upregulated and downregulated genes, respectively.…”

Section: Fda-approved Drug Targetsmentioning

confidence: 99%

From NPC Therapeutic Target Identification to Potential Treatment Strategy

Lan

Chen

Lin

et al. 2010

Molecular Cancer Therapeutics

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Nasopharyngeal carcinoma (NPC) is relatively rare in Western countries but is a common cancer in southern Asia. Many differentially expressed genes have been linked to NPC; however, how to prioritize therapeutic targets and potential drugs from unsorted gene lists remains largely unknown. We first collected 558 upregulated and 993 downregulated NPC genes from published microarray data and the primary literatures. We then postulated that conversion of gene signatures into the protein-protein interaction network and analyzing the network topologically could provide insight into key regulators involved in tumorigenesis of NPC. Of particular interest was the presence of cliques, called fully connected subgraphs, in the inferred NPC networks. These clique-based hubs, connecting with more than three queries and ranked higher than other nodes in the NPC protein-protein interaction network, were further narrowed down by pathway analysis to retrieve 24 upregulated and 6 downregulated bottleneck genes for predicting NPC carcinogenesis. Moreover, additional oncogenes, tumor suppressor genes, genes involved in protein complexes, and genes obtained after functional profiling were merged with the

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STITCH: interaction networks of chemicals and proteins

Cited by 710 publications

References 30 publications

Molecular eco-systems biology: towards an understanding of community function

Molecular eco-systems biology: towards an understanding of community function

The integration of ‘omic’ disciplines and systems biology in cattle breeding

From NPC Therapeutic Target Identification to Potential Treatment Strategy

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