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DC Field | Value | Language |
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dc.contributor.author | Papadimitriou, Sofia | - |
dc.contributor.author | Gazzo, Andrea | - |
dc.contributor.author | Versbraegen, Nassim | - |
dc.contributor.author | Nachtegael, Charlotte | - |
dc.contributor.author | AERTS, Jan | - |
dc.contributor.author | Moreau, Yves | - |
dc.contributor.author | Van Dooren, Sonia | - |
dc.contributor.author | Nowe, Ann | - |
dc.contributor.author | Smits, Guillaume | - |
dc.contributor.author | Lenaerts, Tom | - |
dc.date.accessioned | 2019-08-13T09:41:08Z | - |
dc.date.available | 2019-08-13T09:41:08Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116(24), p. 11878-11887 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/1942/28953 | - |
dc.description.abstract | Notwithstanding important advances in the context of single-variant pathogenicity identification, novel breakthroughs in discerning the origins of many rare diseases require methods able to identify more complex genetic models. We present here the Variant Combinations Pathogenicity Predictor (VarCoPP), a machine-learning approach that identifies pathogenic variant combinations in gene pairs (called digenic or bilocus variant combinations). We show that the results produced by this method are highly accurate and precise, an efficacy that is endorsed when validating the method on recently published independent disease-causing data. Confidence labels of 95% and 99% are identified, representing the probability of a bilocus combination being a true pathogenic result, providing geneticists with rational markers to evaluate the most relevant pathogenic combinations and limit the search space and time. Finally, the VarCoPP has been designed to act as an interpretable method that can provide explanations on why a bilocus combination is predicted as pathogenic and which biological information is important for that prediction. This work provides an important step toward the genetic understanding of rare diseases, paving the way to clinical knowledge and improved patient care. | - |
dc.description.sponsorship | We thank all the members of the Interuniversity Institute for Bioinformatics in Brussels, especially the group of people interested in digenic and oligogenic diseases, for their comments and valuable suggestions. This work was supported by funding from the Actions de Recherche Concertees project Deciphering Oligo-and Polygenic Genetic Architecture in Brain Developmental Disorders (A.G., N.V., C.N., and T.L.); the European Regional Development Fund (ERDF) and the Brussels-Capital Region-Innoviris within the framework of the Operational Programme 2014-2020 through the ERDF-2020 project ICITY-RDI.BRU (27.002.53.01.4524; S.P., A.N., S.V.D., and T.L.); the Fonds de la Recherche Scientifique-Fonds National de la Recherche Scientifique Fund for Research Training in Industry and Agriculture (S.P.); Vrije Universiteit Brussel PhD funding (S.P.); and the Vrije Universiteit Brussel, Reproduction and Genetics and Regenerative Medicine Cluster, Reproduction, and Genetics Research Group (A.G. and S.V.D.). | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.rights | This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND). | - |
dc.subject.other | pathogenicity; bilocus combination; variants; prediction; oligogenic | - |
dc.subject.other | pathogenicity; bilocus combination; variants; prediction; oligogenic | - |
dc.title | Predicting disease-causing variant combinations | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 11887 | - |
dc.identifier.issue | 24 | - |
dc.identifier.spage | 11878 | - |
dc.identifier.volume | 116 | - |
local.format.pages | 10 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | [Papadimitriou, Sofia; Gazzo, Andrea; Versbraegen, Nassim; Nachtegael, Charlotte; Van Dooren, Sonia; Nowe, Ann; Smits, Guillaume; Lenaerts, Tom] Vrije Univ Brussel, Univ Libre Bruxelles, Interuniv Inst Bioinformat Brussels, B-1050 Brussels, Belgium. [Papadimitriou, Sofia; Gazzo, Andrea; Versbraegen, Nassim; Nachtegael, Charlotte; Lenaerts, Tom] Univ Libre Bruxelles, Machine Learning Grp, B-1050 Brussels, Belgium. [Papadimitriou, Sofia; Lenaerts, Tom] Vrije Univ Brussel, Artificial Intelligence Lab, B-1050 Brussels, Belgium. [Gazzo, Andrea; Van Dooren, Sonia] Vrije Univ Brussel, UZ Brussel, Ctr Med Genet Reprod & Genet, Reprod Genet & Regenerat Med, B-1090 Brussels, Belgium. [Aerts, Jan; Moreau, Yves] Univ Hasselt, Ctr Stat, B-3590 Diepenbeek, Belgium. [Aerts, Jan] Katholieke Univ Leuven, STADIUS Ctr Dynam Syst Signal Proc & Data Analyt, Dept Elect Engn, B-3001 Leuven, Belgium. [Moreau, Yves] Interuniv Microelect Ctr IMEC, B-3001 Leuven, Belgium. [Van Dooren, Sonia] Vrije Univ Brussel, Univ Libre Bruxelles, Brussels Interuniv Genom High Throughput Core, B-1090 Brussels, Belgium. [Smits, Guillaume] Univ Libre Bruxelles, Hop Univ Enfants Reine Fabiola, B-1020 Brussels, Belgium. [Smits, Guillaume] Univ Libre Bruxelles, Hop Erasme, Ctr Human Genet, B-1070 Brussels, Belgium. | - |
local.publisher.place | WASHINGTON | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1073/pnas.1815601116 | - |
dc.identifier.isi | 000471039700052 | - |
item.contributor | Papadimitriou, Sofia | - |
item.contributor | Gazzo, Andrea | - |
item.contributor | Versbraegen, Nassim | - |
item.contributor | Nachtegael, Charlotte | - |
item.contributor | AERTS, Jan | - |
item.contributor | Moreau, Yves | - |
item.contributor | Van Dooren, Sonia | - |
item.contributor | Nowe, Ann | - |
item.contributor | Smits, Guillaume | - |
item.contributor | Lenaerts, Tom | - |
item.fullcitation | Papadimitriou, Sofia; Gazzo, Andrea; Versbraegen, Nassim; Nachtegael, Charlotte; AERTS, Jan; Moreau, Yves; Van Dooren, Sonia; Nowe, Ann; Smits, Guillaume & Lenaerts, Tom (2019) Predicting disease-causing variant combinations. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116(24), p. 11878-11887. | - |
item.accessRights | Open Access | - |
item.fulltext | With Fulltext | - |
item.validation | ecoom 2020 | - |
crisitem.journal.issn | 0027-8424 | - |
crisitem.journal.eissn | 1091-6490 | - |
Appears in Collections: | Research publications |
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papadimitriou 1.pdf | Published version | 1.24 MB | Adobe PDF | View/Open |
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