Dataset Information

Convolutional Neural Network Based Approach to in Silico Non-Anticipating Prediction of Antigenic Distance for Influenza Virus.

ABSTRACT: Evaluation of the antigenic similarity degree between the strains of the influenza virus is highly important for vaccine production. The conventional method used to measure such a degree is related to performing the immunological assays of hemagglutinin inhibition. Namely, the antigenic distance between two strains is calculated on the basis of HI assays. Usually, such distances are visualized by using some kind of antigenic cartography method. The known drawback of the HI assay is that it is rather time-consuming and expensive. In this paper, we propose a novel approach for antigenic distance approximation based on deep learning in the feature spaces induced by hemagglutinin protein sequences and Convolutional Neural Networks (CNNs). To apply a CNN to compare the protein sequences, we utilize the encoding based on the physical and chemical characteristics of amino acids. By varying (hyper)parameters of the CNN architecture design, we find the most robust network. Further, we provide insight into the relationship between approximated antigenic distance and antigenicity by evaluating the network on the HI assay database for the H1N1 subtype. The results indicate that the best-trained network gives a high-precision approximation for the ground-truth antigenic distances, and can be used as a good exploratory tool in practical tasks.

SUBMITTER: Forghani M

PROVIDER: S-EPMC7551508 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Convolutional Neural Network Based Approach to in Silico Non-Anticipating Prediction of Antigenic Distance for Influenza Virus.

Forghani Majid M Khachay Michael M

Viruses 20200912 9

Evaluation of the antigenic similarity degree between the strains of the influenza virus is highly important for vaccine production. The conventional method used to measure such a degree is related to performing the immunological assays of hemagglutinin inhibition. Namely, the antigenic distance between two strains is calculated on the basis of HI assays. Usually, such distances are visualized by using some kind of antigenic cartography method. The known drawback of the HI assay is that it is ra ...[more]

PMID: 32932748

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Project description:BackgroundDriven by deep learning, inter-residue contact/distance prediction has been significantly improved and substantially enhanced ab initio protein structure prediction. Currently, most of the distance prediction methods classify inter-residue distances into multiple distance intervals instead of directly predicting real-value distances. The output of the former has to be converted into real-value distances to be used in tertiary structure prediction.ResultsTo explore the potentials of predicting real-value inter-residue distances, we develop a multi-task deep learning distance predictor (DeepDist) based on new residual convolutional network architectures to simultaneously predict real-value inter-residue distances and classify them into multiple distance intervals. Tested on 43 CASP13 hard domains, DeepDist achieves comparable performance in real-value distance prediction and multi-class distance prediction. The average mean square error (MSE) of DeepDist's real-value distance prediction is 0.896 Å2 when filtering out the predicted distance ≥ 16 Å, which is lower than 1.003 Å2 of DeepDist's multi-class distance prediction. When distance predictions are converted into contact predictions at 8 Å threshold (the standard threshold in the field), the precision of top L/5 and L/2 contact predictions of DeepDist's multi-class distance prediction is 79.3% and 66.1%, respectively, higher than 78.6% and 64.5% of its real-value distance prediction and the best results in the CASP13 experiment.ConclusionsDeepDist can predict inter-residue distances well and improve binary contact prediction over the existing state-of-the-art methods. Moreover, the predicted real-value distances can be directly used to reconstruct protein tertiary structures better than multi-class distance predictions due to the lower MSE. Finally, we demonstrate that predicting the real-value distance map and multi-class distance map at the same time performs better than predicting real-value distances alone.

Project description:Motivation:A majority of known genetic variants associated with human-inherited diseases lie in non-coding regions that lack adequate interpretation, making it indispensable to systematically discover functional sites at the whole genome level and precisely decipher their implications in a comprehensive manner. Although computational approaches have been complementing high-throughput biological experiments towards the annotation of the human genome, it still remains a big challenge to accurately annotate regulatory elements in the context of a specific cell type via automatic learning of the DNA sequence code from large-scale sequencing data. Indeed, the development of an accurate and interpretable model to learn the DNA sequence signature and further enable the identification of causative genetic variants has become essential in both genomic and genetic studies. Results:We proposed Deopen, a hybrid framework mainly based on a deep convolutional neural network, to automatically learn the regulatory code of DNA sequences and predict chromatin accessibility. In a series of comparison with existing methods, we show the superior performance of our model in not only the classification of accessible regions against background sequences sampled at random, but also the regression of DNase-seq signals. Besides, we further visualize the convolutional kernels and show the match of identified sequence signatures and known motifs. We finally demonstrate the sensitivity of our model in finding causative noncoding variants in the analysis of a breast cancer dataset. We expect to see wide applications of Deopen with either public or in-house chromatin accessibility data in the annotation of the human genome and the identification of non-coding variants associated with diseases. Availability and implementation:Deopen is freely available at https://github.com/kimmo1019/Deopen. Contact:ruijiang@tsinghua.edu.cn. Supplementary information:Supplementary data are available at Bioinformatics online.

Project description:BACKGROUND:Identifying splice sites is a necessary step to analyze the location and structure of genes. Two dinucleotides, GT and AG, are highly frequent on splice sites, and many other patterns are also on splice sites with important biological functions. Meanwhile, the dinucleotides occur frequently at the sequences without splice sites, which makes the prediction prone to generate false positives. Most existing tools select all the sequences with the two dimers and then focus on distinguishing the true splice sites from those pseudo ones. Such an approach will lead to a decrease in false positives; however, it will result in non-canonical splice sites missing. RESULT:We have designed SpliceFinder based on convolutional neural network (CNN) to predict splice sites. To achieve the ab initio prediction, we used human genomic data to train our neural network. An iterative approach is adopted to reconstruct the dataset, which tackles the data unbalance problem and forces the model to learn more features of splice sites. The proposed CNN obtains the classification accuracy of 90.25%, which is 10% higher than the existing algorithms. The method outperforms other existing methods in terms of area under receiver operating characteristics (AUC), recall, precision, and F1 score. Furthermore, SpliceFinder can find the exact position of splice sites on long genomic sequences with a sliding window. Compared with other state-of-the-art splice site prediction tools, SpliceFinder generates results in about half lower false positive while keeping recall higher than 0.8. Also, SpliceFinder captures the non-canonical splice sites. In addition, SpliceFinder performs well on the genomic sequences of Drosophila melanogaster, Mus musculus, Rattus, and Danio rerio without retraining. CONCLUSION:Based on CNN, we have proposed a new ab initio splice site prediction tool, SpliceFinder, which generates less false positives and can detect non-canonical splice sites. Additionally, SpliceFinder is transferable to other species without retraining. The source code and additional materials are available at https://gitlab.deepomics.org/wangruohan/SpliceFinder.

Dataset Information

Convolutional Neural Network Based Approach to in Silico Non-Anticipating Prediction of Antigenic Distance for Influenza Virus.

Publications

Convolutional Neural Network Based Approach to in Silico Non-Anticipating Prediction of Antigenic Distance for Influenza Virus.

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