The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button

Swertz, Morris A.; Dijkstra, Martijn; Adamusiak, Tomasz; Velde, K. Joeri van der; Kanterakis, Alexandros; Roos, Erik; Lops, Joris; Þórisson, Guðmundur Á.; Arends, Danny; Byelas, George; Muilu, Juha; Brookes, Anthony J.; Brock, E.O. de; Jansen, Ritsert C.; Parkinson, Helen

doi:10.1186/1471-2105-11-s12-s12

Cited by 111 publications

(99 citation statements)

References 20 publications

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“…The International DEB Patient Registry lists both published and unpublished DEB patients with their phenotypic details and associated COL7A1 genotypes, mutation consequences at the RNA and protein level, and potentially disease-modifying factors. The registry has been built on the MOLGENIS database platform, which has been shown to be easy to adapt and scale in various and high-throughput projects (Swertz and Jansen, 2007;Swertz et al, 2010aSwertz et al, , 2010b. These conditions will enable the study of genotype-phenotype correlation in larger cohorts of patients than previously possible.…”

Section: Dystrophic Epidermolysis Bullosa and The Type VII Collagen Gmentioning

confidence: 99%

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

et al. 2011

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Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder that can be inherited autosomal dominantly (DDEB) or recessively (RDEB) and covers a group of several distinctive phenotypes. A large number of unique COL7A1 mutations have been shown to underlie DEB. Although general genotype-phenotype correlation rules have emerged, many exceptions to these rules exist, compromising disease diagnosing and genetic counseling. We therefore constructed the International DEB Patient Registry (http://www.deb-central.org), aimed at worldwide collection and sharing of phenotypic and genotypic information on DEB. As of May 2011, this MOLGENIS-based registry contains detailed information on 508 published and 71 unpublished patients and their 388 unique COL7A1 mutations, and includes all combinations of mutations. The current registry RDEB versus DDEB ratio of 4:1, if compared to prevalence figures, suggests underreporting of DDEB in the literature. Thirty-eight percent of mutations stored introduce a premature termination codon (PTC) and 43% an amino acid change. Submission wizards allow users to quickly and easily share novel information. This registry will be of great help in disease diagnosing and genetic counseling and will lead to novel insights, especially in the rare phenotypes of which there is often lack of understanding. Altogether, this registry will greatly benefit the DEB patients.

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Section: Dystrophic Epidermolysis Bullosa and The Type VII Collagen Gmentioning

confidence: 99%

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

et al. 2011

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“…Additional segregation and phenotypic data from patients and/or controls can ultimately lead to a correct classification of all missense variants. The locus-specific CHD7 mutation database (available at www.CHD7.org; [Swertz et al, 2010]) provides a valuable source of information, as it contains both segregation and clinical data. Clinical data are important, because the phenotype of patients who undergo CHD7 analysis in a clinical diagnostic laboratory is not always highly suggestive of CHARGE syndrome [Bartels et al, 2010].…”

Section: A Novel Classification System For Chd7 Missense Variantsmentioning

confidence: 99%

A novel classification system to predict the pathogenic effects of CHD7 missense variants in CHARGE syndrome

et al. 2012

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CHARGE syndrome is characterized by the variable occurrence of multisensory impairment, congenital anomalies, and developmental delay, and is caused by heterozygous mutations in the CHD7 gene. Correct interpretation of CHD7 variants is essential for genetic counseling. This is particularly difficult for missense variants because most variants in the CHD7 gene are private and a functional assay is not yet available. We have therefore developed a novel classification system to predict the pathogenic effects of CHD7 missense variants that can be used in a diagnostic setting. Our classification system combines the results from two computational algorithms (PolyPhen-2 and Align-GVGD) and the prediction of a newly developed structural model of the chromo-and helicase domains of CHD7 with segregation and phenotypic data. The combination of different variables will lead to a more confident prediction of pathogenicity than was previously possible. We have used our system to classify 145 CHD7 missense variants. Our data show that pathogenic missense mutations are mainly present in the middle of the CHD7 gene, whereas benign variants are mainly clustered in the 5 and 3 regions. Finally, we show that CHD7 missense mutations are, in general, associated with a milder phenotype than truncating mutations.

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“…The power of this open, community-oriented approach, is shown by bioinformatics software initiatives such as BioPerl [Stajich et al, 2002] (http://www.bioperl.org) and BioJava [Holland et al, 2008] (http:// biojava.org). Examples of GEN2PHEN projects in this arena include software packages for easy creation of LSDBs and close partnership with the team developing Molgenis (http://www.molgenis.org), an open-source platform for rapid prototyping of genomics database software [Swertz et al, 2010] (see also Box 2).…”

Section: Toward a Unified G2p Data Infrastructurementioning

confidence: 99%

An informatics project and online “Knowledge Centre” supporting modern genotype-to-phenotype research

2011

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The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button

Cited by 111 publications

References 20 publications

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

A novel classification system to predict the pathogenic effects of CHD7 missense variants in CHARGE syndrome

An informatics project and online “Knowledge Centre” supporting modern genotype-to-phenotype research

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