Dataset Information

Predicting the Disease Risk of Protein Mutation Sequences With Pre-training Model.

ABSTRACT: Accurately identifying the missense mutations is of great help to alleviate the loss of protein function and structural changes, which might greatly reduce the risk of disease for tumor suppressor genes (e.g., BRCA1 and PTEN). In this paper, we propose a hybrid framework, called BertVS, that predicts the disease risk for the missense mutation of proteins. Our framework is able to learn sequence representations from the protein domain through pre-training BERT models, and also integrates with the hydrophilic properties of amino acids to obtain the sequence representations of biochemical characteristics. The concatenation of two learned representations are then sent to the classifier to predict the missense mutations of protein sequences. Specifically, we use the protein family database (Pfam) as a corpus to train the BERT model to learn the contextual information of protein sequences, and our pre-training BERT model achieves a value of 0.984 on accuracy in the masked language model prediction task. We conduct extensive experiments on BRCA1 and PTEN datasets. With comparison to the baselines, results show that BertVS achieves higher performance of 0.920 on AUROC and 0.915 on AUPR in the functionally critical domain of the BRCA1 gene. Additionally, the extended experiment on the ClinVar dataset can illustrate that gene variants with known clinical significance can also be efficiently classified by our method. Therefore, BertVS can learn the functional information of the protein sequences and effectively predict the disease risk of variants with an uncertain clinical significance.

SUBMITTER: Li K

PROVIDER: S-EPMC7780924 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Predicting the Disease Risk of Protein Mutation Sequences With Pre-training Model.

Li Kuan K Zhong Yue Y Lin Xuan X Quan Zhe Z

Frontiers in genetics 20201221

Accurately identifying the missense mutations is of great help to alleviate the loss of protein function and structural changes, which might greatly reduce the risk of disease for tumor suppressor genes (e.g., BRCA1 and PTEN). In this paper, we propose a hybrid framework, called BertVS, that predicts the disease risk for the missense mutation of proteins. Our framework is able to learn sequence representations from the protein domain through pre-training BERT models, and also integrates with the ...[more]

PMID: 33408741

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Project description:BackgroundKnowledge of structural class is used by numerous methods for identification of structural/functional characteristics of proteins and could be used for the detection of remote homologues, particularly for chains that share twilight-zone similarity. In contrast to existing sequence-based structural class predictors, which target four major classes and which are designed for high identity sequences, we predict seven classes from sequences that share twilight-zone identity with the training sequences.ResultsThe proposed MODular Approach to Structural class prediction (MODAS) method is unique as it allows for selection of any subset of the classes. MODAS is also the first to utilize a novel, custom-built feature-based sequence representation that combines evolutionary profiles and predicted secondary structure. The features quantify information relevant to the definition of the classes including conservation of residues and arrangement and number of helix/strand segments. Our comprehensive design considers 8 feature selection methods and 4 classifiers to develop Support Vector Machine-based classifiers that are tailored for each of the seven classes. Tests on 5 twilight-zone and 1 high-similarity benchmark datasets and comparison with over two dozens of modern competing predictors show that MODAS provides the best overall accuracy that ranges between 80% and 96.7% (83.5% for the twilight-zone datasets), depending on the dataset. This translates into 19% and 8% error rate reduction when compared against the best performing competing method on two largest datasets. The proposed predictor provides accurate predictions at 58% accuracy for membrane proteins class, which is not considered by majority of existing methods, in spite that this class accounts for only 2% of the data. Our predictive model is analyzed to demonstrate how and why the input features are associated with the corresponding classes.ConclusionsThe improved predictions stem from the novel features that express collocation of the secondary structure segments in the protein sequence and that combine evolutionary and secondary structure information. Our work demonstrates that conservation and arrangement of the secondary structure segments predicted along the protein chain can successfully predict structural classes which are defined based on the spatial arrangement of the secondary structures. A web server is available at http://biomine.ece.ualberta.ca/MODAS/.

Dataset Information

Predicting the Disease Risk of Protein Mutation Sequences With Pre-training Model.

Publications

Predicting the Disease Risk of Protein Mutation Sequences With Pre-training Model.

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