DECIPHER
Encyclopedia
DECIPHER is a web-based resource and database of array comparative genomic hybridization
data from analysis of patient DNA
. It documents submicroscopic
chromosome abnormalities, including microdeletions and duplications
, from over 6000 patients and maps them to the human genome
using the Ensembl
browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndrome
s, together with links to relevant scientific reports and support group
s.
An acronym of DatabasE of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources, DECIPHER was initiated in 2004 at the Sanger Institute in the United Kingdom, funded by the Wellcome Trust
. However it is supported by an international research consortium, with patient data contributed by more than 150 clinical genetics centres from 29 countries. Each centre is represented by an experienced clinical geneticist and a senior molecular cytogeneticist
.
DECIPHER was established in 2004 by Nigel Carter of the Wellcome Trust Sanger Institute and Helen Firth, a clinical genetics consultant at Addenbrooke's Hospital
in Cambridge
. It has three main aims:
As a tool for clinical geneticists, cytogeneticists and molecular biologists, DECIPHER is used to determine whether gene copy number variations identified in patients are of clinical significance. Members can visualise the genes within the region of DNA altered in their patients, and ascertain whether any are known to be implicated in disease. Chromosomal imbalances are a major cause of developmental delay, learning disabilities and congential abnormalities and — according to Emily Niemitz writing in Nature Genetics
— the database facilitates collaboration between researchers and clinicians who have patients with similar clinical characteristics, which can "assist in the discovery of new syndromes and in the recognition of genes of clinical importance."
based) of a patient's DNA. A potential microdeletion/microduplication may be identified, but the medical significance is not known. The clinician may enter the anonymised data into the restricted, password protected DECIPHER database and map the location and size of the chromosomal deletion/duplication to the reference genome
. Using DECIPHER, the clinician can then identify the specific genes affected by the deletion/duplication, determine whether any have known clinical significance (for example, whether tumour suppressor genes have been deleted), and view the region in the Ensembl genome browser to see whether there are any other consented patients in DECIPHER with overlapping deletion/duplications. This enables a better ascertainment of whether a copy number change is a normal polymorphic
variant, or the likely cause of the patient’s clinical symptoms. The clinician can then counsel the patient on the likely significance of the deletion/duplication, and its implications for their health.
Each patient's data is anonymized, and represented only by an ID with an associated genotype
and set of clinical symptoms (phenotype
s). Patient data is made accessible to other members of the consortium and viewable through Ensembl if a consent
form is signed by the patient. With informed consent, the anonymized deletion/duplication and phenotypes become available for view to DECIPHER consortium members and public users, with different levels of access (e.g. only logged users can see the contact details of the centre that entered the data). Public users who wish to find more information about a patient may send a request to DECIPHER, which then will forward it to the clinician coordinator responsible for the submitting center.
Most patients deposited in DECIPHER display genetic mutations with a very low occurrence in the general population. Hence the probability of the same clinicians encountering similar patients are also low. Since DECIPHER is opened to any accredited clinician or cytogeneticist from around the world, the chances of finding similar rare cases are significantly increased. This on-line sharing of clinical genetic information not only promotes better understanding of microdeletions/microduplications and their associated pathogenic phenotypes, it has also facilitated the discovery of new syndrome
s. As of June 2010, over 6130 patients have been entered into the DECIPHER database of which over 3280 are consented.
representatives from the field of human genetics, computational biology, ethics and law.
To ensure information privacy, data is served over an encrypted secure socket layer connection. Only trusted individuals from recognized medical research centres can access the identity of the center that submitted another patient (permitting them to contact the patient's clinicians should they wish to collaborate). Members of the public may browse consented anonymized patient data in DECIPHER and Ensembl, without the identity of the submitting centre being shown.
Array comparative genomic hybridization
Array-comparative genomic hybridization is a technique to detect genomic copy number variations at a higher resolution level than chromosome-based comparative genomic hybridization .-Process:DNA from...
data from analysis of patient DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. It documents submicroscopic
Submicroscopic
Submicroscopic is an English adjective used to describe particles of matter that cannot be seen under the most powerful optical microscope available. Atoms are examples of such submicroscopic particles....
chromosome abnormalities, including microdeletions and duplications
Gene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
, from over 6000 patients and maps them to the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
using the Ensembl
Ensembl
Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent completion of the Human Genome Project...
browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
s, together with links to relevant scientific reports and support group
Support group
In a support group, members provide each other with various types of help, usually nonprofessional and nonmaterial, for a particular shared, usually burdensome, characteristic...
s.
An acronym of DatabasE of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources, DECIPHER was initiated in 2004 at the Sanger Institute in the United Kingdom, funded by the Wellcome Trust
Wellcome Trust
The Wellcome Trust was established in 1936 as an independent charity funding research to improve human and animal health. With an endowment of around £13.9 billion, it is the United Kingdom's largest non-governmental source of funds for biomedical research...
. However it is supported by an international research consortium, with patient data contributed by more than 150 clinical genetics centres from 29 countries. Each centre is represented by an experienced clinical geneticist and a senior molecular cytogeneticist
Molecular cytogenetics
Molecular cytogenetics involves the combination of molecular biology and cytogenetics. In general this involves the use of a series of techniques referred to as fluorescence in situ hybridization, or FISH, in which DNA probes are labeled with different colored fluorescent tags to visualize one or...
.
Aims
Addenbrooke's Hospital
Addenbrooke's Hospital is an internationally renowned teaching hospital in Cambridge, England, with strong links to the University of Cambridge. It was founded in 1766 on Trumpington Street with £4,500 from the will of Dr John Addenbrooke, a fellow of St Catharine's College...
in Cambridge
Cambridge
The city of Cambridge is a university town and the administrative centre of the county of Cambridgeshire, England. It lies in East Anglia about north of London. Cambridge is at the heart of the high-technology centre known as Silicon Fen – a play on Silicon Valley and the fens surrounding the...
. It has three main aims:
- Increasing medical and scientific knowledge about chromosomal microdeletions/duplications,
- Improving medical care and genetic advice for affected individuals/families, and
- Facilitating research into the study of genes that influence human development and health.
As a tool for clinical geneticists, cytogeneticists and molecular biologists, DECIPHER is used to determine whether gene copy number variations identified in patients are of clinical significance. Members can visualise the genes within the region of DNA altered in their patients, and ascertain whether any are known to be implicated in disease. Chromosomal imbalances are a major cause of developmental delay, learning disabilities and congential abnormalities and — according to Emily Niemitz writing in Nature Genetics
Nature Genetics
Nature Genetics is a scientific journal concerning genetics. It is published by Nature Publishing Group, and was founded as part of the Nature family of journal in 1992. The 2010 impact factor is 36.377. Its sister journal is Nature Reviews Genetics.- External links :*...
— the database facilitates collaboration between researchers and clinicians who have patients with similar clinical characteristics, which can "assist in the discovery of new syndromes and in the recognition of genes of clinical importance."
Process
Patients are entered into DECIPHER by registered consortium members. Typically a clinical geneticist arranges for a chromosome analysis (usually microarrayMicroarray
A microarray is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening methods.Types of microarrays include:...
based) of a patient's DNA. A potential microdeletion/microduplication may be identified, but the medical significance is not known. The clinician may enter the anonymised data into the restricted, password protected DECIPHER database and map the location and size of the chromosomal deletion/duplication to the reference genome
Reference genome
A reference genome is a digital nucleic acid sequence database, assembled by scientists as a representative example of a species' genetic code. As they are often assembled from the sequencing of DNA from a number of donors, reference genomes do not accurately represent the genetic code of any...
. Using DECIPHER, the clinician can then identify the specific genes affected by the deletion/duplication, determine whether any have known clinical significance (for example, whether tumour suppressor genes have been deleted), and view the region in the Ensembl genome browser to see whether there are any other consented patients in DECIPHER with overlapping deletion/duplications. This enables a better ascertainment of whether a copy number change is a normal polymorphic
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
variant, or the likely cause of the patient’s clinical symptoms. The clinician can then counsel the patient on the likely significance of the deletion/duplication, and its implications for their health.
Each patient's data is anonymized, and represented only by an ID with an associated genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
and set of clinical symptoms (phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s). Patient data is made accessible to other members of the consortium and viewable through Ensembl if a consent
Informed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
form is signed by the patient. With informed consent, the anonymized deletion/duplication and phenotypes become available for view to DECIPHER consortium members and public users, with different levels of access (e.g. only logged users can see the contact details of the centre that entered the data). Public users who wish to find more information about a patient may send a request to DECIPHER, which then will forward it to the clinician coordinator responsible for the submitting center.
Most patients deposited in DECIPHER display genetic mutations with a very low occurrence in the general population. Hence the probability of the same clinicians encountering similar patients are also low. Since DECIPHER is opened to any accredited clinician or cytogeneticist from around the world, the chances of finding similar rare cases are significantly increased. This on-line sharing of clinical genetic information not only promotes better understanding of microdeletions/microduplications and their associated pathogenic phenotypes, it has also facilitated the discovery of new syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
s. As of June 2010, over 6130 patients have been entered into the DECIPHER database of which over 3280 are consented.
Ethics and privacy
The appropriate consent to enter patient data into DECIPHER is obtained by the submitting clinician. Patient consent can be withdrawn at any time, and their data is removed. Often children's records are displayed with the consent of their parents of guardians. DECIPHER advises that, when the child reaches the age of sixteen years, he or she be made aware of the entry and be given the opportunity to withdraw or continue as a participant. Each member centre that uses DECIPHER obtains ethical approval from a research ethics committee in their own institution or country, where applicable. In the UK, the Information Commissioner's Office has been notified about DECIPHER in accordance with the Data Protection Act 1998. The project is overseen by an advisory boardAdvisory board
An advisory board is a body that advises the board of directors and management of a corporation but does not have authority to vote on corporate matters, nor a legal fiduciary responsibility...
representatives from the field of human genetics, computational biology, ethics and law.
To ensure information privacy, data is served over an encrypted secure socket layer connection. Only trusted individuals from recognized medical research centres can access the identity of the center that submitted another patient (permitting them to contact the patient's clinicians should they wish to collaborate). Members of the public may browse consented anonymized patient data in DECIPHER and Ensembl, without the identity of the submitting centre being shown.