Results
PhenomeCentral presently has 1,615 users that have entered 12,292 cases
(Figure 2 ) from all over the world. PhenomeCentral has become a
major data repository for several large scale rare disease research
programs, which have collectively contributed approximately 69% of the
total cases within PhenomeCentral. PhenomeCentral is endorsed by
multiple rare disease consortia and initiatives and is a recommended
resource by the International Rare Diseases Research Consortium (IRDiRC;
). The Care for Rare Canada Consortium (C4R; ) has a user base of 159
accounts which have deposited over 2,900 of their cases into
PhenomeCentral. Other groups contributing a significant number of cases
and using PhenomeCentral regularly include the Genetics of Development
Disorders Team (GAD; ), the NIH Undiagnosed Diseases Program and Network
(UDN; ), and the Telethon Institute of Genetics and Medicine (TIGEM; ).
The last two are members of the Undiagnosed Diseases Network
International (UDNI; ), which has endorsed PhenomeCentral as a data
sharing solution. Collectively, the RD research programs mentioned above
bring together 389 users that have contributed over 8,400 cases to date.
Currently, 5,554 cases in PhenomeCentral have a manually curated
candidate gene listed, spanning a total of 3,234 unique genes. Most
cases have a single candidate gene, with only 12% of cases listing two
or more genes as candidates. Additional genotypic data in the form of
VCF files are available in 1901 cases, which can be used to generate
matches between candidate genes and variants in genomic sequencing data.
The majority of cases in PhenomeCentral also have some degree of
computer-readable phenotyping (10250/12292, 83%). Of these cases, 94%
have two or more phenotypes documented, with a median of 8 phenotypic
terms per case. In total, 118,059 HPO annotations are documented across
this dataset, spanning across 7,938 unique HPO terms. When grouped into
general phenotypic categories, abnormalities of the nervous system are
the most commonly reported type of HPO term, followed by abnormalities
of the head or neck and abnormalities of the skeletal system
(Figure 3a) . More specifically, the most prevalent HPO terms
within this dataset (Figure 3b ) include global developmental
delay (2867/12292, 23%), seizures (1572/12292, 13%), and short stature
(1531/12292, 12%). In addition to HPO terms, many cases have additional
information entered, including growth charts (3005/12292, 24%), a
pedigree (2555/12292, 21%), and additional medical history information
(1972/12292, 16%).
A total of 4,665 matches have been made internally between
PhenomeCentral cases. In addition to internal matchmaking with other
PhenomeCentral cases, currently 70% of PhenomeCentral cases
(8479/12292) have been consented for matching with the other MME nodes.
Such cases submitted queries for over 2,900 unique candidate genes, and
these 8,479 cases collectively contained over 98,500 HPO annotations.
Queries involving PhenomeCentral as a node in the MME have resulted in
61,362 matches with other nodes, with the majority of these originating
from cases in GeneMatcher (40701/61362, 66%) and DECIPHER (17097/61362,
28%).
In collaboration with the MME, PhenomeCentral has enjoyed success in
facilitating matches leading to gene discovery (e.g., Chelban et al.,
2019; den Hoed et al., 2021; Faden et al., 2015; Ito et al., 2018;
Johnstone et al., 2017; Kernohan et al., 2017; Y.-R. Lee et al., 2020;
Lessel et al., 2020; Martinelli et al., 2018; Oud et al., 2017;
Salpietro et al., 2019; Simons et al., 2017; Skraban et al., 2017;
Stray-Pedersen et al., 2016; Vavassori et al., 2021), and, ultimately,
answers for families.