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.