Skip to main content
Figure 2 | BMC Medical Genomics

Figure 2

From: PhenoVar: a phenotype-driven approach in clinical genomics for the diagnosis of polymalformative syndromes

Figure 2

Future directions about Phenovar or similar software using the I-MPOS approach and data from real patients. A database containing phenotypic and encrypted genomic information of real patients with known or not-yet identified diagnoses can be made available (1). A patient with an unknown diagnosis presents in clinic. His encrypted ES data are obtained and his phenotype is assessed (2 α, β). The software automatically searches the “Encrypted Patients Database” using target patient’s assessed phenotype (3) thereby providing a first ranking of possible genetic conditions based on “phenotype weight” (4), (5). For all patients in the database meeting a specific phenotype-similarity threshold in relation to the proband, the software will compare the changes present in their genomes against the ones present in the genome of the patient seen in clinic (6). Matching the proband with the phenotypically similar subjects in the database based on similarity of their genetic changes (“mutation weight”) forms the basis of adjusting the first ranking to calculate the second ranking (6), (7). Subjects sharing adequate phenotypic characteristics who also share a genetic variant cluster together. As a result, a given match is indicative of the possibility that the target subject shares the same genetic condition with the matched other subject(s). After the second ranking, the information about the shared phenotype and genotype of the patients clustering together is accessible and can aid in reaching the diagnosis. It should be noted that “phenotype” (steps 2–5) is not limited to clinical traits but also refers to other levels of phenotype, such as a metabolomic profile. Also, the word “mutation” (steps 6, 7) can refer to variants in more than one genetic loci which are simultaneously present in all matched patients allowing one to explore the possibility of gene-gene interaction.

Back to article page