Protein–protein interaction site prediction through combining local and global features with deep neural networks

2019 ◽  
Author(s):  
Min Zeng ◽  
Fuhao Zhang ◽  
Fang-Xiang Wu ◽  
Yaohang Li ◽  
Jianxin Wang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Protein Interactions ◽  
Supplementary Information ◽  
Protein Protein Interactions ◽  
Global Features ◽  
Site Prediction ◽  
Sequence Features ◽  
Protein Protein Interaction ◽  
Contextual Features ◽  
Interaction Site Prediction

Abstract Motivation Protein–protein interactions (PPIs) play important roles in many biological processes. Conventional biological experiments for identifying PPI sites are costly and time-consuming. Thus, many computational approaches have been proposed to predict PPI sites. Existing computational methods usually use local contextual features to predict PPI sites. Actually, global features of protein sequences are critical for PPI site prediction. Results A new end-to-end deep learning framework, named DeepPPISP, through combining local contextual and global sequence features, is proposed for PPI site prediction. For local contextual features, we use a sliding window to capture features of neighbors of a target amino acid as in previous studies. For global sequence features, a text convolutional neural network is applied to extract features from the whole protein sequence. Then the local contextual and global sequence features are combined to predict PPI sites. By integrating local contextual and global sequence features, DeepPPISP achieves the state-of-the-art performance, which is better than the other competing methods. In order to investigate if global sequence features are helpful in our deep learning model, we remove or change some components in DeepPPISP. Detailed analyses show that global sequence features play important roles in DeepPPISP. Availability and implementation The DeepPPISP web server is available at http://bioinformatics.csu.edu.cn/PPISP/. The source code can be obtained from https://github.com/CSUBioGroup/DeepPPISP. Supplementary information Supplementary data are available at Bioinformatics online.

Structure-aware protein–protein interaction site prediction using deep graph convolutional network

2021 ◽  
Author(s):  
Qianmu Yuan ◽  
Jianwen Chen ◽  
Huiying Zhao ◽  
Yaoqi Zhou ◽  
Yuedong Yang
Keyword(s):  
Protein Interactions ◽  
Spatial Information ◽  
Screening Tools ◽  
Supplementary Information ◽  
Protein Protein Interactions ◽  
Convolutional Network ◽  
Source Codes ◽  
Site Prediction ◽  
Protein Protein Interaction ◽  
Mapping Techniques

Abstract Motivation Protein–protein interactions (PPI) play crucial roles in many biological processes, and identifying PPI sites is an important step for mechanistic understanding of diseases and design of novel drugs. Since experimental approaches for PPI site identification are expensive and time-consuming, many computational methods have been developed as screening tools. However, these methods are mostly based on neighbored features in sequence, and thus limited to capture spatial information. Results We propose a deep graph-based framework deep Graph convolutional network for Protein–Protein-Interacting Site prediction (GraphPPIS) for PPI site prediction, where the PPI site prediction problem was converted into a graph node classification task and solved by deep learning using the initial residual and identity mapping techniques. We showed that a deeper architecture (up to eight layers) allows significant performance improvement over other sequence-based and structure-based methods by more than 12.5% and 10.5% on AUPRC and MCC, respectively. Further analyses indicated that the predicted interacting sites by GraphPPIS are more spatially clustered and closer to the native ones even when false-positive predictions are made. The results highlight the importance of capturing spatially neighboring residues for interacting site prediction. Availability and implementation The datasets, the pre-computed features, and the source codes along with the pre-trained models of GraphPPIS are available at https://github.com/biomed-AI/GraphPPIS. The GraphPPIS web server is freely available at https://biomed.nscc-gz.cn/apps/GraphPPIS. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals EGAT: Edge Aggregated Graph Attention Networks and Transfer Learning Improve Protein-Protein Interaction Site Prediction

2020 ◽  
Author(s):  
Sazan Mahbub ◽  
Md Shamsuzzoha Bayzid
Keyword(s):  
Transfer Learning ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Protein Interactions ◽  
Attention Networks ◽  
Site Prediction ◽  
Protein Protein Interaction ◽  
Interaction Site Prediction ◽  
First Time

AbstractMotivationProtein-protein interactions are central to most biological processes. However, reliable identification of protein-protein interaction (PPI) sites using conventional experimental methods is slow and expensive. Therefore, great efforts are being put into computational methods to identify PPI sites.ResultsWe present EGAT, a highly accurate deep learning based method for PPI site prediction, where we have introduced a novel edge aggregated graph attention network to effectively leverage the structural information. We, for the first time, have used transfer learning in PPI site prediction. Our proposed edge aggregated network, together with transfer learning, has achieved remarkable improvement over the best alternate methods. Furthermore, EGAT offers a more interpretable framework than the typical black-box deep neural networks.AvailabilityEGAT is freely available as an open source project at https://github.com/Sazan-Mahbub/EGAT.

scholarly journals A Deep Learning and XGBoost-Based Method for Predicting Protein-Protein Interaction Sites

2021 ◽  
Vol 12 ◽  
Author(s):  
Pan Wang ◽  
Guiyang Zhang ◽  
Zu-Guo Yu ◽  
Guohua Huang
Keyword(s):  
Deep Learning ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Gradient Boosting ◽  
Protein Protein Interactions ◽  
Global Features ◽  
Protein Protein Interaction ◽  
Interaction Sites ◽  
Extreme Gradient Boosting ◽  
Protein Interaction Sites

Knowledge about protein-protein interactions is beneficial in understanding cellular mechanisms. Protein-protein interactions are usually determined according to their protein-protein interaction sites. Due to the limitations of current techniques, it is still a challenging task to detect protein-protein interaction sites. In this article, we presented a method based on deep learning and XGBoost (called DeepPPISP-XGB) for predicting protein-protein interaction sites. The deep learning model served as a feature extractor to remove redundant information from protein sequences. The Extreme Gradient Boosting algorithm was used to construct a classifier for predicting protein-protein interaction sites. The DeepPPISP-XGB achieved the following results: area under the receiver operating characteristic curve of 0.681, a recall of 0.624, and area under the precision-recall curve of 0.339, being competitive with the state-of-the-art methods. We also validated the positive role of global features in predicting protein-protein interaction sites.

scholarly journals RAPPPID: Towards Generalisable Protein Interaction Prediction with AWD-LSTM Twin Networks

2021 ◽  
Author(s):  
Joseph Szymborski ◽  
Amin Emad
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Information Leakage ◽  
Supplementary Information ◽  
Protein Protein Interactions ◽  
Training Time ◽  
Interaction Prediction ◽  
Protein Protein Interaction ◽  
Protein Interaction Prediction ◽  
Time To Learn

Motivation: Computational methods for the prediction of protein-protein interactions, while important tools for researchers, are plagued by challenges in generalising to unseen proteins. Datasets used for modelling protein-protein predictions are particularly predisposed to information leakage and sampling biases. Results: In this study, we introduce RAPPPID, a method for the Regularised Automatic Prediction of Protein-Protein Interactions using Deep Learning. RAPPPID is a twin AWD-LSTM network which employs multiple regularisation methods during training time to learn generalised weights. Testing on stringent interaction datasets composed of proteins not seen during training, RAPPPID outperforms state-of-the-art methods. Further experiments show that RAPPPID's performance holds regardless of the particular proteins in the testing set and its performance is higher for biologically supported edges. This study serves to demonstrate that appropriate regularisation is an important component of overcoming the challenges of creating models for protein-protein interaction prediction that generalise to unseen proteins. Availability and Implementation: Code and datasets are freely available at https://github.com/jszym/rapppid. Contact: [email protected] Supplementary Information: Online-only supplementary data is available at the journal's website.

scholarly journals Benchmarking AlphaFold for protein complex modeling reveals accuracy determinants

2021 ◽  
Author(s):  
Rui Yin ◽  
Brandon Y Feng ◽  
Amitabh Varshney ◽  
Brian G Pierce
Keyword(s):  
Deep Learning ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Protein Docking ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Future Developments ◽  
Massive Number ◽  
Improved Performance

High resolution experimental structural determination of protein-protein interactions has led to valuable mechanistic insights, yet due to the massive number of interactions and experimental limitations there is a need for computational methods that can accurately model their structures. Here we explore the use of the recently developed deep learning method, AlphaFold, to predict structures of protein complexes from sequence. With a benchmark of 152 diverse heterodimeric protein complexes, multiple implementations and parameters of AlphaFold were tested for accuracy. Remarkably, many cases had highly accurate models generated as top-ranked predictions, greatly surpassing the performance of unbound protein-protein docking, whereas antibody-antigen docking was largely unsuccessful. While AlphaFold-generated accuracy predictions were able to discriminate near-native models, previously developed scoring protocols improved performance. Our study demonstrates that end-to-end deep learning can accurately model transient protein complexes, and identifies areas for improvement to guide future developments to reliably model any protein-protein interaction of interest.

An efficient transient assays system using Agrobacterium-mediated transformation of onion (Allium cepa) epidermal cells

2020 ◽  
Vol 80 (03) ◽  
Author(s):  
Yu-Miao Zhang ◽  
Jun Wang ◽  
Tao Wu
Keyword(s):  
Subcellular Localization ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Epidermal Cells ◽  
Cyclin Dependent Kinase ◽  
Protein Subcellular Localization ◽  
Protein Protein Interactions ◽  
Efficient System ◽  
Protein Protein Interaction ◽  
Onion Epidermal Cells

In this study, the Agrobacterium infection medium, infection duration, detergent, and cell density were optimized. The sorghum-based infection medium (SbIM), 10-20 min infection time, addition of 0.01% Silwet L-77, and Agrobacterium optical density at 600 nm (OD600), improved the competence of onion epidermal cells to support Agrobacterium infection at >90% efficiency. Cyclin-dependent kinase D-2 (CDKD-2) and cytochrome c-type biogenesis protein (CYCH), protein-protein interactions were localized. The optimized procedure is a quick and efficient system for examining protein subcellular localization and protein-protein interaction.

Deep Learning in the Study of Protein-Related Interactions

2020 ◽  
Vol 27 (5) ◽  
pp. 359-369 ◽  
Author(s):  
Cheng Shi ◽  
Jiaxing Chen ◽  
Xinyue Kang ◽  
Guiling Zhao ◽  
Xingzhen Lao ◽  
...  
Keyword(s):  
Deep Learning ◽  
Protein Interactions ◽  
Physiological Data ◽  
Great Promise ◽  
Complex Data ◽  
Protein Protein Interactions ◽  
Learning Patterns ◽  
Introductory Overview ◽  
Protein Research ◽  
Neural Network Theory

: Protein-related interaction prediction is critical to understanding life processes, biological functions, and mechanisms of drug action. Experimental methods used to determine proteinrelated interactions have always been costly and inefficient. In recent years, advances in biological and medical technology have provided us with explosive biological and physiological data, and deep learning-based algorithms have shown great promise in extracting features and learning patterns from complex data. At present, deep learning in protein research has emerged. In this review, we provide an introductory overview of the deep neural network theory and its unique properties. Mainly focused on the application of this technology in protein-related interactions prediction over the past five years, including protein-protein interactions prediction, protein-RNA\DNA, Protein– drug interactions prediction, and others. Finally, we discuss some of the challenges that deep learning currently faces.

Decoding Protein-protein Interactions: An Overview

2020 ◽  
Vol 20 (10) ◽  
pp. 855-882
Author(s):  
Olivia Slater ◽  
Bethany Miller ◽  
Maria Kontoyianni
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Drug Repurposing ◽  
Protein Docking ◽  
Target Space ◽  
Protein Protein Interactions ◽  
X Ray Crystallography ◽  
Protein Protein Interaction ◽  
Interaction Sites ◽  
Long Time

Drug discovery has focused on the paradigm “one drug, one target” for a long time. However, small molecules can act at multiple macromolecular targets, which serves as the basis for drug repurposing. In an effort to expand the target space, and given advances in X-ray crystallography, protein-protein interactions have become an emerging focus area of drug discovery enterprises. Proteins interact with other biomolecules and it is this intricate network of interactions that determines the behavior of the system and its biological processes. In this review, we briefly discuss networks in disease, followed by computational methods for protein-protein complex prediction. Computational methodologies and techniques employed towards objectives such as protein-protein docking, protein-protein interactions, and interface predictions are described extensively. Docking aims at producing a complex between proteins, while interface predictions identify a subset of residues on one protein that could interact with a partner, and protein-protein interaction sites address whether two proteins interact. In addition, approaches to predict hot spots and binding sites are presented along with a representative example of our internal project on the chemokine CXC receptor 3 B-isoform and predictive modeling with IP10 and PF4.

scholarly journals Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sun Sook Chung ◽  
Joseph C F Ng ◽  
Anna Laddach ◽  
N Shaun B Thomas ◽  
Franca Fraternali
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Short Loop ◽  
New Strategy ◽  
Loop Network ◽  
Protein Protein Interaction Network

Abstract Direct drug targeting of mutated proteins in cancer is not always possible and efficacy can be nullified by compensating protein–protein interactions (PPIs). Here, we establish an in silico pipeline to identify specific PPI sub-networks containing mutated proteins as potential targets, which we apply to mutation data of four different leukaemias. Our method is based on extracting cyclic interactions of a small number of proteins topologically and functionally linked in the Protein–Protein Interaction Network (PPIN), which we call short loop network motifs (SLM). We uncover a new property of PPINs named ‘short loop commonality’ to measure indirect PPIs occurring via common SLM interactions. This detects ‘modules’ of PPI networks enriched with annotated biological functions of proteins containing mutation hotspots, exemplified by FLT3 and other receptor tyrosine kinase proteins. We further identify functional dependency or mutual exclusivity of short loop commonality pairs in large-scale cellular CRISPR–Cas9 knockout screening data. Our pipeline provides a new strategy for identifying new therapeutic targets for drug discovery.

scholarly journals Universal Screening Methods and Applications of ThermoFluor®

2006 ◽  
Vol 11 (7) ◽  
pp. 854-863 ◽  
Author(s):  
Maxwell D. Cummings ◽  
Michael A. Farnum ◽  
Marina I. Nelen
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Protein Unfolding ◽  
Direct Detection ◽  
Functional Characterization ◽  
Screening Methods ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Bacterial Enzyme ◽  
Research Problems

The genomics revolution has unveiled a wealth of poorly characterized proteins. Scientists are often able to produce milligram quantities of proteins for which function is unknown or hypothetical, based only on very distant sequence homology. Broadly applicable tools for functional characterization are essential to the illumination of these orphan proteins. An additional challenge is the direct detection of inhibitors of protein-protein interactions (and allosteric effectors). Both of these research problems are relevant to, among other things, the challenge of finding and validating new protein targets for drug action. Screening collections of small molecules has long been used in the pharmaceutical industry as 1 method of discovering drug leads. Screening in this context typically involves a function-based assay. Given a sufficient quantity of a protein of interest, significant effort may still be required for functional characterization, assay development, and assay configuration for screening. Increasingly, techniques are being reported that facilitate screening for specific ligands for a protein of unknown function. Such techniques also allow for function-independent screening with better characterized proteins. ThermoFluor®, a screening instrument based on monitoring ligand effects on temperature-dependent protein unfolding, can be applied when protein function is unknown. This technology has proven useful in the decryption of an essential bacterial enzyme and in the discovery of a series of inhibitors of a cancer-related, protein-protein interaction. The authors review some of the tools relevant to these research problems in drug discovery, and describe our experiences with 2 different proteins.

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