title: RASopathies: Presentation at the Genome, Interactome, and Phenome Levels.
abstract: Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syndromes: Noonan, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, cardiofaciocutaneous, and Legius and Costello syndrome. The STRING tool was used for the identification of protein interactions. Six RASopathy syndromes were found to be associated with 12 causative genes. We constructed an interactome of RASopathy proteins and their neighbors and developed a database of 328 clinical symptoms. The collected data was presented at genome, interactome, and phenome levels and as an integrated network of all 3 data types. The present study provides a baseline for future studies of associations between interactome and phenome in RASopathies and could serve as a novel approach to analyze phenotypically and genetically related diseases.
authors.affiliation: Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia.
authors.forename: Urska
authors.initials: U
authors.lastname: Pevec
authors.affiliation: Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia.
authors.forename: Neva
authors.initials: N
authors.lastname: Rozman
authors.affiliation: Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia.
authors.forename: Blaz
authors.initials: B
authors.lastname: Gorsek
authors.affiliation: Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domzale, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kunej
keywords: Gene network; Genetic diseases; Interactome; Noonan syndrome; Phenome; RASopathies