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PMID: 26220709 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Facilitating collaboration in rare genetic disorders through effective matchmaking in DECIPHER.

Human mutation ·Vol. 36 ·No. 10 ·2015-10-00 ·Pages 941-9

Chatzimichali EA, Brent S, Hutton B, Perrett D, Wright CF, Bevan AP, Hurles ME, Firth HV, Swaminathan GJ

Abstract

DECIPHER (https://decipher.sanger.ac.uk) is a web-based platform for secure deposition, analysis, and sharing of plausibly pathogenic genomic variants from well-phenotyped patients suffering from genetic disorders. DECIPHER aids clinical interpretation of these rare sequence and copy-number variants by providing tools for variant analysis and identification of other patients exhibiting similar genotype-phenotype characteristics. DECIPHER also provides mechanisms to encourage collaboration among a global community of clinical centers and researchers, as well as exchange of information between clinicians and researchers within a consortium, to accelerate discovery and diagnosis. DECIPHER has contributed to matchmaking efforts by enabling the global clinical genetics community to identify many previously undiagnosed syndromes and new disease genes, and has facilitated the publication of over 700 peer-reviewed scientific publications since 2004. At the time of writing, DECIPHER contains anonymized data from ∼250 registered centers on more than 51,500 patients (∼18000 patients with consent for data sharing and ∼25000 anonymized records shared privately). In this paper, we describe salient features of the platform, with special emphasis on the tools and processes that aid interpretation, sharing, and effective matchmaking with other data held in the database and that make DECIPHER an invaluable clinical and research resource.

Keywords
MatchMaker Exchange genetic disorders genotype-phenotype correlation rare diseases
MeSH Terms
Databases, Genetic Genetic Predisposition to Disease/genetics Genetic Variation Humans Information Dissemination/methods Phenotype Rare Diseases/genetics Software User-Computer Interface Web Browser
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chatzimichali Eleni A
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Brent Simon
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Hutton Benjamin
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Perrett Daniel
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Wright Caroline F
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Bevan Andrew P
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Hurles Matthew E
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
Firth Helen V
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom. | Cambridge University Department of Medical Genetics, Addenbrooke's Hospital, Cambridge, CB2 2QQ, United Kingdom.
Swaminathan Ganesh J
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
References (36)
36 references, click to expand
  1. Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience.
    Hum Mutat. 2012 May;33(5):787-96 PMID: 22331816
  2. Large-scale objective association of mouse phenotypes with human symptoms through structural variation identified in patients with developmental disorders.
    Hum Mutat. 2012 May;33(5):874-83 PMID: 22396327
  3. DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders.
    Hum Mol Genet. 2012 Oct 15;21(R1):R37-44 PMID: 22962312
  4. 12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech.
    Eur J Hum Genet. 2013 Jan;21(1):82-8 PMID: 22713806
  5. DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation.
    Nucleic Acids Res. 2014 Jan;42(Database issue):D993-D1000 PMID: 24150940
  6. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion.
    Hum Mutat. 2000;15(1):7-12 PMID: 10612815
  7. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.
    Nature. 2003 May 15;423(6937):293-8 PMID: 12714972
  8. Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features.
    J Med Genet. 2004 Apr;41(4):241-8 PMID: 15060094
  9. [Human chromosomes in tissue cultures].
    C R Hebd Seances Acad Sci. 1959 Jan 26;248(4):602-3 PMID: 13629913
  10. The Sequence Ontology: a tool for the unification of genome annotations.
    Genome Biol. 2005;6(5):R44 PMID: 15892872
  11. Assessing semantic similarity measures for the characterization of human regulatory pathways.
    Bioinformatics. 2006 Apr 15;22(8):967-73 PMID: 16492685
  12. GeneTests: an online genetic information resource for health care providers.
    J Med Libr Assoc. 2006 Jul;94(3):343-8 PMID: 16888670
  13. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability.
    Nat Genet. 2006 Sep;38(9):1032-7 PMID: 16906163
  14. Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation.
    Curr Opin Genet Dev. 2007 Jun;17(3):182-92 PMID: 17467974
  15. Novel deletions of 14q11.2 associated with developmental delay, cognitive impairment and similar minor anomalies in three children.
    J Med Genet. 2007 Sep;44(9):556-61 PMID: 17545556
  16. DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources.
    Am J Hum Genet. 2009 Apr;84(4):524-33 PMID: 19344873
  17. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.
    Nat Protoc. 2009;4(7):1073-81 PMID: 19561590
  18. 19q13.11 deletion syndrome: a novel clinically recognisable genetic condition identified by array comparative genomic hybridisation.
    J Med Genet. 2009 Sep;46(9):635-40 PMID: 19126570
  19. A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients.
    Eur J Hum Genet. 2009 Dec;17(12):1592-9 PMID: 19471318
  20. The Human Gene Mutation Database: providing a comprehensive central mutation database for molecular diagnostics and personalized genomics.
    Hum Genomics. 2009 Dec;4(2):69-72 PMID: 20038494
  21. A method and server for predicting damaging missense mutations.
    Nat Methods. 2010 Apr;7(4):248-9 PMID: 20354512
  22. The human phenotype ontology.
    Clin Genet. 2010 Jun;77(6):525-34 PMID: 20412080
  23. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor.
    Bioinformatics. 2010 Aug 15;26(16):2069-70 PMID: 20562413
  24. ClinVar: public archive of relationships among sequence variation and human phenotype.
    Nucleic Acids Res. 2014 Jan;42(Database issue):D980-5 PMID: 24234437
  25. Ensembl 2015.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D662-9 PMID: 25352552
  26. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D789-98 PMID: 25428349
  27. The UCSC Genome Browser database: 2015 update.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D670-81 PMID: 25428374
  28. Large-scale discovery of novel genetic causes of developmental disorders.
    Nature. 2015 Mar 12;519(7542):223-8 PMID: 25533962
  29. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data.
    Lancet. 2015 Apr 4;385(9975):1305-14 PMID: 25529582
  30. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
    Nat Genet. 2010 Sep;42(9):790-3 PMID: 20711175
  31. Characterising and predicting haploinsufficiency in the human genome.
    PLoS Genet. 2010 Oct;6(10):e1001154 PMID: 20976243
  32. The atypical 16p11.2 deletion: a not so atypical microdeletion syndrome?
    Am J Med Genet A. 2011 May;155A(5):1066-72 PMID: 21465664
  33. LOVD v.2.0: the next generation in gene variant databases.
    Hum Mutat. 2011 May;32(5):557-63 PMID: 21520333
  34. Characterization of copy number-stable regions in the human genome.
    Hum Mutat. 2011 Aug;32(8):947-55 PMID: 21542059
  35. A copy number variation morbidity map of developmental delay.
    Nat Genet. 2011 Sep;43(9):838-46 PMID: 21841781
  36. A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features.
    J Med Genet. 2012 Feb;49(2):104-9 PMID: 22180640
Article Info
Journal
Human mutation
Abbr.
Hum Mutat
ISSN
1098-1004
Published
2015-10-00
Epub
2015-00-20
Pages
941-9
Language
English
Region
United States
NLM ID
9215429
PMCID
PMC4832335
Subset
IM
Grants
Wellcome Trust · WT077008 · United Kingdom
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