Protein interactions constitute the fundamental building block of almost every life activity. Identifying protein communities from Protein-Protein Interaction (PPI) networks is essential to understand the principles of cellular organization and explore the causes of various diseases. It is critical to integrate multiple data resources to identify reliable protein communities that have biological significance and improve the performance of community detection methods for large-scale PPI networks. In this paper, we propose a Multi-source Learning based Protein Community Detection (MLPCD) algorithm by integrating Gene Expression Data (GED) and a parallel solution of MLPCD using cloud computing technology. To effectively discover the biological functions of proteins that participating in different cellular processes, GED under different conditions is integrated with the original PPI network to reconstruct a Weighted-PPI (WPPI) network. To flexibly identify protein communities of different scales, we define community modularity and functional cohesion measurements and detect protein communities from WPPI using an agglomerative method. In addition, we respectively compare the detected communities with known protein complexes and evaluate the functional enrichment of protein function modules using Gene Ontology annotations. Moreover, we implement a parallel version of the MLPCD algorithm on the Apache Spark platform to enhance the performance of the algorithm for large-scale realistic PPI networks. Extensive experimental results indicate the superiority and notable advantages of the MLPCD algorithm over the relevant algorithms in terms of accuracy and performance.
@cite_18: Protein-protein interaction (PPI) plays a key role in understanding cellular mechanisms in different organisms. Many supervised classifiers like Random Forest (RF) and Support Vector Machine (SVM) have been used for intra or inter-species interaction prediction. For improving the prediction performance, in this paper we propose a novel set of features to represent a protein pair using their annotated Gene Ontology (GO) terms, including their ancestors. In our approach, a protein pair is treated as a document (bag of words), where the terms annotating the two proteins represent the words. Feature value of each word is calculated using information content of the corresponding term multiplied by a coefficient, which represents the weight of that term inside a document (i.e., a protein pair). We have tested the performance of the classifier using the proposed feature on different well known data sets of different species like S. cerevisiae, H. Sapiens, E. Coli, and D. melanogaster . We compare it with the other GO based feature representation technique, and demonstrate its competitive performance.
@cite_14: A protein-protein interaction (PPI) network is a biomolecule relationship network that plays an important role in biological activities. Studies of functional modules in a PPI network contribute greatly to the understanding of biological mechanism. With the development of life science and computing science, a great amount of PPI data has been acquired by various experimental and computational approaches, which presents a significant challenge of detecting functional modules in a PPI network. To address this challenge, many functional module detecting methods have been developed. In this survey, we first analyze the existing problems in detecting functional modules and discuss the countermeasures in the data preprocess and postprocess. Second, we introduce some special metrics for distance or graph developed in clustering process of proteins. Third, we give a classification system of functional module detecting methods and describe some existing detection methods in each category. Fourth, we list databases in common use and conduct performance comparisons of several typical algorithms by popular measurements. Finally, we present the prospects and references for researchers engaged in analyzing PPI networks.
@cite_22: Essential proteins are indispensable for cellular life. It is of great significance to identify essential proteins that can help us understand the minimal requirements for cellular life and is also very important for drug design. However, identification of essential proteins based on experimental approaches are typically time-consuming and expensive. With the development of high-throughput technology in the post-genomic era, more and more protein-protein interaction data can be obtained, which make it possible to study essential proteins from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. Most of these topology based essential protein discovery methods were to use network centralities. In this paper, we investigate the essential proteins' topological characters from a completely new perspective. To our knowledge it is the first time that topology potential is used to identify essential proteins from a protein-protein interaction (PPI) network. The basic idea is that each protein in the network can be viewed as a material particle which creates a potential field around itself and the interaction of all proteins forms a topological field over the network. By defining and computing the value of each protein's topology potential, we can obtain a more precise ranking which reflects the importance of proteins from the PPI network. The experimental results show that topology potential-based methods TP and TP-NC outperform traditional topology measures: degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), subgraph centrality (SC), eigenvector centrality (EC), information centrality (IC), and network centrality (NC) for predicting essential proteins. In addition, these centrality measures are improved on their performance for identifying essential proteins in biological network when controlled by topology potential.
@cite_9: As advances in the technologies of predicting protein interactions, huge data sets portrayed as networks have been available. Identification of functional modules from such networks is crucial for understanding principles of cellular organization and functions. However, protein interaction data produced by high-throughput experiments are generally associated with high false positives, which makes it difficult to identify functional modules accurately. In this paper, we propose a fast hierarchical clustering algorithm HC-PIN based on the local metric of edge clustering value which can be used both in the unweighted network and in the weighted network. The proposed algorithm HC-PIN is applied to the yeast protein interaction network, and the identified modules are validated by all the three types of Gene Ontology (GO) Terms: Biological Process, Molecular Function, and Cellular Component. The experimental results show that HC-PIN is not only robust to false positives, but also can discover the functional modules with low density. The identified modules are statistically significant in terms of three types of GO annotations. Moreover, HC-PIN can uncover the hierarchical organization of functional modules with the variation of its parameter's value, which is approximatively corresponding to the hierarchical structure of GO annotations. Compared to other previous competing algorithms, our algorithm HC-PIN is faster and more accurate.
@cite_21: In recent years, a remarkable amount of protein-protein interaction (PPI) data are being available owing to the advance made in experimental high-throughput technologies. However, the experimentally detected PPI data usually contain a large amount of spurious links, which could contaminate the analysis of the biological significance of protein links and lead to incorrect biological discoveries, thereby posing new challenges to both computational and biological scientists. In this paper, we develop a new embedding algorithm called local similarity preserving embedding (LSPE) to rank the interaction possibility of protein links. By going beyond limitations of current geometric embedding methods for network denoising and emphasizing the local information of PPI networks, LSPE can avoid the unstableness of previous methods. We demonstrate experimental results on benchmark PPI networks and show that LSPE was the overall leader, outperforming the state-of-the-art methods in topological false links elimination problems.
@cite_10: Prediction of essential proteins which are crucial to an organism's survival is important for disease analysis and drug design, as well as the understanding of cellular life. The majority of prediction methods infer the possibility of proteins to be essential by using the network topology. However, these methods are limited to the completeness of available protein-protein interaction (PPI) data and depend on the network accuracy. To overcome these limitations, some computational methods have been proposed. However, seldom of them solve this problem by taking consideration of protein domains. In this work, we first analyze the correlation between the essentiality of proteins and their domain features based on data of 13 species. We find that the proteins containing more protein domain types which rarely occur in other proteins tend to be essential. Accordingly, we propose a new prediction method, named UDoNC, by combining the domain features of proteins with their topological properties in PPI network. In UDoNC, the essentiality of proteins is decided by the number and the frequency of their protein domain types, as well as the essentiality of their adjacent edges measured by edge clustering coefficient. The experimental results on S. cerevisiae data show that UDoNC outperforms other existing methods in terms of area under the curve (AUC). Additionally, UDoNC can also perform well in predicting essential proteins on data of E. coli.
The analysis of protein functions in PPI networks is a hot topic in Bioinformatics research. The main research streaming for PPI networks focuses on the detection of protein functional modules and analysis of the dynamic PPI networks' characteristic @cite_9 . Peng . @cite_10 proposed a Udonc algorithm for identifying essential proteins based on protein domains and PPI networks. Zhu . @cite_21 introduced a local similarity preserving embedding algorithm to identify spurious interactions in PPI networks. Sanghamitra . @cite_18 proposed a new feature vector based on gene ontology terms for PPI prediction, in which a protein pair is considered as a document and the terms annotating the two proteins represent the words. Ji . @cite_14 compared some functional module detection methods for PPI, and discussed the accuracy and performance of several typical algorithms. Li . @cite_22 discussed a topology potential-based method for identifying essential proteins from PPI networks. The previous protein modules detection approaches of PPI networks achieved a certain degree of success. However, most of the existing achievements detect protein communities only according to the topological structure of PPI networks, where the identified protein sub-cluster may not effectively reflect its biological significance.