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      Identifying SNARE Proteins Using an Alignment-Free Method Based on Multiscan Convolutional Neural Network and PSSM Profiles

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          Abstract

          Background: SNARE proteins play a vital role in membrane fusion and cellular physiology and pathological processes. Many potential therapeutics for mental diseases or even cancer based on SNAREs are also developed. Therefore, there is a dire need to predict the SNAREs for further manipulation of these essential proteins, which demands new and efficient approaches. Methods: Some computational frameworks were proposed to tackle the hurdles of biological methods, which take plenty of time and budget to conduct the identification of SNAREs. However, the performances of existing frameworks were insufficiently satisfied, as they failed to retain the SNARE sequence order and capture the mass hidden features from SNAREs. This paper proposed a novel model constructed on the multiscan convolutional neural network (CNN) and position-specific scoring matrix (PSSM) profiles to address these limitations. We employed and trained our model on the benchmark dataset with fivefold cross-validation and two different independent datasets. Results: Overall, the multiscan CNN was cross-validated on the training set and excelled in the SNARE classification reaching 0.963 in AUC and 0.955 in AUPRC. On top of that, with the sensitivity, specificity, accuracy, and MCC of 0.842, 0.968, 0.955, and 0.767, respectively, our proposed framework outperformed previous models in the SNARE recognition task. Conclusions: It is truly believed that our model can contribute to the discrimination of SNARE proteins and general proteins.

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          Most cited references57

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          Deep learning.

          Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
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            Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

            S Altschul (1997)
            The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.
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              SMOTE: Synthetic Minority Over-sampling Technique

              An approach to the construction of classifiers from imbalanced datasets is described. A dataset is imbalanced if the classification categories are not approximately equally represented. Often real-world data sets are predominately composed of ``normal'' examples with only a small percentage of ``abnormal'' or ``interesting'' examples. It is also the case that the cost of misclassifying an abnormal (interesting) example as a normal example is often much higher than the cost of the reverse error. Under-sampling of the majority (normal) class has been proposed as a good means of increasing the sensitivity of a classifier to the minority class. This paper shows that a combination of our method of over-sampling the minority (abnormal) class and under-sampling the majority (normal) class can achieve better classifier performance (in ROC space) than only under-sampling the majority class. This paper also shows that a combination of our method of over-sampling the minority class and under-sampling the majority class can achieve better classifier performance (in ROC space) than varying the loss ratios in Ripper or class priors in Naive Bayes. Our method of over-sampling the minority class involves creating synthetic minority class examples. Experiments are performed using C4.5, Ripper and a Naive Bayes classifier. The method is evaluated using the area under the Receiver Operating Characteristic curve (AUC) and the ROC convex hull strategy.
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                Author and article information

                Journal
                J Chem Inf Model
                J Chem Inf Model
                ci
                jcisd8
                Journal of Chemical Information and Modeling
                American Chemical Society
                1549-9596
                1549-960X
                27 September 2022
                10 October 2022
                : 62
                : 19
                : 4820-4826
                Affiliations
                []International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University , Taipei 110, Taiwan
                []College of Information & Communication Technology, Can Tho University , Can Tho 90000, Viet Nam
                [§ ]Department of Computer Science and Engineering, Yuan Ze University , Chung-Li 32003, Taiwan
                []Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University , Taipei 106, Taiwan
                []Research Center for Artificial Intelligence in Medicine, Taipei Medical University , Taipei 106, Taiwan
                [# ]Translational Imaging Research Center, Taipei Medical University Hospital , Taipei 110, Taiwan
                Author notes
                Author information
                https://orcid.org/0000-0003-4896-7926
                Article
                10.1021/acs.jcim.2c01034
                9554904
                36166351
                1c4eb553-d43d-4c5c-87d6-1db65002bea9
                © 2022 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 14 August 2022
                Funding
                Funded by: Ministry of Science and Technology, Taiwan, doi 10.13039/501100004663;
                Award ID: MOST110-2221-E-038-001-MY2
                Funded by: Ministry of Science and Technology, Taiwan, doi 10.13039/501100004663;
                Award ID: MOST111-2628-E-038-002-MY3
                Categories
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                Custom metadata
                ci2c01034
                ci2c01034

                Computational chemistry & Modeling
                Computational chemistry & Modeling

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