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GenomeDiver: a platform for phenotype-guided medical genomic diagnosis



Making a diagnosis from clinical genomic sequencing requires well-structured phenotypic data to guide genotype interpretation. A patient’s phenotypic features can be documented using the Human Phenotype Ontology (HPO), generating terms used to prioritize genes potentially causing the patient’s disease. We have developed GenomeDiver to provide a user interface for clinicians that allows more effective collaboration with the clinical diagnostic laboratory, with the goal of improving the success of the diagnostic process.


GenomeDiver uses genomic data to prompt reverse phenotyping of patients undergoing genetic testing, enriching the amount and quality of structured phenotype data for the diagnostic laboratory, and helping clinicians to explore and flag diseases potentially causing their patient’s presentation.


We show how GenomeDiver communicates the clinician’s informed insights to the diagnostic lab in the form of HPO terms for interpretation of genomic sequencing data. We describe our user-driven design process, the engineering of the software for efficiency, security and portability, and examples of the performance of GenomeDiver using genomic testing data.


GenomeDiver is a first step in a new approach to genomic diagnostics that enhances laboratory–clinician interactions, with the goal of directly engaging clinicians to improve the outcome of genomic diagnostic testing.

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Fig. 1: The clinician interface for GenomeDiver.
Fig. 2: Following the categorization of the Human Phenotype Ontology (HPO) terms, a second Exomiser run reprioritizes variants, genes, and associated diseases.

Data availability

The GenomeDiver software is available at The patient genomes and HPO terms used in the user experience trial will be available as part of the Clinical Sequencing Evidence-Generating Research (CSER) data deposition on the Analysis, Visualization, and Informatics Lab-space (ANViL,


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Research reported in this publication was part of the NYCKidSeq project, supported by the National Human Genome Research Institute and National Institute for Minority Heath and Health Disparities of the National Institutes of Health under award number 1U01HG0096108.

Author information




Conceptualization: N.M.P., C.S., K.S., F.B., N.S.A-H., K.B., J.A.O., S.A.S., B.D.G., E.E.K., V.J., T.B., J.M.G. Data curation: V.J. Formal analysis: N.M.P., F.B., C.G., T.B., J.M.G. Funding acquisition: C.R.H., M.W., B.D.G., E.E.K. Investigation: N.M.P., C.S., K.S., F.B., T.B., J.M.G. Methodology: N.M.P., C.S., K.S., F.B., C.G., V.J., T.B., J.M.G. Project administration: N.M.P., F.B., G.B., E.E.K., C.G., V.J., T.B., J.M.G. Resources: C.R.H., M.W., B.D.G., E.E.K., C.G., V.J., T.B., J.M.G. Software: N.M.P., C.S., K.S., F.B., J.M.G. Supervision: G.B., E.E.K., C.G., J.M.G. Validation: N.M.P., C.S., K.S., F.B., N.S.A-H., G.A.D., M.W., B.D.G. Visualization: N.P., C.S., K.S., F.B., J.M.G. Writing—original draft: N.M.P., CS KS C.G., J.M.G. Writing—review & editing: N.M.P., C.S., K.S., F.B., N.S.A-H., GB K.B., G.A.D., J.A.O., S.A.S., C.R.H., M.W., B.D.G., E.E.K., C.G., T.B., J.M.G.

Corresponding author

Correspondence to John M. Greally.

Ethics declarations

Ethics declaration

The NYCKidSeq project ( Identifier: NCT03738098) was approved by the Institutional Review Boards (IRBs) of Icahn School of Medicine at Mount Sinai and Albert Einstein College of Medicine. Informed consent was obtained from all study participants. All data were de-identified for downstream research, including the GenomeDiver user experience trial.

Competing interests

N.S.A.-H. was previously employed at Regeneron Pharmaceuticals and has received an honorarium from Genentech. E.E.K. has received speaker honoraria from Regeneron Pharmaceuticals and Illumina, Inc. The other authors declare no competing interests.

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Pearson, N.M., Stolte, C., Shi, K. et al. GenomeDiver: a platform for phenotype-guided medical genomic diagnosis. Genet Med (2021).

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