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.
Existing studies demonstrate that the genes or gene products with similar expression patterns tend to have the similar biological function in a period of life, and also more likely to contact each other to form a dense functional module in PPI networks @cite_2 . Therefore, proteins' GED data are used in this work to evaluate the similarity of proteins in a PPI network @cite_15 @cite_17 . Ji . @cite_15 introduced a multiple-grain model to detect functional modules from large-scale PPI networks. Spirin . @cite_17 presented an enumeration method to find completely connected subgraphs, and then to search for protein functional module. GN algorithm @cite_13 is a classical community discovery algorithm. Depending on high cohesion for internal communities and low cohesion among communities, structures of cohesive communities are relatively detected by gradually removing the edges among communities. Louvain @cite_16 is a fast aggregation algorithm that is used to extract the community structure in large networks, using a heuristic method based on modularity optimization. SPICi @cite_6 is a clustering algorithm for discovering protein complexes and functional modules from PPI networks.
@cite_6 @cite_2 @cite_15 @cite_16 @cite_13 @cite_17
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Motivation: With the exponential growth of expression and protein–protein interaction (PPI) data, the frontier of research in systems biology shifts more and more to the integrated analysis of these large datasets. Of particular interest is the identification of functional modules in PPI networks, sharing common cellular function beyond the scope of classical pathways, by means of detecting differentially expressed regions in PPI networks. This requires on the one hand an adequate scoring of the nodes in the network to be identified and on the other hand the availability of an effective algorithm to find the maximally scoring network regions. Various heuristic approaches have been proposed in the literature. Results: Here we present the first exact solution for this problem, which is based on integer-linear programming and its connection to the well-known prize-collecting Steiner tree problem from Operations Research. Despite the NP-hardness of the underlying combinatorial problem, our method typically computes provably optimal subnetworks in large PPI networks in a few minutes. An essential ingredient of our approach is a scoring function defined on network nodes. We propose a new additive score with two desirable properties: (i) it is scalable by a statistically interpretable parameter and (ii) it allows a smooth integration of data from various sources. We apply our method to a well-established lymphoma microarray dataset in combination with associated survival data and the large interaction network of HPRD to identify functional modules by computing optimal-scoring subnetworks. In particular, we find a functional interaction module associated with proliferation over-expressed in the aggressive ABC subtype as well as modules derived from non-malignant by-stander cells. Availability: Our software is available freely for non-commercial purposes at http: www.planet-lisa.net. Contact: tobias.mueller@biozentrum.uni-wuerzburg.de Motivation: Clustering algorithms play an important role in the analysis of biological networks, and can be used to uncover functional modules and obtain hints about cellular organization. While most available clustering algorithms work well on biological networks of moderate size, such as the yeast protein physical interaction network, they either fail or are too slow in practice for larger networks, such as functional networks for higher eukaryotes. Since an increasing number of larger biological networks are being determined, the limitations of current clustering approaches curtail the types of biological network analyses that can be performed. Results: We present a fast local network clustering algorithm SPICi. SPICi runs in time O(V log V+E) and space O(E), where V and E are the number of vertices and edges in the network, respectively. We evaluate SPICi's performance on several existing protein interaction networks of varying size, and compare SPICi to nine previous approaches for clustering biological networks. We show that SPICi is typically several orders of magnitude faster than previous approaches and is the only one that can successfully cluster all test networks within very short time. We demonstrate that SPICi has state-of-the-art performance with respect to the quality of the clusters it uncovers, as judged by its ability to recapitulate protein complexes and functional modules. Finally, we demonstrate the power of our fast network clustering algorithm by applying SPICi across hundreds of large context-specific human networks, and identifying modules specific for single conditions. Availability: Source code is available under the GNU Public License at http: compbio.cs.princeton.edu spici Contact: ude.notecnirp.sc@anom Supplementary information: Supplementary data are available at Bioinformatics online. Motivation: Discovering and understanding patterns in networks of protein–protein interactions (PPIs) is a central problem in systems biology. Alignments between these networks aid functional understanding as they uncover important information, such as evolutionary conserved pathways, protein complexes and functional orthologs. A few methods have been proposed for global PPI network alignments, but because of NP-completeness of underlying sub-graph isomorphism problem, producing topologically and biologically accurate alignments remains a challenge. Results: We introduce a novel global network alignment tool, Lagrangian GRAphlet-based ALigner (L-GRAAL), which directly optimizes both the protein and the interaction functional conservations, using a novel alignment search heuristic based on integer programming and Lagrangian relaxation. We compare L-GRAAL with the state-of-the-art network aligners on the largest available PPI networks from BioGRID and observe that L-GRAAL uncovers the largest common sub-graphs between the networks, as measured by edge-correctness and symmetric sub-structures scores, which allow transferring more functional information across networks. We assess the biological quality of the protein mappings using the semantic similarity of their Gene Ontology annotations and observe that L-GRAAL best uncovers functionally conserved proteins. Furthermore, we introduce for the first time a measure of the semantic similarity of the mapped interactions and show that L-GRAAL also uncovers best functionally conserved interactions. In addition, we illustrate on the PPI networks of baker's yeast and human the ability of L-GRAAL to predict new PPIs. Finally, L-GRAAL's results are the first to show that topological information is more important than sequence information for uncovering functionally conserved interactions. Availability and implementation: L-GRAAL is coded in C++. Software is available at: http: bio-nets.doc.ic.ac.uk L-GRAAL . Contact: ku.ca.lairepmi@ningod-dolam.n Supplementary information: Supplementary data are available at Bioinformatics online. Motivation: High-throughput methods for detecting molecular interactions have produced large sets of biological network data with much more yet to come. Analogous to sequence alignment, efficient and reliable network alignment methods are expected to improve our understanding of biological systems. Unlike sequence alignment, network alignment is computationally intractable. Hence, devising efficient network alignment heuristics is currently a foremost challenge in computational biology. Results: We introduce a novel network alignment algorithm, called Matching-based Integrative GRAph ALigner (MI-GRAAL), which can integrate any number and type of similarity measures between network nodes (e.g. proteins), including, but not limited to, any topological network similarity measure, sequence similarity, functional similarity and structural similarity. Hence, we resolve the ties in similarity measures and find a combination of similarity measures yielding the largest contiguous (i.e. connected) and biologically sound alignments. MI-GRAAL exposes the largest functional, connected regions of protein–protein interaction (PPI) network similarity to date: surprisingly, it reveals that 77.7 of proteins in the baker's yeast high-confidence PPI network participate in such a subnetwork that is fully contained in the human high-confidence PPI network. This is the first demonstration that species as diverse as yeast and human contain so large, continuous regions of global network similarity. We apply MI-GRAAL's alignments to predict functions of un-annotated proteins in yeast, human and bacteria validating our predictions in the literature. Furthermore, using network alignment scores for PPI networks of different herpes viruses, we reconstruct their phylogenetic relationship. This is the first time that phylogeny is exactly reconstructed from purely topological alignments of PPI networks. Availability: Supplementary files and MI-GRAAL executables: http: bio-nets.doc.ic.ac.uk MI-GRAAL . Contact: natasha@imperial.ac.uk Supplementary information:Supplementary data are available at Bioinformatics online.