Structure-based prediction of BRAF mutation classes using machine-learning approaches.

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_5CB3AA02B4B8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Structure-based prediction of BRAF mutation classes using machine-learning approaches.
Journal
Scientific reports
Author(s)
Krebs F.S., Britschgi C., Pradervand S., Achermann R., Tsantoulis P., Haefliger S., Wicki A., Michielin O., Zoete V.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
22/07/2022
Peer-reviewed
Oui
Volume
12
Number
1
Pages
12528
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The BRAF kinase is attracting a lot of attention in oncology as alterations of its amino acid sequence can constitutively activate the MAP kinase signaling pathway, potentially contributing to the malignant transformation of the cell but at the same time rendering it sensitive to targeted therapy. Several pathologic BRAF variants were grouped in three different classes (I, II and III) based on their effects on the protein activity and pathway. Discerning the class of a BRAF mutation permits to adapt the treatment proposed to the patient. However, this information is lacking new and experimentally uncharacterized BRAF mutations detected in a patient biopsy. To overcome this issue, we developed a new in silico tool based on machine learning approaches to predict the potential class of a BRAF missense variant. As class I only involves missense mutations of Val600, we focused on the mutations of classes II and III, which are more diverse and challenging to predict. Using a logistic regression model and features including structural information, we were able to predict the classes of known mutations with an accuracy of 90%. This new and fast predictive tool will help oncologists to tackle potential pathogenic BRAF mutations and to propose the most appropriate treatment for their patients.
Keywords
Humans, MAP Kinase Signaling System, Machine Learning, Mutation, Mutation, Missense, Proto-Oncogene Proteins B-raf/chemistry, Proto-Oncogene Proteins B-raf/genetics
Pubmed
Web of science
Open Access
Yes
Create date
02/08/2022 14:28
Last modification date
20/07/2023 6:55
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