Alignment Of Protein-protein Interaction Networks Research Articles

A protein-protein interaction network aligner study in the multi-objective domain

Background and ObjectiveThe protein-protein interaction (PPI) network alignment has proven to be an efficient technique in the diagnosis and prevention of certain diseases. However, the difficulty in maximizing, at the same time, the two qualities that measure the goodness of alignments (topological and biological quality) has led aligners to produce very different alignments. Thus making a comparative study among alignments of such different qualities a big challenge. Multi-objective optimization is a computer method, which is very powerful in this kind of contexts because both conflicting qualities are considered together. Analysing the alignments of each PPI network aligner with multi-objective methodologies allows you to visualize a bigger picture of the alignments and their qualities, obtaining very interesting conclusions. This paper proposes a comprehensive PPI network aligner study in the multi-objective domain. MethodsAlignments from each aligner and all aligners together were studied and compared to each other via Pareto dominance methodologies. The best alignments produced by each aligner and all aligners together for five different alignment scenarios were displayed in Pareto front graphs. Later, the aligners were ranked according to the topological, biological, and combined quality of their alignments. Finally, the aligners were also ranked based on their average runtimes. ResultsRegarding aligners constructing the best overall alignments, we found that SAlign, BEAMS, SANA, and HubAlign are the best options. Additionally, the alignments of best topological quality are produced by: SANA, SAlign, and HubAlign aligners. On the contrary, the aligners returning the alignments of best biological quality are: BEAMS, TAME, and WAVE. However, if there are time constraints, it is recommended to select SAlign to obtain high topological quality alignments and PISwap or SAlign aligners for high biological quality alignments. ConclusionsThe use of the SANA aligner is recommended for obtaining the best alignments of topological quality, BEAMS for alignments of the best biological quality, and SAlign for alignments of the best combined topological and biological quality. Simultaneously, SANA and BEAMS have above-average runtimes. Therefore, it is suggested, if necessary due to time restrictions, to choose other, faster aligners like SAlign or PISwap whose alignments are also of high quality.

GSLAlign: community detection and local PPI network alignment

High throughput protein–protein interaction (PPI) profiling and computational techniques have resulted in generating a large amount of PPI network data. The study of PPI networks helps in understanding the biological processes of the proteins. The comparative study of the PPI networks helps in identifying the conserved interactions across the species. This article presents a novel local PPI network aligner ‘GSLAlign’ that consists of two stages. It first detects the communities from the PPI networks by applying the GraphSAGE algorithm using gene expression data. In the second stage, the detected communities are aligned using a community aligner that is based on protein sequence similarity. The community detection algorithm produces more separable and biologically accurate communities as compared to previous community detection algorithms. Moreover, the proposed community alignment algorithm achieves 3–8% better results in terms of semantic similarity as compared to previous local aligners. The average connectivity and coverage of the proposed algorithm are also better than the existing aligners. Communicated by Ramaswamy H. Sarma

SAMNA: accurate alignment of multiple biological networks based on simulated annealing.

Proteins are important parts of the biological structures and encode a lot of biological information. Protein-protein interaction network alignment is a model for analyzing proteins that helps discover conserved functions between organisms and predict unknown functions. In particular, multi-network alignment aims at finding the mapping relationship among multiple network nodes, so as to transfer the knowledge across species. However, with the increasing complexity of PPI networks, how to perform network alignment more accurately and efficiently is a new challenge. This paper proposes a new global network alignment algorithm called Simulated Annealing Multiple Network Alignment (SAMNA), using both network topology and sequence homology information. To generate the alignment, SAMNA first generates cross-network candidate clusters by a clustering algorithm on a k-partite similarity graph constructed with sequence similarity information, and then selects candidate cluster nodes as alignment results and optimizes them using an improved simulated annealing algorithm. Finally, the SAMNA algorithm was experimented on synthetic and real-world network datasets, and the results showed that SAMNA outperformed the state-of-the-art algorithm in biological performance.

Transcriptomic Analysis of Mycobacterial Infected Macrophages Reveals a High MOI Specific Type I IFN Signaling.

Macrophage (MΦ) infection models are important tools for studying host-mycobacterial interactions. Although the multiplicity of infection (MOI) is an important experimental variable, the selection of MOI in mycobacterial infection experiments is largely empirical, without reference to solid experimental data. To provide relevant data, we used RNA-seq to analyze the gene expression profiles of MΦs 4 or 24 h after infection with Mycobacterium marinum (M. m) at MOIs ranging from 0.1 to 50. Analysis of differentially expressed genes (DEGs) showed that different MOIs are linked to distinct transcriptomic changes and only 10% of DEGs were shared by MΦ infected at all MOIs. KEGG pathway enrichment analysis revealed that type I interferon (IFN)-related pathways were inoculant dose-dependent and enriched only at high MOIs, whereas TNF pathways were inoculant dose-independent and enriched at all MOIs. Protein-protein interaction (PPI) network alignment showed that different MOIs had distinct key node genes. By fluorescence-activated cell sorting and follow-up RT-PCR analysis, we could separate infected MΦs from uninfected MΦs and found phagocytosis of mycobacteria to be the determinant factor for type I IFN production. The distinct transcriptional regulation of RAW264.7 MΦ genes at different MOIs was also seen with Mycobacterium tuberculosis (M.tb) infections and primary MΦ infection models. In summary, transcriptional profiling of mycobacterial infected MΦs revealed that different MOIs activate distinct immune pathways and the type I IFN pathway is activated only at high MOIs. This study should provide guidance for selecting the MOI most appropriate for different research questions.

Boosting-based ensemble of global network aligners for PPI network alignment

The number of investigations attempting to align protein–protein interaction (PPI) networks has increased with the growth of studies focused on collecting PPI data. These works aim to identify conserved areas between species that are difficult to differentiate due to speciation. However, there is no standard approach to align PPI networks, and global aligners encounter difficulties in constructing alignments with high biological and structural quality. To address this issue, we propose an innovative ensemble technique that combines the strengths of aligners in the PPI network alignment field while avoiding their weaknesses. This approach reduces the spread of dispersion in so different individual global aligners and contributes to achieving a global standard that produces alignments of higher quality. This is possible thanks to the two branches composing our ensemble that aim to improve alignments in terms of biological or structural quality. In addition to a new heuristic replacing the second-level aligner in the biological quality-focused branch. Our approach achieves alignments of higher quality, as demonstrated through experiments with 10 different scenarios involving real data from 5 species. Our solutions outperform other individual aligners and ensemble techniques, like bagging, in terms of biological and structural quality. Moreover, the time required to perform the ensemble is minimal compared to that of individual aligners.

An Extensive Assessment of Network Embedding in PPI Network Alignment.

Network alignment is a fundamental task in network analysis. In the biological field, where the protein–protein interaction (PPI) is represented as a graph, network alignment allowed the discovery of underlying biological knowledge such as conserved evolutionary pathways and functionally conserved proteins throughout different species. A recent trend in network science concerns network embedding, i.e., the modelling of nodes in a network as a low-dimensional feature vector. In this survey, we present an overview of current PPI network embedding alignment methods, a comparison among them, and a comparison to classical PPI network alignment algorithms. The results of this comparison highlight that: (i) only five network embeddings for network alignment algorithms have been applied in the biological context, whereas the literature presents several classical network alignment algorithms; (ii) there is a need for developing an evaluation framework that may enable a unified comparison between different algorithms; (iii) the majority of the proposed algorithms perform network embedding through matrix factorization-based techniques; (iv) three out of five algorithms leverage external biological resources, while the remaining two are designed for domain agnostic network alignment and tested on PPI networks; (v) two algorithms out of three are stated to perform multi-network alignment, while the remaining perform pairwise network alignment.

Decomposition-based multi-objective optimization approach for PPI network alignment

The alignment of protein–protein interaction (PPI) networks is in the spotlight of the research in bioinformatics. The main goal is to find structural or functional complexes that are evolutionarily conserved between species. Recent works in the area struggle to produce alignments of both good topological and functional quality, since those two objectives conflict more than expected. To this end, we introduce a decomposition-based multi-objective algorithm with two new problem-aware mutation operators, being each of them focused on the improvement of one of both objectives. The experiments have been performed over 10 scenarios of PPI network alignment with real data from five different species. The results have been evaluated with five quality metrics. The performed experiments have confirmed that the solutions resulting from our proposal obtain statistically significant improvements and are of higher quality than the solutions from related works.

On the current failure-but bright future-of topology-driven biological network alignment.

Since the function of a protein is defined by its interaction partners, and since we expect similar interaction patterns across species, the alignment of protein-protein interaction (PPI) networks between species, based on network topology alone, should uncover functionally related proteins across species. Surprisingly, despite the publication of more than fifty algorithms aimed at performing PPI network alignment, few have demonstrated a statistically significant link between network topology and functional similarity, and none have demonstrated that orthologs can be recovered using network topology alone. We find that the major contributing factors to this surprising failure are: (i) edge densities in most currently available experimental PPI networks are demonstrably too low to expect topological network alignment to succeed; (ii) in the few cases where the edge densities are high enough, some measures of topological similarity easily uncover functionally similar proteins while others do not; and (iii) most network alignment algorithms to date perform poorly at optimizing even their own topological objective functions, hampering their ability to use topology effectively. We demonstrate that SANA-the Simulated Annealing Network Aligner-significantly outperforms existing aligners at optimizing their own objective functions, even achieving near-optimal solutions when the optimal solution is known. We offer the first demonstration of global network alignments based on topology alone that align functionally similar proteins with p-values in some cases below 10-300. We predict that topological network alignment has a bright future as edge densities increase toward the value where good alignments become possible. We demonstrate that when enough common topology is present at high enough edge densities-for example in the recent, partly synthetic networks of the Integrated Interaction Database-topological network alignment easily recovers most orthologs, paving the way toward high-throughput functional prediction based on topology-driven network alignment.

The protein-protein interaction network alignment using recurrent neural network.

The main challenge of biological network alignment is that the problem of finding the alignments in two graphs is NP-hard. The discovery of protein-protein interaction (PPI) networks is of great importance in bioinformatics due to their utilization in identifying the cellular pathways, finding new medicines, and disease recognition. In this regard, we describe the network alignment method in the form of a classification problem for the very first time and introduce a deep network that finds the alignment of nodes present in the two networks. We call this method RENA, which means Network Alignment using REcurrent neural network. The proposed solution consists of three steps; in the first phase, we obtain the sequence and topological similarities from the networks' structure. For the second phase, the dataset needed for the transformation of the problem into a classification problem is created from obtained features. In the third phase, we predict the nodes' alignment between two networks using deep learning. We used Biogrid dataset for RENA evaluation. The RENA method is compared with three classification approaches of support vector machine, K-nearest neighbors, and linear discriminant analysis. The experimental results demonstrate the efficiency of the RENA method and 100% accuracy in PPI network alignment prediction.

Protein2Vec: Aligning Multiple PPI Networks with Representation Learning.

Research of Protein-Protein Interaction (PPI) Network Alignment is playing an important role in understanding the crucial underlying biological knowledge such as functionally homologous proteins and conserved evolutionary pathways across different species. Existing methods of PPI network alignment often try to improve the coverage ratio of the alignment result by aligning all proteins from different species. However, there is a fundamental biological premise that needs to be considered carefully: not every protein in a species can, nor should, find its homologous proteins in other species. In this work, we propose a novel alignment method to map only those proteins with the most similarity throughout the PPI networks of multiple species. For the similarity features of the protein in the networks, we integrate both topological features with biological characteristics to provide enhanced supports for the alignment procedures. For topological features, we apply a representation learning method on the networks and generate a low dimensional vector embedding with its surrounding structural features for each protein. The topological similarity of proteins from different PPI networks can thus be transferred as the similarity of their corresponding vector representations, which provides a new way to comprehensively quantify the topological similarities between proteins. We also propose a new measure for the topological evaluation of the alignment results which better uncover the structural quality of the alignment across multiple networks. Both biological and topological evaluations on the alignment results of real datasets demonstrate our approach is promising and preferable against previous multiple alignment methods.

Alignment of virus-host protein-protein interaction networks by integer linear programming: SARS-CoV-2.

MotivationBeside socio-economic issues, coronavirus pandemic COVID-19, the infectious disease caused by the newly discovered coronavirus SARS-CoV-2, has caused a deep impact in the scientific community, that has considerably increased its effort to discover the infection strategies of the new virus. Among the extensive and crucial research that has been carried out in the last months, the analysis of the virus-host relationship plays an important role in drug discovery. Virus-host protein-protein interactions are the active agents in virus replication, and the analysis of virus-host protein-protein interaction networks is fundamental to the study of the virus-host relationship.ResultsWe have adapted and implemented a recent integer linear programming model for protein-protein interaction network alignment to virus-host networks, and obtained a consensus alignment of the SARS-CoV-1 and SARS-CoV-2 virus-host protein-protein interaction networks. Despite the lack of shared human proteins in these virus-host networks, and the low number of preserved virus-host interactions, the consensus alignment revealed aligned human proteins that share a function related to viral infection, as well as human proteins of high functional similarity that interact with SARS-CoV-1 and SARS-CoV-2 proteins, whose alignment would preserve these virus-host interactions.

MONACO: accurate biological network alignment through optimal neighborhood matching between focal nodes.

Alignment of protein-protein interaction networks can be used for the unsupervised prediction of functional modules, such as protein complexes and signaling pathways, that are conserved across different species. To date, various algorithms have been proposed for biological network alignment, many of which attempt to incorporate topological similarity between the networks into the alignment process with the goal of constructing accurate and biologically meaningful alignments. Especially, random walk models have been shown to be effective for quantifying the global topological relatedness between nodes that belong to different networks by diffusing node-level similarity along the interaction edges. However, these schemes are not ideal for capturing the local topological similarity between nodes. In this article, we propose MONACO, a novel and versatile network alignment algorithm that finds highly accurate pairwise and multiple network alignments through the iterative optimal matching of 'local' neighborhoods around focal nodes. Extensive performance assessment based on real networks as well as synthetic networks, for which the ground truth is known, demonstrates that MONACO clearly and consistently outperforms all other state-of-the-art network alignment algorithms that we have tested, in terms of accuracy, coherence and topological quality of the aligned network regions. Furthermore, despite the sharply enhanced alignment accuracy, MONACO remains computationally efficient and it scales well with increasing size and number of networks. Matlab implementation is freely available at https://github.com/bjyoontamu/MONACO. Supplementary data are available at Bioinformatics online.

Alignment of biological networks by integer linear programming: virus-host protein-protein interaction networks

BackgroundThe alignment of protein-protein interaction networks was recently formulated as an integer quadratic programming problem, along with a linearization that can be solved by integer linear programming software tools. However, the resulting integer linear program has a huge number of variables and constraints, rendering it of no practical use.ResultsWe present a compact integer linear programming reformulation of the protein-protein interaction network alignment problem, which can be solved using state-of-the-art mathematical modeling and integer linear programming software tools, along with empirical results showing that small biological networks, such as virus-host protein-protein interaction networks, can be aligned in a reasonable amount of time on a personal computer and the resulting alignments are structurally coherent and biologically meaningful.ConclusionsThe implementation of the integer linear programming reformulation using current mathematical modeling and integer linear programming software tools provided biologically meaningful alignments of virus-host protein-protein interaction networks.

AligNet: alignment of protein-protein interaction networks

BackgroundAll molecular functions and biological processes are carried out by groups of proteins that interact with each other. Metaproteomic data continuously generates new proteins whose molecular functions and relations must be discovered. A widely accepted structure to model functional relations between proteins are protein-protein interaction networks (PPIN), and their analysis and alignment has become a key ingredient in the study and prediction of protein-protein interactions, protein function, and evolutionary conserved assembly pathways of protein complexes. Several PPIN aligners have been proposed, but attaining the right balance between network topology and biological information is one of the most difficult and key points in the design of any PPIN alignment algorithm.ResultsMotivated by the challenge of well-balanced and efficient algorithms, we have designed and implemented AligNet, a parameter-free pairwise PPIN alignment algorithm aimed at bridging the gap between topologically efficient and biologically meaningful matchings. A comparison of the results obtained with AligNet and with the best aligners shows that AligNet achieves indeed a good balance between topological and biological matching.ConclusionIn this paper we present AligNet, a new pairwise global PPIN aligner that produces biologically meaningful alignments, by achieving a good balance between structural matching and protein function conservation, and more efficient computations than state-of-the-art tools.

MPGM: Scalable and Accurate Multiple Network Alignment.

Protein-protein interaction (PPI) network alignment is a canonical operation to transfer biological knowledge among species. The alignment of PPI-networks has many applications, such as the prediction of protein function, detection of conserved network motifs, and the reconstruction of species' phylogenetic relationships. A good multiple-network alignment (MNA), by considering the data related to several species, provides a deep understanding of biological networks and system-level cellular processes. With the massive amounts of available PPI data and the increasing number of known PPI networks, the problem of MNA is gaining more attention in the systems-biology studies. In this paper, we introduce a new scalable and accurate algorithm, called MPGM, for aligning multiple networks. The MPGM algorithm has two main steps: (i) SeedGeneration and (ii) MultiplePercolation. In the first step, to generate an initial set of seed tuples, the SeedGeneration algorithm uses only protein sequence similarities. In the second step, to align remaining unmatched nodes, the MultiplePercolation algorithm uses network structures and the seed tuples generated from the first step. We show that, with respect to different evaluation criteria, MPGM outperforms the other state-of-the-art algorithms. In addition, we guarantee the performance of MPGM under certain classes of network models. We introduce a sampling-based stochastic model for generating k correlated networks. We prove that for this model if a sufficient number of seed tuples are available, the MultiplePercolation algorithm correctly aligns almost all the nodes. Our theoretical results are supported by experimental evaluations over synthetic networks.

TANA: efficient approach for predicting protein functions from sequence homology and alignment of protein-protein interaction networks

TANA: efficient approach for predicting protein functions from sequence homology and alignment of protein-protein interaction networks

TANA: efficient approach for predicting protein functions from sequence homology and alignment of protein-protein interaction networks

TANA: efficient approach for predicting protein functions from sequence homology and alignment of protein-protein interaction networks

TANA: efficient approach for predicting protein functions from sequence homology and alignment of protein-protein interaction networks

TANA: efficient approach for predicting protein functions from sequence homology and alignment of protein-protein interaction networks

LePrimAlign: local entropy-based alignment of PPI networks to predict conserved modules

BackgroundCross-species analysis of protein-protein interaction (PPI) networks provides an effective means of detecting conserved interaction patterns. Identifying such conserved substructures between PPI networks of different species increases our understanding of the principles deriving evolution of cellular organizations and their functions in a system level. In recent years, network alignment techniques have been applied to genome-scale PPI networks to predict evolutionary conserved modules. Although a wide variety of network alignment algorithms have been introduced, developing a scalable local network alignment algorithm with high accuracy is still challenging.ResultsWe present a novel pairwise local network alignment algorithm, called LePrimAlign, to predict conserved modules between PPI networks of three different species. The proposed algorithm exploits the results of a pairwise global alignment algorithm with many-to-many node mapping. It also applies the concept of graph entropy to detect initial cluster pairs from two networks. Finally, the initial clusters are expanded to increase the local alignment score that is formulated by a combination of intra-network and inter-network scores. The performance comparison with state-of-the-art approaches demonstrates that the proposed algorithm outperforms in terms of accuracy of identified protein complexes and quality of alignments.ConclusionThe proposed method produces local network alignment of higher accuracy in predicting conserved modules even with large biological networks at a reduced computational cost.

Adaptive Large Neighborhood Search Enhances Global Network Alignment

Aligning protein-protein interaction networks from different species is a useful mechanism for figuring out orthologous proteins, predicting/verifying protein unknown functions or constructing evolutionary relationships. The network alignment problem is proved to be NP-hard, requiring exponential-time algorithms, which is not feasible for the fast growth of biological data. In this paper, we present a novel protein-protein interaction global network alignment algorithm, which is enhanced with an extended large neighborhood search heuristics. Evaluated on benchmark datasets of yeast, fly, human and worm, the proposed algorithm outperforms state-of-the-art. Furthermore, the complexity of ours is polynomial, thus being scalable to large biological networks in practice.
 Keywords
 Heuristic, Protein-protein interaction networks, network alignment, neighborhood search
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