Broad Institute
Our Knowledge Provider will integrate human genetic evidence that causally links molecular or cellular abnormalities to complex human disease. Although many complex disease genetic associations have been identified by genome wide association studies (GWAS)1, incorporation of these data in their current state into Translator is impeded by two major gaps:
(a) Complex disease associations are statistical, in contrast to the qualitative relationships often curated for rare diseases (e.g. in ClinVar2). No repositories currently integrate statistical relationships across many GWAS to summarize how likely each variant is to have a “true” disease association.
(b) Most complex disease associations cannot yet be linked to a molecular or cellular process, or even (in most cases) a gene3. Datasets and methods to predict these linkages have emerged in recent years, but no repositories yet exist that integrate these emerging resources, and approaches for representing them are not yet standardized.
To address these gaps, we will develop new standards and approaches to represent, curate, and evaluate the multiple lines of evidence that now exist to translate GWAS associations to molecular or cellular abnormalities that underlie disease. We will rely upon the collaborative network and software we have built for the Knowledge Portal Network (KPN; kp4cd.org), a set of web portals and Smart APIs for complex disease genetic and functional genomic data. Seven complex disease research consortia use the KPN as the official means to distribute their data and knowledge, distinguishing the KPN from other resources (such as the NHGRI/EBI GWAS catalog4) that aggregate data without direct investment by the experts who produced it.