MLb-LDLr: A Machine Learning Model for Predicting the Pathogenicity of LDLr Missense Variants

Untreated familial hypercholesterolemia (FH) leads to atherosclerosis and early cardiovascular disease. Mutations in the low-density lipoprotein receptor (LDLr) gene constitute the major cause of FH, and the high number of mutations already described in the LDLr makes necessary cascade screening or...

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Detalles Bibliográficos
Autores: Larrea, Asier, Benito-Vicente, Asier, Fernández-Higuero, José Ángel, Jebari-Benslaiman, Shifa, Galicia-García, Unai, Uribe, Kepa B., Cenarro, Ana, Ostolaza, Helena, Civeira, Fernando, Arrasate, Sonia, González-Díaz, Humberto, Martín, César
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/311418
Acceso en línea:http://hdl.handle.net/10261/311418
https://api.elsevier.com/content/abstract/scopus_id/85118822550
Access Level:acceso abierto
Palabra clave:ANN, artificial neural network
AUROC, area under the receiver operating curve
EGS, expert-guided selection
ESEA, Excel Solver Evolutionary algorithm
FH, familial hypercholesterolemia
LDA, linear discriminant analysis
LDL receptor
LDL, low-density lipoprotein
LDLr, low-density lipoprotein receptor
LNN, linear neural networks
ML, machine learning
MLP, multilayer perceptron
MLb-LDLr, machine-learning–based low-density lipoprotein receptor software
RBF, radial basis function
UTR, untranslated region
Familial hypercholesterolemia
Machine learning software
Pathogenicity
Prediction
Descripción
Sumario:Untreated familial hypercholesterolemia (FH) leads to atherosclerosis and early cardiovascular disease. Mutations in the low-density lipoprotein receptor (LDLr) gene constitute the major cause of FH, and the high number of mutations already described in the LDLr makes necessary cascade screening or in vitro functional characterization to provide a definitive diagnosis. Implementation of high-predicting capacity software constitutes a valuable approach for assessing pathogenicity of LDLr variants to help in the early diagnosis and management of FH disease. This work provides a reliable machine learning model to accurately predict the pathogenicity of LDLr missense variants with specificity of 92.5% and sensitivity of 91.6%.