scholarly journals From the static interactome to dynamic protein complexes: Three challenges

2015 ◽  
Vol 13 (02) ◽  
pp. 1571001 ◽  
Author(s):  
Chern Han Yong ◽  
Limsoon Wong
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Clustering Algorithms ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Static Interaction ◽  
Ppi Networks ◽  
Interaction Screening ◽  
Discovery Algorithms ◽  
Insight Into

Protein interactions and complexes behave in a dynamic fashion, but this dynamism is not captured by interaction screening technologies, and not preserved in protein–protein interaction (PPI) networks. The analysis of static interaction data to derive dynamic protein complexes leads to several challenges, of which we identify three. First, many proteins participate in multiple complexes, leading to overlapping complexes embedded within highly-connected regions of the PPI network. This makes it difficult to accurately delimit the boundaries of such complexes. Second, many condition- and location-specific PPIs are not detected, leading to sparsely-connected complexes that cannot be picked out by clustering algorithms. Third, the majority of complexes are small complexes (made up of two or three proteins), which are extra sensitive to the effects of extraneous edges and missing co-complex edges. We show that many existing complex-discovery algorithms have trouble predicting such complexes, and show that our insight into the disparity between the static interactome and dynamic protein complexes can be used to improve the performance of complex discovery.

scholarly journals Entropy-Based Graph Clustering of PPI Networks for Predicting Overlapping Functional Modules of Proteins

Entropy ◽  
2021 ◽  
Vol 23 (10) ◽  
pp. 1271
Author(s):  
Hoyeon Jeong ◽  
Yoonbee Kim ◽  
Yi-Sue Jung ◽  
Dae Ryong Kang ◽  
Young-Rae Cho
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Clustering Algorithms ◽  
Graph Clustering ◽  
Functional Modules ◽  
Protein Protein Interactions ◽  
Overlapping Clusters ◽  
Novel Proteins ◽  
Ppi Networks ◽  
Function Modules

Functional modules can be predicted using genome-wide protein–protein interactions (PPIs) from a systematic perspective. Various graph clustering algorithms have been applied to PPI networks for this task. In particular, the detection of overlapping clusters is necessary because a protein is involved in multiple functions under different conditions. graph entropy (GE) is a novel metric to assess the quality of clusters in a large, complex network. In this study, the unweighted and weighted GE algorithm is evaluated to prove the validity of predicting function modules. To measure clustering accuracy, the clustering results are compared to protein complexes and Gene Ontology (GO) annotations as references. We demonstrate that the GE algorithm is more accurate in overlapping clusters than the other competitive methods. Moreover, we confirm the biological feasibility of the proteins that occur most frequently in the set of identified clusters. Finally, novel proteins for the additional annotation of GO terms are revealed.

scholarly journals Identifying Hierarchical and Overlapping Protein Complexes Based on Essential Protein-Protein Interactions and “Seed-Expanding” Method

2014 ◽  
Vol 2014 ◽  
pp. 1-12
Author(s):  
Jun Ren ◽  
Wei Zhou ◽  
Jianxin Wang
Keyword(s):  
Protein Interactions ◽  
Time Complexity ◽  
Protein Complexes ◽  
Hierarchical Organization ◽  
Experimental Results ◽  
Functional Enrichment ◽  
Detection Methods ◽  
Ppi Network ◽  
Protein Protein Interactions ◽  
Ppi Networks

Many evidences have demonstrated that protein complexes are overlapping and hierarchically organized in PPI networks. Meanwhile, the large size of PPI network wants complex detection methods have low time complexity. Up to now, few methods can identify overlapping and hierarchical protein complexes in a PPI network quickly. In this paper, a novel method, called MCSE, is proposed based onλ-module and “seed-expanding.” First, it chooses seeds as essential PPIs or edges with high edge clustering values. Then, it identifies protein complexes by expanding each seed to aλ-module. MCSE is suitable for large PPI networks because of its low time complexity. MCSE can identify overlapping protein complexes naturally because a protein can be visited by different seeds. MCSE uses the parameterλ_th to control the range of seed expanding and can detect a hierarchical organization of protein complexes by tuning the value ofλ_th. Experimental results ofS. cerevisiaeshow that this hierarchical organization is similar to that of known complexes in MIPS database. The experimental results also show that MCSE outperforms other previous competing algorithms, such as CPM, CMC, Core-Attachment, Dpclus, HC-PIN, MCL, and NFC, in terms of the functional enrichment and matching with known protein complexes.

scholarly journals Resilience and evolvability of protein-protein interaction networks

2020 ◽  
Author(s):  
Brennan Klein ◽  
Ludvig Holmér ◽  
Keith M. Smith ◽  
Mackenzie M. Johnson ◽  
Anshuman Swain ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Preferential Attachment ◽  
Network Resilience ◽  
Biological Noise ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Ppi Networks

AbstractProtein-protein interaction (PPI) networks represent complex intra-cellular protein interactions, and the presence or absence of such interactions can lead to biological changes in an organism. Recent network-based approaches have shown that a phenotype’s PPI network’s resilience to environmental perturbations is related to its placement in the tree of life; though we still do not know how or why certain intra-cellular factors can bring about this resilience. One such factor is gene expression, which controls the simultaneous presence of proteins for allowed extant interactions and the possibility of novel associations. Here, we explore the influence of gene expression and network properties on a PPI network’s resilience, focusing especially on ribosomal proteins—vital molecular-complexes involved in protein synthesis, which have been extensively and reliably mapped in many species. Using publicly-available data of ribosomal PPIs for E. coli, S.cerevisae, and H. sapiens, we compute changes in network resilience as new nodes (proteins) are added to the networks under three node addition mechanisms—random, degree-based, and gene-expression-based attachments. By calculating the resilience of the resulting networks, we estimate the effectiveness of these node addition mechanisms. We demonstrate that adding nodes with gene-expression-based preferential attachment (as opposed to random or degree-based) preserves and can increase the original resilience of PPI network. This holds in all three species regardless of their distributions of gene expressions or their network community structure. These findings introduce a general notion of prospective resilience, which highlights the key role of network structures in understanding the evolvability of phenotypic traits.1Author SummaryProteins in organismal cells are present at different levels of concentration and interact with other proteins to provide specific functional roles. Accumulating lists of all of these interactions, complex networks of protein interactions become apparent. This allows us to begin asking whether there are network-level mechanisms at play guiding the evolution of biological systems. Here, using this network perspective, we address two important themes in evolutionary biology (i) How are biological systems able to successfully incorporate novelty? (ii) What is the evolutionary role of biological noise in evolutionary novelty? We consider novelty to be the introduction of a new protein, represented as a new “node”, into a network. We simulate incorporation of novel proteins into Protein-Protein Interaction (PPI) networks in different ways and analyse how the resilience of the PPI network alters. We find that novel interactions guided by gene expression (indicative of concentration levels of proteins) creates a more resilient network than either uniformly random interactions or interactions guided solely by the network structure (preferential attachment). Moreover, simulated biological noise in the gene expression increases network resilience. We suggest that biological noise induces novel structure in the PPI network which has the effect of making it more resilient.

scholarly journals SETS: A Seed-Dense-Expanding Model-Based Topological Structure for the Prediction of Overlapping Protein Complexes

2021 ◽  
Vol 29 (2) ◽  
Author(s):  
Soheir Noori ◽  
Nabeel Al-A’araji ◽  
Eman Al-Shamery
Keyword(s):  
Protein Interaction ◽  
Execution Time ◽  
Topological Structure ◽  
Protein Complexes ◽  
Biological Cell ◽  
Ppi Network ◽  
High Similarity ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
F Measure

Defining protein complexes by analysing the protein–protein interaction (PPI) networks is a crucial task in understanding the principles of a biological cell. In the last few decades, researchers have proposed numerous methods to explore the topological structure of a PPI network to detect dense protein complexes. In this paper, the overlapping protein complexes with different densities are predicted within an acceptable execution time using seed expanding model and topological structure of the PPI network (SETS). SETS depend on the relation between the seed and its neighbours. The algorithm was compared with six algorithms on six datasets: five for yeast and one for human. The results showed that SETS outperformed other algorithms in terms of F-measure, coverage rate and the number of complexes that have high similarity with real complexes.

scholarly journals Protein-Protein Interactions Prediction Based on Iterative Clique Extension with Gene Ontology Filtering

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Lei Yang ◽  
Xianglong Tang
Keyword(s):  
Gene Ontology ◽  
Protein Interactions ◽  
Protein Complexes ◽  
False Negative ◽  
Biological Database ◽  
Interacting Proteins ◽  
Ppi Network ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Biological Meaning

Cliques (maximal complete subnets) in protein-protein interaction (PPI) network are an important resource used to analyze protein complexes and functional modules. Clique-based methods of predicting PPI complement the data defection from biological experiments. However, clique-based predicting methods only depend on the topology of network. The false-positive and false-negative interactions in a network usually interfere with prediction. Therefore, we propose a method combining clique-based method of prediction and gene ontology (GO) annotations to overcome the shortcoming and improve the accuracy of predictions. According to different GO correcting rules, we generate two predicted interaction sets which guarantee the quality and quantity of predicted protein interactions. The proposed method is applied to the PPI network from the Database of Interacting Proteins (DIP) and most of the predicted interactions are verified by another biological database, BioGRID. The predicted protein interactions are appended to the original protein network, which leads to clique extension and shows the significance of biological meaning.

CLUSTERING ALGORITHMS FOR DETECTING FUNCTIONAL MODULES IN PROTEIN INTERACTION NETWORKS

2009 ◽  
Vol 07 (01) ◽  
pp. 217-242 ◽  
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.

scholarly journals A Least Square Method Based Model for Identifying Protein Complexes in Protein-Protein Interaction Network

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Qiguo Dai ◽  
Maozu Guo ◽  
Yingjie Guo ◽  
Xiaoyan Liu ◽  
Yang Liu ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Least Squares Method ◽  
Protein Complexes ◽  
Interaction Network ◽  
Least Square Method ◽  
Least Square ◽  
Great Effort ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Ppi Networks

Protein complex formed by a group of physical interacting proteins plays a crucial role in cell activities. Great effort has been made to computationally identify protein complexes from protein-protein interaction (PPI) network. However, the accuracy of the prediction is still far from being satisfactory, because the topological structures of protein complexes in the PPI network are too complicated. This paper proposes a novel optimization framework to detect complexes from PPI network, named PLSMC. The method is on the basis of the fact that if two proteins are in a common complex, they are likely to be interacting. PLSMC employs this relation to determine complexes by a penalized least squares method. PLSMC is applied to several public yeast PPI networks, and compared with several state-of-the-art methods. The results indicate that PLSMC outperforms other methods. In particular, complexes predicted by PLSMC can match known complexes with a higher accuracy than other methods. Furthermore, the predicted complexes have high functional homogeneity.

idenPC-CAP: Identify protein complexes from weighted RNA-protein heterogeneous interaction networks using co-assemble partner relation

2020 ◽  
Author(s):  
Zhourun Wu ◽  
Qing Liao ◽  
Shixi Fan ◽  
Bin Liu
Keyword(s):  
Computational Methods ◽  
Protein Interactions ◽  
False Positive ◽  
Protein Complexes ◽  
Interaction Network ◽  
Computational Method ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Ppi Networks ◽  
Heterogeneous Interaction

Abstract Protein complexes play important roles in most cellular processes. The available genome-wide protein–protein interaction (PPI) data make it possible for computational methods identifying protein complexes from PPI networks. However, PPI datasets usually contain a large ratio of false positive noise. Moreover, different types of biomolecules in a living cell cooperate to form a union interaction network. Because previous computational methods focus only on PPIs ignoring other types of biomolecule interactions, their predicted protein complexes often contain many false positive proteins. In this study, we develop a novel computational method idenPC-CAP to identify protein complexes from the RNA-protein heterogeneous interaction network consisting of RNA–RNA interactions, RNA-protein interactions and PPIs. By considering interactions among proteins and RNAs, the new method reduces the ratio of false positive proteins in predicted protein complexes. The experimental results demonstrate that idenPC-CAP outperforms the other state-of-the-art methods in this field.

scholarly journals Uncovering Biological Network Function via Graphlet Degree Signatures

2008 ◽  
Vol 6 ◽  
pp. CIN.S680 ◽  
Author(s):  
Tijana Milenković ◽  
Nataša Pržulj
Keyword(s):  
Protein Function ◽  
Biological Function ◽  
Protein Complexes ◽  
Local Network ◽  
Ppi Network ◽  
Graph Theoretic ◽  
Protein Protein Interaction ◽  
Network Function ◽  
Ppi Networks ◽  
Disease Protein

Motivation Proteins are essential macromolecules of life and thus understanding their function is of great importance. The number of functionally unclassified proteins is large even for simple and well studied organisms such as baker's yeast. Methods for determining protein function have shifted their focus from targeting specific proteins based solely on sequence homology to analyses of the entire proteome based on protein-protein interaction (PPI) networks. Since proteins interact to perform a certain function, analyzing structural properties of PPI networks may provide useful clues about the biological function of individual proteins, protein complexes they participate in, and even larger subcellular machines. Results We design a sensitive graph theoretic method for comparing local structures of node neighborhoods that demonstrates that in PPI networks, biological function of a node and its local network structure are closely related. The method summarizes a protein's local topology in a PPI network into the vector of graphlet degrees called the signature of the protein and computes the signature similarities between all protein pairs. We group topologically similar proteins under this measure in a PPI network and show that these protein groups belong to the same protein complexes, perform the same biological functions, are localized in the same subcellular compartments, and have the same tissue expressions. Moreover, we apply our technique on a proteome-scale network data and infer biological function of yet unclassified proteins demonstrating that our method can provide valuable guidelines for future experimental research such as disease protein prediction. Availability Data is available upon request.

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

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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