DeepAVP: A Dual-Channel Deep Neural Network for Identifying Variable-Length Antiviral Peptides

Antiviral peptides (AVPs) have been experimentally verified to block virus into host cells, which have antiviral activity with decapeptide amide. Therefore, utilization of experimentally validated antiviral peptides is a potential alternative strategy for targeting medically important viruses. In this article, we propose a dual-channel deep neural network ensemble method for analyzing variable-length antiviral peptides. The LSTM channel can capture long-term dependencies for effectively studying original variable-length sequence data. The CONV channel can build dynamic neural network for analyzing the local evolution information. Also, our model can fine-tune the substitution matrix for specifically functional peptides. Applying it to a novel experimentally verified dataset, our AVPs predictor, DeepAVP, demonstrates state-of-the-art performance of $\text{92.4}\%$ accuracy and 0.85 MCC, which is far better than existing prediction methods for identifying antiviral peptides. Therefore, DeepAVP, web server for predicting the effective AVPs, would make significantly contributions to peptide-based antiviral research.

[1]  Shijian Zhang,et al.  Inhibition of Influenza Virus Replication by Constrained Peptides Targeting Nucleoprotein , 2011, Antiviral chemistry & chemotherapy.

[2]  Saheli Sadanand Vaccination: The Present and the Future , 2011, The Yale journal of biology and medicine.

[3]  Xia Li,et al.  APD2: the updated antimicrobial peptide database and its application in peptide design , 2008, Nucleic Acids Res..

[4]  Mandana Behbahani,et al.  Using Chou’s Pseudo Amino Acid Composition and Machine LearningMethod to Predict the Antiviral Peptides , 2015 .

[5]  Suzana Popovic,et al.  Peptides with antimicrobial and anti-inflammatory activities that have therapeutic potential for treatment of acne vulgaris , 2012, Peptides.

[6]  William Stafford Noble,et al.  Empirical comparison of web‐based antimicrobial peptide prediction tools , 2017, Bioinform..

[7]  Ole Winther,et al.  Convolutional LSTM Networks for Subcellular Localization of Proteins , 2015, AlCoB.

[8]  Jürgen Schmidhuber,et al.  Long Short-Term Memory , 1997, Neural Computation.

[9]  Dongsup Kim,et al.  Deep convolutional neural networks for pan-specific peptide-MHC class I binding prediction , 2017, BMC Bioinformatics.

[10]  Jorge Félix Beltrán Lissabet,et al.  AntiVPP 1.0: A portable tool for prediction of antiviral peptides , 2019, Computers in Biology and Medicine.

[11]  Manoj Kumar,et al.  AVPdb: a database of experimentally validated antiviral peptides targeting medically important viruses , 2013, Nucleic Acids Res..

[12]  Jun Liu,et al.  Overlap and diversity in antimicrobial peptide databases: compiling a non-redundant set of sequences , 2015, Bioinform..

[13]  P. Legrain,et al.  Antiviral Drug Discovery Strategy Using Combinatorial Libraries of Structurally Constrained Peptides , 2004, Journal of Virology.

[14]  Gajendra P. S. Raghava,et al.  AntiBP2: improved version of antibacterial peptide prediction , 2010, BMC Bioinformatics.

[15]  Xing Chen,et al.  MeT-DB V2.0: elucidating context-specific functions of N6-methyl-adenosine methyltranscriptome , 2017, Nucleic Acids Res..

[16]  R. Frank,et al.  Identification of High-Affinity PB1-Derived Peptides with Enhanced Affinity to the PA Protein of Influenza A Virus Polymerase , 2010, Antimicrobial Agents and Chemotherapy.

[17]  C. Brandt,et al.  Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection , 2008, Antimicrobial Agents and Chemotherapy.

[18]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[20]  Haijun Lei,et al.  Protein–Protein Interactions Prediction via Multimodal Deep Polynomial Network and Regularized Extreme Learning Machine , 2019, IEEE Journal of Biomedical and Health Informatics.

[21]  Majid Mohammadi,et al.  A Projection Neural Network for Identifying Copy Number Variants , 2019, IEEE Journal of Biomedical and Health Informatics.

[22]  Amarda Shehu,et al.  Deep learning improves antimicrobial peptide recognition , 2018, Bioinform..

[23]  K. Chou,et al.  Prediction of Antimicrobial Peptides Based on Sequence Alignment and Feature Selection Methods , 2011, PloS one.

[24]  Shreyas Karnik,et al.  CAMP: a useful resource for research on antimicrobial peptides , 2009, Nucleic Acids Res..

[25]  Fei Guo,et al.  Identification of Drug-Side Effect Association via Semisupervised Model and Multiple Kernel Learning , 2019, IEEE Journal of Biomedical and Health Informatics.

[26]  Manuel Sanchez-Castillo,et al.  A Bayesian framework for the inference of gene regulatory networks from time and pseudo‐time series data , 2018, Bioinform..

[27]  Jianlin Cheng,et al.  A Deep Learning Network Approach to ab initio Protein Secondary Structure Prediction , 2015, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[28]  Guillaume Castel,et al.  Phage Display of Combinatorial Peptide Libraries: Application to Antiviral Research , 2011, Molecules.

[29]  Guang-Zhong Yang,et al.  Deep Learning for Health Informatics , 2017, IEEE Journal of Biomedical and Health Informatics.

[30]  Xiaowei Zhao,et al.  LAMP: A Database Linking Antimicrobial Peptides , 2013, PloS one.

[31]  Ashish,et al.  Antiviral Peptides Targeting the West Nile Virus Envelope Protein , 2006, Journal of Virology.

[32]  Michele A. Busby,et al.  Supplementary Materials for Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification , 2018 .

[33]  Jeremy C. Jones,et al.  Identification of the Minimal Active Sequence of an Anti-Influenza Virus Peptide , 2011, Antimicrobial Agents and Chemotherapy.

[34]  Dong Xu,et al.  Imbalanced multi-label learning for identifying antimicrobial peptides and their functional types , 2016, Bioinform..

[35]  G. Schneider,et al.  Designing antimicrobial peptides: form follows function , 2011, Nature Reviews Drug Discovery.

[36]  T. Narumi,et al.  Conjugation of cell-penetrating peptides leads to identification of anti-HIV peptides from matrix proteins. , 2012, Bioorganic & medicinal chemistry.

[37]  Jijun Tang,et al.  Identification of protein subcellular localization via integrating evolutionary and physicochemical information into Chou's general PseAAC. , 2019, Journal of theoretical biology.

[38]  Xia Li,et al.  APD3: the antimicrobial peptide database as a tool for research and education , 2015, Nucleic Acids Res..

[39]  R D Appel,et al.  Protein identification and analysis tools in the ExPASy server. , 1999, Methods in molecular biology.

[40]  Kuan Y. Chang,et al.  Analysis and Prediction of Highly Effective Antiviral Peptides Based on Random Forests , 2013, PloS one.

[41]  Manoj Kumar,et al.  VIRsiRNAdb: a curated database of experimentally validated viral siRNA/shRNA , 2011, Nucleic Acids Res..

[42]  Mehrdad Nourani,et al.  Clustering Single-Cell Expression Data Using Random Forest Graphs , 2017, IEEE Journal of Biomedical and Health Informatics.

[43]  M. García-Delgado,et al.  Peptide Inhibitors of Hepatitis C Virus NS3 Protease , 2003, Antiviral chemistry & chemotherapy.

[44]  T. D. Schneider,et al.  Use of the 'Perceptron' algorithm to distinguish translational initiation sites in E. coli. , 1982, Nucleic acids research.

[45]  Faiza Hanif Waghu,et al.  CAMPR3: a database on sequences, structures and signatures of antimicrobial peptides , 2015, Nucleic Acids Res..

[46]  Adam Godzik,et al.  Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences , 2006, Bioinform..

[47]  D. Lambert,et al.  Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Manoj Kumar,et al.  AVPpred: collection and prediction of highly effective antiviral peptides , 2012, Nucleic Acids Res..