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      DeepTrio: a ternary prediction system for protein–protein interaction using mask multiple parallel convolutional neural networks

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          Abstract

          Motivation

          Protein–protein interaction (PPI), as a relative property, is determined by two binding proteins, which brings a great challenge to design an expert model with an unbiased learning architecture and a superior generalization performance. Additionally, few efforts have been made to allow PPI predictors to discriminate between relative properties and intrinsic properties.

          Results

          We present a sequence-based approach, DeepTrio, for PPI prediction using mask multiple parallel convolutional neural networks. Experimental evaluations show that DeepTrio achieves a better performance over several state-of-the-art methods in terms of various quality metrics. Besides, DeepTrio is extended to provide additional insights into the contribution of each input neuron to the prediction results.

          Availability and implementation

          We provide an online application at http://bis.zju.edu.cn/deeptrio. The DeepTrio models and training data are deposited at https://github.com/huxiaoti/deeptrio.git.

          Supplementary information

          Supplementary data are available at Bioinformatics online.

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          Most cited references42

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          Long Short-Term Memory

          Learning to store information over extended time intervals by recurrent backpropagation takes a very long time, mostly because of insufficient, decaying error backflow. We briefly review Hochreiter's (1991) analysis of this problem, then address it by introducing a novel, efficient, gradient-based method called long short-term memory (LSTM). Truncating the gradient where this does not do harm, LSTM can learn to bridge minimal time lags in excess of 1000 discrete-time steps by enforcing constant error flow through constant error carousels within special units. Multiplicative gate units learn to open and close access to the constant error flow. LSTM is local in space and time; its computational complexity per time step and weight is O(1). Our experiments with artificial data involve local, distributed, real-valued, and noisy pattern representations. In comparisons with real-time recurrent learning, back propagation through time, recurrent cascade correlation, Elman nets, and neural sequence chunking, LSTM leads to many more successful runs, and learns much faster. LSTM also solves complex, artificial long-time-lag tasks that have never been solved by previous recurrent network algorithms.
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            STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

            Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
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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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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                01 February 2022
                25 October 2021
                25 October 2021
                : 38
                : 3
                : 694-702
                Affiliations
                [1 ] Department of Bioinformatics, College of Life Sciences, Zhejiang University , Hangzhou 310058, China
                [2 ] Department of Mathematical Sciences, University of Essex , Colchester CO4 3SQ, UK
                [3 ] Biomedical Big Data Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Institute of Hematology, Zhejiang University , Hangzhou 310058, China
                Author notes
                To whom correspondence should be addressed. mchen@ 123456zju.edu.cn
                Author information
                https://orcid.org/0000-0002-9677-1699
                Article
                btab737
                10.1093/bioinformatics/btab737
                8756175
                34694333
                b74147bf-9bad-4d58-bc20-090f4064c33c
                © The Author(s) 2021. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 April 2021
                : 05 October 2021
                : 06 October 2021
                : 20 October 2021
                : 05 November 2021
                Page count
                Pages: 9
                Funding
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2016YFA0501704
                Award ID: 2018YFC0310602
                Funded by: National Natural Sciences Foundation of China;
                Award ID: 31771477
                Award ID: 32070677
                Funded by: 151 Talent Project of Zhejiang Province;
                Funded by: Jiangsu Collaborative Innovation Center for Modern Crop Production and Collaborative Innovation Center for Modern Crop Production cosponsored by province and ministry;
                Categories
                Original Papers
                Structural Bioinformatics
                AcademicSubjects/SCI01060

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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