The similarity of inherited diseases (II): clinical and biological similarity between the phenotypic series
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RESEARCH ARTICLE
Open Access
The similarity of inherited diseases (II): clinical and biological similarity between the phenotypic series Alessio Gamba1, Mario Salmona1, Laura Cantù2 and Gianfranco Bazzoni1*
Abstract Background: Despite being caused by mutations in different genes, diseases in the same phenotypic series are clinically similar, as reported in Part I of this study. Here, in Part II, we hypothesized that the phenotypic series too might be clinically similar. Furthermore, on the assumption that gene mutations indirectly cause clinical phenotypes by directly affecting biological functions, we hypothesized that clinically similar phenotypic series might be biologically similar as well. Methods: To test these hypotheses, we generated a clinical similarity network and a set of biological similarity networks. In both types of network, the nodes represent the phenotypic series, and the edges linking the nodes indicate the similarity of the linked phenotypic series. The weight of each edge is proportional to a similarity coefficient, which depends on the clinical phenotypes and the biological features that are shared by the linked phenotypic series, in the clinical and biological similarity networks, respectively. Results: After assembling and analyzing the networks, we raised the threshold for the similarity coefficient, to retain edges of progressively greater weight. This way all the networks were gradually split into fragments, composed of phenotypic series with increasingly greater degrees of similarity. Finally, by comparing the fragments from the two types of network, we defined subsets of phenotypic series with varying types and degrees of clinical and biological correlation. Conclusions: Like the individual diseases, the phenotypic series too are clinically and biologically similar to each other. Furthermore, our findings unveil different modalities of correlation between the clinical manifestations and the biological features of the inherited diseases. Keywords: Gene mutations, Inherited diseases, Disease phenotypes, Biological processes, Network analysis, Ontologies
* Correspondence: [email protected] 1 Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, I-20156 Milan, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statu
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