Matchmaking within DECIPHER
The phenotype-linked variant data in DECIPHER allows for effective patient matching. DECIPHER presents a powerful, flexible matching patient interface (Fig. 6B), which allows users to view DECIPHER records which overlap a deposited copy-number, sequence, or insertion variant, or a gene. The matching patient interface displays useful summary information about the potential matches, for example, for sequence variants, this is consequence, inheritance, and pathogenicity. To allow users to quickly identify the most prominent clinical features in overlapping patients, a list of phenotypes present in multiple matching patients is displayed. When viewing this interface from a patient record, additional lists showing which of the patient’s phenotypes are present or not recorded in matching patients are also displayed. This allows users to easily determine if there is a good phenotypic match between their patient and other matching patients. Beneath this is a table containing information about the individual matching patient records. The table columns can be sorted and all matching phenotypes are shown in bold.
Customisable data display:A series of filters are provided in the matching patient interface so that users can drill into the most relevant patient data. This allows users to filter on, for example, functional similarity, consequence, inheritance, and/or pathogenicity. This can be particularly useful when different variant consequences are associated with different syndromes (e.g. SCN2A , where loss of function variants are associated with nonspecific severe intellectual disability, and missense variants with infantile epileptic encephalopathy).
Functionally identical variants: If the same variant has previously been deposited to DECIPHER, a ‘Functionally Identical Variant’ interface is present, displaying variant pathogenicity and evidence, in addition to phenotype information from these patient records. This ensures that users are alerted to other patients carrying the same variant, and assists in the standardisation of variant classification across centres.
Discriminative phenotypes: The wealth of the phenotype-genotype linked data in DECIPHER also allows the aggregation of data associated with pathogenic variants in disease genes. Within DECIPHER, aggregated phenotype data is used to identify the most discriminating phenotypes associated with disease genes (Fig. 6C). Recognising distinctive clinical characteristics associated with a disorder can be key to a diagnosis. The interface presents a table displaying the percentage of phenotyped patients with sequence variants in a gene of interest with a particular phenotype, compared with the percentage of phenotyped patients in DECIPHER with the same phenotype, and the odds ratio andp -value from a Fisher’s exact test, which indicate the most discriminative phenotypes associated with a gene.
Clinician contact: If a matching patient is discovered, it is possible to contact the clinician responsible for the patient’s care through DECIPHER. DECIPHER depositors are able to send messages directly, and since October 2014, over 4,500 collaboration requests have been sent amongst these registered DECIPHER users. In the case where a user is not registered with DECIPHER, the DECIPHER team first moderates such contact requests, and if the request appears to be legitimate and appropriate, forwards the message to the clinician responsible for the patient, asking them to contact the requestor directly to discuss collaboration. Over 2,900 such contact requests have been sent since January 2018.