A Novel Model for Identifying Essential Proteins Based on Key Target Convergence Sets

In recent years, many computational models have been designed to detect essential proteins based on protein-protein interaction (PPI) networks. However, due to the incompleteness of PPI networks, the prediction accuracy of these models is still not satisfactory. In this manuscript, a novel key target convergence sets based prediction model (KTCSPM) is proposed to identify essential proteins. In KTCSPM, a weighted PPI network and a weighted (Domain-Domain Interaction) network are constructed first based on known PPIs and PDIs downloaded from benchmark databases. And then, by integrating these two kinds of networks, a novel weighted PDI network is built. Next, through assigning a unique key target convergence set (KTCS) for each node in the weighted PDI network, an improved method based on the random walk with restart is designed to identify essential proteins. Finally, in order to evaluate the predictive effects of KTCSPM, it is compared with 12 competitive state-of-the-art models, and experimental results show that KTCSPM can achieve better prediction accuracy. Considering the satisfactory predictive performance achieved by KTCSPM, it indicates that KTCSPM might be a good supplement to the future research on prediction of essential proteins.

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CLUSTERING ALGORITHMS FOR DETECTING FUNCTIONAL MODULES IN PROTEIN INTERACTION NETWORKS

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720009004023 ◽

2009 ◽

Vol 07 (01) ◽

pp. 217-242 ◽

Cited By ~ 24

Author(s):

LIN GAO ◽

PENG-GANG SUN ◽

JIA SONG

Keyword(s):

Protein Interaction ◽

Protein Complexes ◽

Clustering Algorithms ◽

Interaction Network ◽

Future Research ◽

Functional Modules ◽

Sources Of Information ◽

Protein Protein Interaction ◽

Metabolic Functions ◽

Ppi Networks

Protein–Protein Interaction (PPI) networks are believed to be important sources of information related to biological processes and complex metabolic functions of the cell. When studying the workings of a biological cell, it is useful to be able to detect known and predict still undiscovered protein complexes within the cell's PPI networks. Such predictions may be used as an inexpensive tool to direct biological experiments. The increasing amount of available PPI data necessitate a fast, accurate approach to biological complex identification. Because of its importance in the studies of protein interaction network, there are different models and algorithms in identifying functional modules in PPI networks. In this paper, we review some representative algorithms, focusing on the algorithms underlying the approaches and how the algorithms relate to each other. In particular, a comparison is given based on the property of the algorithms. Since the PPI network is noisy and still incomplete, some methods which consider other additional properties for preprocessing and purifying of PPI data are presented. We also give a discussion about the functional annotation and validation of protein complexes. Finally, new progress and future research directions are discussed from the computational viewpoint.

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Method for Essential Protein Prediction Based on a Novel Weighted Protein-Domain Interaction Network

Frontiers in Genetics ◽

10.3389/fgene.2021.645932 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zixuan Meng ◽

Linai Kuang ◽

Zhiping Chen ◽

Zhen Zhang ◽

Yihong Tan ◽

...

Keyword(s):

Protein Identification ◽

Computational Models ◽

Predictive Accuracy ◽

Interaction Network ◽

Protein Domain ◽

Biological Information ◽

Ppi Network ◽

Domain Interaction ◽

Topological Features ◽

Ppi Networks

In recent years a number of calculative models based on protein-protein interaction (PPI) networks have been proposed successively. However, due to false positives, false negatives, and the incompleteness of PPI networks, there are still many challenges affecting the design of computational models with satisfactory predictive accuracy when inferring key proteins. This study proposes a prediction model called WPDINM for detecting key proteins based on a novel weighted protein-domain interaction (PDI) network. In WPDINM, a weighted PPI network is constructed first by combining the gene expression data of proteins with topological information extracted from the original PPI network. Simultaneously, a weighted domain-domain interaction (DDI) network is constructed based on the original PDI network. Next, through integrating the newly obtained weighted PPI network and weighted DDI network with the original PDI network, a weighted PDI network is further constructed. Then, based on topological features and biological information, including the subcellular localization and orthologous information of proteins, a novel PageRank-based iterative algorithm is designed and implemented on the newly constructed weighted PDI network to estimate the criticality of proteins. Finally, to assess the prediction performance of WPDINM, we compared it with 12 kinds of competitive measures. Experimental results show that WPDINM can achieve a predictive accuracy rate of 90.19, 81.96, 70.72, 62.04, 55.83, and 51.13% in the top 1%, top 5%, top 10%, top 15%, top 20%, and top 25% separately, which exceeds the prediction accuracy achieved by traditional state-of-the-art competing measures. Owing to the satisfactory identification effect, the WPDINM measure may contribute to the further development of key protein identification.

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A Novel Method for Identifying Essential Proteins Based on Non-negative Matrix Tri-Factorization

Frontiers in Genetics ◽

10.3389/fgene.2021.709660 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhihong Zhang ◽

Meiping Jiang ◽

Dongjie Wu ◽

Wang Zhang ◽

Wei Yan ◽

...

Keyword(s):

Protein Interaction ◽

Protein Interactions ◽

Negative Impact ◽

False Negative ◽

Interaction Network ◽

Biological Information ◽

Ppi Network ◽

Essential Proteins ◽

Protein Protein Interaction ◽

Ppi Networks

Identification of essential proteins is very important for understanding the basic requirements to sustain a living organism. In recent years, there has been an increasing interest in using computational methods to predict essential proteins based on protein–protein interaction (PPI) networks or fusing multiple biological information. However, it has been observed that existing PPI data have false-negative and false-positive data. The fusion of multiple biological information can reduce the influence of false data in PPI, but inevitably more noise data will be produced at the same time. In this article, we proposed a novel non-negative matrix tri-factorization (NMTF)-based model (NTMEP) to predict essential proteins. Firstly, a weighted PPI network is established only using the topology features of the network, so as to avoid more noise. To reduce the influence of false data (existing in PPI network) on performance of identify essential proteins, the NMTF technique, as a widely used recommendation algorithm, is performed to reconstruct a most optimized PPI network with more potential protein–protein interactions. Then, we use the PageRank algorithm to compute the final ranking score of each protein, in which subcellular localization and homologous information of proteins were used to calculate the initial scores. In addition, extensive experiments are performed on the publicly available datasets and the results indicate that our NTMEP model has better performance in predicting essential proteins against the start-of-the-art method. In this investigation, we demonstrated that the introduction of non-negative matrix tri-factorization technology can effectively improve the condition of the protein–protein interaction network, so as to reduce the negative impact of noise on the prediction. At the same time, this finding provides a more novel angle of view for other applications based on protein–protein interaction networks.

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

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqab010 ◽

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.

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A Non-negative Matrix Factorization Based Method for Identifying Essential Proteins

10.21203/rs.3.rs-537545/v1 ◽

2021 ◽

Author(s):

Zhihong Zhang ◽

Sai Hu ◽

Wei Yan ◽

Bihai Zhao ◽

Lei Wang

Keyword(s):

Protein Interaction ◽

Matrix Factorization ◽

Biological Data ◽

Protein Domain ◽

Biological Information ◽

Ppi Network ◽

Essential Proteins ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Non Negative Matrix Factorization

Abstract BackgroundIdentification of essential proteins is very important for understanding the basic requirements to sustain a living organism. In recent years, various different computational methods have been proposed to identify essential proteins based on protein-protein interaction (PPI) networks. However, there has been reliable evidence that a huge amount of false negatives and false positives exist in PPI data. Therefore, it is necessary to reduce the influence of false data on accuracy of essential proteins prediction by integrating multi-source biological information with PPI networks.ResultsIn this paper, we proposed a non-negative matrix factorization and multiple biological information based model (NDM) for identifying essential proteins. The first stage in this progress was to construct a weighted PPI network by combing the information of protein domain, protein complex and the topology characteristic of the original PPI network. Then, the non-negative matrix factorization technique was used to reconstruct an optimized PPI network with whole enough weight of edges. In the final stage, the ranking score of each protein was computed by the PageRank algorithm in which the initial scores were calculated with homologous and subcellular localization information. In order to verify the effectiveness of the NDM method, we compared the NDM with other state-of-the-art essential proteins prediction methods. The comparison of the results obtained from different methods indicated that our NDM model has better performance in predicting essential proteins.ConclusionEmploying the non-negative matrix factorization and integrating multi-source biological data can effectively improve quality of the PPI network, which resulted in the led to optimization of the performance essential proteins identification. This will also provide a new perspective for other prediction based on protein-protein interaction networks.

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Extracting Biological Significant Subnetworks from Protein-Protein Interactions Induced by Differentially Expressed Genes of HIV-1 Vpr Variants

International Journal of System Dynamics Applications ◽

10.4018/ijsda.2015100103 ◽

2015 ◽

Vol 4 (4) ◽

pp. 35-51 ◽

Cited By ~ 1

Author(s):

Bandana Barman ◽

Anirban Mukhopadhyay

Keyword(s):

Differentially Expressed Genes ◽

Protein Interaction ◽

Protein Interactions ◽

Protein Interaction Network ◽

Interaction Network ◽

Differentially Expressed ◽

Wild Type ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Hiv 1

Identification of protein interaction network is very important to find the cell signaling pathway for a particular disease. The authors have found the differentially expressed genes between two sample groups of HIV-1. Samples are wild type HIV-1 Vpr and HIV-1 mutant Vpr. They did statistical t-test and found false discovery rate (FDR) to identify the genes increased in expression (up-regulated) or decreased in expression (down-regulated). In the test, the authors have computed q-values of test to identify minimum FDR which occurs. As a result they found 172 differentially expressed genes between their sample wild type HIV-1 Vpr and HIV-1 mutant Vpr, R80A. They found 68 up-regulated genes and 104 down-regulated genes. From the 172 differentially expressed genes the authors found protein-protein interaction network with string-db and then clustered (subnetworks) the PPI networks with cytoscape3.0. Lastly, the authors studied significance of subnetworks with performing gene ontology and also studied the KEGG pathway of those subnetworks.

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Integration of anatomy ontology data with protein–protein interaction networks improves the candidate gene prediction accuracy for anatomical entities

BMC Bioinformatics ◽

10.1186/s12859-020-03773-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Pasan C. Fernando ◽

Paula M. Mabee ◽

Erliang Zeng

Keyword(s):

Candidate Gene ◽

Candidate Genes ◽

Gene Networks ◽

Prediction Accuracy ◽

Gene Prediction ◽

Anatomical Entity ◽

Anatomy Ontology ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Entity Relationships

Abstract Background Identification of genes responsible for anatomical entities is a major requirement in many fields including developmental biology, medicine, and agriculture. Current wet lab techniques used for this purpose, such as gene knockout, are high in resource and time consumption. Protein–protein interaction (PPI) networks are frequently used to predict disease genes for humans and gene candidates for molecular functions, but they are rarely used to predict genes for anatomical entities. Moreover, PPI networks suffer from network quality issues, which can be a limitation for their usage in predicting candidate genes. Therefore, we developed an integrative framework to improve the candidate gene prediction accuracy for anatomical entities by combining existing experimental knowledge about gene-anatomical entity relationships with PPI networks using anatomy ontology annotations. We hypothesized that this integration improves the quality of the PPI networks by reducing the number of false positive and false negative interactions and is better optimized to predict candidate genes for anatomical entities. We used existing Uberon anatomical entity annotations for zebrafish and mouse genes to construct gene networks by calculating semantic similarity between the genes. These anatomy-based gene networks were semantic networks, as they were constructed based on the anatomy ontology annotations that were obtained from the experimental data in the literature. We integrated these anatomy-based gene networks with mouse and zebrafish PPI networks retrieved from the STRING database and compared the performance of their network-based candidate gene predictions. Results According to evaluations of candidate gene prediction performance tested under four different semantic similarity calculation methods (Lin, Resnik, Schlicker, and Wang), the integrated networks, which were semantically improved PPI networks, showed better performances by having higher area under the curve values for receiver operating characteristic and precision-recall curves than PPI networks for both zebrafish and mouse. Conclusion Integration of existing experimental knowledge about gene-anatomical entity relationships with PPI networks via anatomy ontology improved the candidate gene prediction accuracy and optimized them for predicting candidate genes for anatomical entities.

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Nonessential-Nonhub Proteins in the Protein-Protein Interaction Network

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.934.159 ◽

2014 ◽

Vol 934 ◽

pp. 159-164

Author(s):

Yun Yuan Dong ◽

Xian Chun Zhang

Keyword(s):

Protein Interaction ◽

Interaction Network ◽

Clustering Coefficient ◽

Centrality Measures ◽

Ppi Network ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Comparison Results ◽

A Cell ◽

High Degree

Protein-protein interaction (PPI) networks provide a simplified overview of the web of interactions that take place inside a cell. According to the centrality-lethality rule, hub proteins (proteins with high degree) tend to be essential in the PPI network. Moreover, there are also many low degree proteins in the PPI network, but they have different lethality. Some of them are essential proteins (essential-nonhub proteins), and the others are not (nonessential-nonhub proteins). In order to explain why nonessential-nonhub proteins don’t have essentiality, we propose a new measure n-iep (the number of essential neighbors) and compare nonessential-nonhub proteins with essential-nonhub proteins from topological, evolutionary and functional view. The comparison results show that there are statistical differences between nonessential-nonhub proteins and essential-nonhub proteins in centrality measures, clustering coefficient, evolutionary rate and the number of essential neighbors. These are reasons why nonessential-nonhub proteins don’t have lethality.

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PREDICTION OF ESSENTIAL PROTEINS BASED ON EDGE CLUSTERING COEFFICIENT AND GENE ONTOLOGY INFORMATION

Journal of Biological System ◽

10.1142/s0218339014500119 ◽

2014 ◽

Vol 22 (03) ◽

pp. 339-351 ◽

Cited By ~ 3

Author(s):

JIAWEI LUO ◽

NAN ZHANG

Keyword(s):

Gene Ontology ◽

Network Topology ◽

Clustering Coefficient ◽

Ppi Network ◽

Essential Proteins ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Survival And Development ◽

Gene Ontology Information ◽

Better Than

Essential proteins are important for the survival and development of organisms. Lots of centrality algorithms based on network topology have been proposed to detect essential proteins and achieve good results. However, most of them only focus on the network topology, but ignore the false positive (FP) interactions in protein–protein interaction (PPI) network. In this paper, gene ontology (GO) information is proposed to measure the reliability of the edges in PPI network and we propose a novel algorithm for identifying essential proteins, named EGC algorithm. EGC algorithm integrates topology character of PPI network and GO information. To validate the performance of EGC algorithm, we use EGC and other nine methods (DC, BC, CC, SC, EC, LAC, NC, PEC and CoEWC) to identify the essential proteins in the two different yeast PPI networks: DIP and MIPS. The results show that EGC is better than the other nine methods, which means adding GO information can help in predicting essential proteins.

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Comparing protein-protein interaction networks of SARS-CoV-2 and (H1N1) influenza using topological features

10.1101/2021.11.02.463717 ◽

2021 ◽

Author(s):

Hakimeh Khojasteh ◽

Alireza Khanteymoori ◽

Mohammad Hossein Olyaee

Keyword(s):

Dimensionality Reduction ◽

Power Law ◽

Protein Interaction ◽

Interaction Network ◽

H1n1 Influenza ◽

Centrality Measures ◽

Essential Proteins ◽

Protein Protein Interaction ◽

Topological Features ◽

High Level

Background: SARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 183 million individuals and caused about 4 million deaths globally. A protein-protein interaction network (PPIN) and its analysis can provide insight into the behavior of cells and lead to advance the procedure of drug discovery. The identification of essential proteins is crucial to understand for cellular survival. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common proteins. Analyzing influential proteins and comparing these networks together can be an effective step helping biologists in drug design. Results: We used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. PCA-based dimensionality reduction was applied on normalized centrality values. Some measures demonstrated a high level of contribution in comparison to others in both PPINs, like Barycenter, Decay, Diffusion degree, Closeness (Freeman), Closeness (Latora), Lin, Radiality, and Residual. Using validation measures, the appropriate clustering method was chosen for centrality measures. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness. Conclusions: Through analysis and comparison, both networks exhibited remarkable experimental results. The network diameters were equal and in terms of heterogeneity, SARS-CoV-2 PPIN tends to be more heterogeneous. Both networks under study display a typical power-law degree distribution. Dimensionality reduction and unsupervised learning methods were so effective to reveal appropriate centrality measures.

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