ETRO VUB
About ETRO  |  News  |  Events  |  Vacancies  |  Contact  
Home Research Education Industry Publications About ETRO

ETRO Publications

Full Details

Other Publication

Predicting disease-causing variant combinations for oligogenic diseases

Authors: S. Papadimitriou, N. Versbraegen, C. Nachtegael, J. Aerts, Y. Moreau, S. Van Dooren, A. Nowé, G. Smits and T. Lenaerts

Publication Date: Mar. 2018


Abstract:

Notwithstanding advances in predicting pathogenic variants in rare monogenic diseases, identifying causative variant combinations in disorders where more genes are involved still remains a challenge. As data on digenic diseases accumulates, we can now develop predictive methods that identify pathogenic variant combinations in gene pairs. We present VarCoPP, the first Variant Combination Pathogenicity Predictor, which is an innovative tool for variant assessment in oligogenic disorders. VarCoPP was trained on pathogenic digenic variant combinations from the Digenic Diseases Database (DIDA) and neutral digenic combinations from the 1000 Genomes Project. By combining 500 different trained Random Forest predictors, VarCoPP differentiates pathogenic from neutral digenic variant combinations. After cross-validation the predictor reaches a Matthews Correlation Coefficient of 0.74. VarCoPP ranks the results and provides evaluation scores for each prediction, i.e. a Classification Score (CS), which expresses the likelihood of a digenic combination being pathogenic and a Support Score (SS) that expresses how many RFs agree with that decision. Clinically relevant confidence zones, delimited by minimum CS and SS scores, are also provided that guarantee with 95% or a 99% probability that the prediction is indeed a true positive. Validation with 23 gene pairs related to digenic diseases not yet present in DIDA shows that the method identifies 20 cases correctly, all of which have at least a 95% confidence score. The results of VarCoPP show that the first steps to oligogenic pathogenicity prediction can be taken, expanding our capability to assist clinicians and geneticists in unraveling oligogenic signatures in rare diseases.

Other Reference Styles
Other Publications

• Journal publications

IRIS • LAMI • AVSP

• Conference publications

IRIS • LAMI • AVSP

• Book publications

IRIS • LAMI • AVSP

• Reports

IRIS • LAMI • AVSP

• Laymen publications

IRIS • LAMI • AVSP

• PhD Theses

Search ETRO Publications

Author:

Keyword:  

Type:








- Contact person

- IRIS

- AVSP

- LAMI

- Contact person

- Thesis proposals

- ETRO Courses

- Contact person

- Spin-offs

- Know How

- Journals

- Conferences

- Books

- Vacancies

- News

- Events

- Press

Contact

ETRO Department

info@etro.vub.ac.be

Tel: +32 2 629 29 30

©2019 • Vrije Universiteit Brussel • ETRO Dept. • Pleinlaan 2 • 1050 Brussels • Tel: +32 2 629 2930 (secretariat) • Fax: +32 2 629 2883 • WebmasterDisclaimer