The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium

Dam, Teunis J. P. van; Wheway, Gabrielle; Slaats, Gisela G.; Huynen, Martijn A.; Giles, Rachel

doi:10.1186/2046-2530-2-7

Cited by 156 publications

(195 citation statements)

References 36 publications

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“…SYSCILIA Gold Standard contains genes considered to be ciliary only if evidence was published for ciliary localization (including basal body), function in ciliogenesis (including cilium-specific transcription) and involvement in ciliopathies [27]. We found a significant overlap between the two sets, with 70% of SCGSv1 genes (211 out of 303; p-value < 0.01, Fisher’s exact test) present in our collection.…”

Section: Resultsmentioning

confidence: 95%

A network-based approach to dissect the cilia/centrosome complex interactome

et al. 2014

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BackgroundCilia are microtubule-based organelles protruding from almost all mammalian cells which, when dysfunctional, result in genetic disorders called “ciliopathies”. High-throughput studies have revealed that cilia are composed of thousands of proteins. However, despite many efforts, much remains to be determined regarding the biological functions of this increasingly important complex organelle.ResultsWe have derived an online tool, from a systematic network-based approach to dissect the cilia/centrosome complex interactome (CCCI). The tool integrates all current available data into a model which provides an “interaction” perspective on ciliary function. We generated a network of interactions between human proteins organized into functionally relevant “communities”, which can be defined as groups of genes that are both highly inter-connected and strongly co-expressed. We then combined sequence and co-expression data in order to identify the transcription factors responsible for regulating genes within their respective communities. Our analyses have discovered communities significantly specialized for delegating specific biological functions such as mRNA processing, protein translation, folding and degradation processes that had never been associated with ciliary proteins until now.ConclusionsCCCI will allow us to clarify the roles of previously unknown ciliary functions, elucidate the molecular mechanisms underlying ciliary-associated phenotypes, and apply our knowledge of the functional roles of relatively uncharacterized molecular entities to disease phenotypes and new clinical applications.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-658) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 95%

A network-based approach to dissect the cilia/centrosome complex interactome

et al. 2014

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“…To benchmark our interaction dataset, we assembled a high quality reference list of 1554 proteins with previous evidence for centrosome or cilium association (Alves-Cruzeiro et al, 2014; van Dam et al, 2013), hereafter referred to as the centrosome and cilium database (CCDB; Table S1; Experimental Procedures ). 25% (336) of our BioID dataset consists of CCDB proteins (Table S1).…”

Section: Resultsmentioning

confidence: 99%

A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface

Gupta

Coyaud

Gonçalves

et al. 2015

Cell

475

528

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Summary Centrioles coordinate the primary microtubule organizing center of the cell and template the formation of cilia, thereby operating at a nexus of critical cellular functions. Here we use proximity-dependent biotinylation (BioID) to map the centrosome-cilium interface; with 58 bait proteins we generate a protein topology network comprising >7000 interactions. Analysis of interaction profiles coupled with high resolution phenotypic profiling implicates a number of new protein modules in centriole duplication, ciliogenesis and centriolar satellite biogenesis, and highlights extensive interplay between these processes. By monitoring dynamic changes in the centrosome-cilium protein interaction landscape during ciliogenesis, we also identify satellite proteins that support cilia formation. Systematic profiling of proximity interactions combined with functional analysis thus provides a rich resource for better understanding human centrosome and cilia biology. Similar strategies may be applied to other complex biological structures or pathways.

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“…Using these as the seed information, we prioritized zebrafish genes for ciliopathies using direct neighbors in DanioNet. To validate our predictions, we collected more recently reported ciliopathy genes (33 human genes and 39 zebrafish orthologs) from literatures published after 2013 (Supplementary Table S7) and known ciliary genes from the SYSCILIA gold standard (SCGSv1) database (51) (268 human genes and 333 zebrafish orthologs) (Supplementary Table S8). Among the top 100 predictions with corresponding human orthologs (Supplementary Table S9), we found seven recently reported ciliopathy genes (7% of precision) and 35 known ciliary genes (35% of precision).…”

Section: Resultsmentioning

confidence: 99%

“…We found that the known genes as well as the novel genes for ciliopathies were well connected with each other, although they were involved in diseases with diverse phenotypes, which is consistent with their overlap in causal genes and phenotypes. Interestingly, many of the intermediated nodes were also found to be implicated in ciliopathies when annotated using gold standards (Supplementary Table S8) or potential ciliary genes (Supplementary Table S13) from the SCGSv1 database (51). …”

Section: Resultsmentioning

confidence: 99%

Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource

Shim

Kim

et al. 2016

Nucleic Acids Res

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Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www.inetbio.org/danionet), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery.

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The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium

Cited by 156 publications

References 36 publications

A network-based approach to dissect the cilia/centrosome complex interactome

A network-based approach to dissect the cilia/centrosome complex interactome

A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface

Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource

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