42 research outputs found

    Finding Bicliques in Digraphs: Application into Viral-host Protein Interactome

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    We provide the first formalization true to the best of our knowledge to the problem of finding bicliques in a directed graph. The problem is addressed employing a two-stage approach based on an existing biclustering algorithm. This novel problem is useful in several biological applications of which we focus only on analyzing the viral-host protein interaction graphs. Strong and significant bicliques of HIV-1 and human proteins are derived using the proposed methodology, which provides insights into some novel regulatory functionalities in case of the acute immunodeficiency syndrome in human

    Nonnegative factorization and the maximum edge biclique problem

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    Nonnegative matrix factorization (NMF) is a data analysis technique based on the approximation of a nonnegative matrix with a product of two nonnegative factors, which allows compression and interpretation of nonnegative data. In this paper, we study the case of rank-one factorization and show that when the matrix to be factored is not required to be nonnegative, the corresponding problem (R1NF) becomes NP-hard. This sheds new light on the complexity of NMF since any algorithm for fixed-rank NMF must be able to solve at least implicitly such rank-one subproblems. Our proof relies on a reduction of the maximum edge biclique problem to R1NF. We also link stationary points of R1NF to feasible solutions of the biclique problem, which allows us to design a new type of biclique finding algorithm based on the application of a block-coordinate descent scheme to R1NF. We show that this algorithm, whose algorithmic complexity per iteration is proportional to the number of edges in the graph, is guaranteed to converge to a biclique and that it performs competitively with existing methods on random graphs and text mining datasets.nonnegative matrix factorization, rank-one factorization, maximum edge biclique problem, algorithmic complexity, biclique finding algorithm

    Multipartite Graph Algorithms for the Analysis of Heterogeneous Data

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    The explosive growth in the rate of data generation in recent years threatens to outpace the growth in computer power, motivating the need for new, scalable algorithms and big data analytic techniques. No field may be more emblematic of this data deluge than the life sciences, where technologies such as high-throughput mRNA arrays and next generation genome sequencing are routinely used to generate datasets of extreme scale. Data from experiments in genomics, transcriptomics, metabolomics and proteomics are continuously being added to existing repositories. A goal of exploratory analysis of such omics data is to illuminate the functions and relationships of biomolecules within an organism. This dissertation describes the design, implementation and application of graph algorithms, with the goal of seeking dense structure in data derived from omics experiments in order to detect latent associations between often heterogeneous entities, such as genes, diseases and phenotypes. Exact combinatorial solutions are developed and implemented, rather than relying on approximations or heuristics, even when problems are exceedingly large and/or difficult. Datasets on which the algorithms are applied include time series transcriptomic data from an experiment on the developing mouse cerebellum, gene expression data measuring acute ethanol response in the prefrontal cortex, and the analysis of a predicted protein-protein interaction network. A bipartite graph model is used to integrate heterogeneous data types, such as genes with phenotypes and microbes with mouse strains. The techniques are then extended to a multipartite algorithm to enumerate dense substructure in multipartite graphs, constructed using data from three or more heterogeneous sources, with applications to functional genomics. Several new theoretical results are given regarding multipartite graphs and the multipartite enumeration algorithm. In all cases, practical implementations are demonstrated to expand the frontier of computational feasibility

    Bi-(N-) cluster editing and its biomedical applications

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    The extremely fast advances in wet-lab techniques lead to an exponential growth of heterogeneous and unstructured biological data, posing a great challenge to data integration in nowadays system biology. The traditional clustering approach, although widely used to divide the data into groups sharing common features, is less powerful in the analysis of heterogeneous data from n different sources (n _ 2). The co-clustering approach has been widely used for combined analyses of multiple networks to address the challenge of heterogeneity. In this thesis, novel methods for the co-clustering of large scale heterogeneous data sets are presented in the software package n-CluE: one exact algorithm and two heuristic algorithms based on the model of bi-/n-cluster editing by modeling the input as n-partite graphs and solving the clustering problem with various strategies. In the first part of the thesis, the complexity and the fixed-parameter tractability of the extended bicluster editing model with relaxed constraints are investigated, namely the ?-bicluster editing model and its NP-hardness is proven. Based on the results of this analysis, three strategies within the n-CluE software package are then established and discussed, together with the evaluations on performances and the systematic comparisons against other algorithms of the same type in solving bi-/n-cluster editing problem. To demonstrate the practical impact, three real-world analyses using n-CluE are performed, including (a) prediction of novel genotype-phenotype associations by clustering the data from Genome-Wide Association Studies; (b) comparison between n-CluE and eight other biclustering tools on GEO Omnibus microarray data sets; (c) drug repositioning predictions by co-clustering on drug, gene and disease networks. The outstanding performance of n-CluE in the real-world applications shows its strength and flexibility in integrating heterogeneous data and extracting biological relevant information in bioinformatic analyses.Die enormen Fortschritte im Bereich Labortechnik haben in jĂŒngster Zeit zu einer exponentiell wachsenden Menge an heterogenen und unstrukturierten Daten gefĂŒhrt. Dies stellt eine große Herausforderung fĂŒr systembiologische Forschung dar, innerhalb derer diese Datenmengen durch Datenintegration und Datamining zusammengefasst und in Kombination analysiert werden. Traditionelles Clustering ist eine vielseitig eingesetzte Methode, um EntitĂ€ten innerhalb grosser Datenmengen bezĂŒglich ihrer Ähnlichkeit bestimmter Attribute zu gruppieren (“clustern„). Beim Clustern von heterogenen Daten aus n (n > 2) unterschiedlichen Quellen zeigen traditionelle Clusteringmethoden jedoch SchwĂ€chen. In solchen FĂ€llen bieten Co-clusteringmethoden dadurch Vorteile, dass sie DatensĂ€tze gleichzeitig partitionieren können. In dieser Dissertation stelle ich neue Clusteringmethoden vor, die in der Software n-CluE zusammengefĂŒhrt sind. Diese neuen Methoden wurden aus dem bi-/n-cluster editing heraus entwickelt und lösen durch Transformation der EingangsdatensĂ€tze in n-partite Graphen mit verschiedenen Strategien das zugrundeliegende Clusteringproblem. Diese Dissertation ist in zwei verschiedene Teile gegliedert. Der erste Teil befasst sich eingehend mit der KomplexitĂ€tanalyse verschiedener erweiterter bicluster editing Modelle, die sog. ?-bicluster editing Modelle und es wird der Beweis der NP-Schwere erbracht. Basierend auf diesen theoretischen Gesichtspunkten prĂ€sentiere ich im zweiten Teil drei unterschiedliche Algorithmen, einen exakten Algorithmus und zwei Heuristiken und demonstriere ihre LeistungsfĂ€higkeit und Robustheit im Vergleich mit anderen algorithmischen Herangehensweisen. Die StĂ€rken von n-CluE werden anhand von drei realen Anwendungsbeispielen untermauert: (a) Die Vorhersage neuartiger Genotyp-PhĂ€notyp-Assoziationen durch Biclustering-Analyse von Daten aus genomweiten Assoziationsstudien (GWAS);(b) Der Vergleich zwischen n-CluE und acht weiteren Softwarepaketen anhand von Bicluster-Analysen von Microarraydaten aus den Gene Expression Omnibus (GEO); (c) Die Vorhersage von Medikamenten-Repositionierung durch integrierte Analyse von Medikamenten-, Gen- und Krankeitsnetzwerken. Die Resultate zeigen eindrucksvoll die StĂ€rken der n-CluE Software. Das Ergebnis ist eine leistungsstarke, robuste und flexibel erweiterbare Implementierung des Biclustering-Theorems zur Integration grosser heterogener Datenmengen fĂŒr das Extrahieren biologisch relevanter Ergebnisse im Rahmen von bioinformatischen Studien

    In-silico identification of phenotype-biased functional modules

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    <p>Abstract</p> <p>Background</p> <p>Phenotypes exhibited by microorganisms can be useful for several purposes, e.g., ethanol as an alternate fuel. Sometimes, the target phenotype maybe required in combination with other phenotypes, in order to be useful, for e.g., an industrial process may require that the organism survive in an anaerobic, alcohol rich environment and be able to feed on both hexose and pentose sugars to produce ethanol. This combination of traits may not be available in any existing organism or if they do exist, the mechanisms involved in the phenotype-expression may not be efficient enough to be useful. Thus, it may be required to genetically modify microorganisms. However, before any genetic modification can take place, it is important to identify the underlying cellular subsystems responsible for the expression of the target phenotype.</p> <p>Results</p> <p>In this paper, we develop a method to identify statistically significant and phenotypically-biased functional modules. The method can compare the organismal network information from hundreds of phenotype expressing and phenotype non-expressing organisms to identify cellular subsystems that are more prone to occur in phenotype-expressing organisms than in phenotype non-expressing organisms. We have provided literature evidence that the phenotype-biased modules identified for phenotypes such as hydrogen production (dark and light fermentation), respiration, gram-positive, gram-negative and motility, are indeed phenotype-related.</p> <p>Conclusion</p> <p>Thus we have proposed a methodology to identify phenotype-biased cellular subsystems. We have shown the effectiveness of our methodology by applying it to several target phenotypes. The code and all supplemental files can be downloaded from (<url>http://freescience.org/cs/phenotype-biased-biclusters/</url>).</p

    Quantum Algorithm for Maximum Biclique Problem

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    Identifying a biclique with the maximum number of edges bears considerable implications for numerous fields of application, such as detecting anomalies in E-commerce transactions, discerning protein-protein interactions in biology, and refining the efficacy of social network recommendation algorithms. However, the inherent NP-hardness of this problem significantly complicates the matter. The prohibitive time complexity of existing algorithms is the primary bottleneck constraining the application scenarios. Aiming to address this challenge, we present an unprecedented exploration of a quantum computing approach. Efficient quantum algorithms, as a crucial future direction for handling NP-hard problems, are presently under intensive investigation, of which the potential has already been proven in practical arenas such as cybersecurity. However, in the field of quantum algorithms for graph databases, little work has been done due to the challenges presented by the quantum representation of complex graph topologies. In this study, we delve into the intricacies of encoding a bipartite graph on a quantum computer. Given a bipartite graph with n vertices, we propose a ground-breaking algorithm qMBS with time complexity O^*(2^(n/2)), illustrating a quadratic speed-up in terms of complexity compared to the state-of-the-art. Furthermore, we detail two variants tailored for the maximum vertex biclique problem and the maximum balanced biclique problem. To corroborate the practical performance and efficacy of our proposed algorithms, we have conducted proof-of-principle experiments utilizing IBM quantum simulators, of which the results provide a substantial validation of our approach to the extent possible to date

    A Novel Biclustering Approach to Association Rule Mining for Predicting HIV-1–Human Protein Interactions

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    Identification of potential viral-host protein interactions is a vital and useful approach towards development of new drugs targeting those interactions. In recent days, computational tools are being utilized for predicting viral-host interactions. Recently a database containing records of experimentally validated interactions between a set of HIV-1 proteins and a set of human proteins has been published. The problem of predicting new interactions based on this database is usually posed as a classification problem. However, posing the problem as a classification one suffers from the lack of biologically validated negative interactions. Therefore it will be beneficial to use the existing database for predicting new viral-host interactions without the need of negative samples. Motivated by this, in this article, the HIV-1–human protein interaction database has been analyzed using association rule mining. The main objective is to identify a set of association rules both among the HIV-1 proteins and among the human proteins, and use these rules for predicting new interactions. In this regard, a novel association rule mining technique based on biclustering has been proposed for discovering frequent closed itemsets followed by the association rules from the adjacency matrix of the HIV-1–human interaction network. Novel HIV-1–human interactions have been predicted based on the discovered association rules and tested for biological significance. For validation of the predicted new interactions, gene ontology-based and pathway-based studies have been performed. These studies show that the human proteins which are predicted to interact with a particular viral protein share many common biological activities. Moreover, literature survey has been used for validation purpose to identify some predicted interactions that are already validated experimentally but not present in the database. Comparison with other prediction methods is also discussed

    Biclustering analysis of transcriptome big data identifies condition-specific microRNA targets

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    We present a novel approach to identify human microRNA (miRNA) regulatory modules (mRNA targets and relevant cell conditions) by biclustering a large collection of mRNA fold-change data for sequence-specific targets. Bicluster targets were assessed using validated messenger RNA (mRNA) targets and exhibited on an average 17.0% (median 19.4%) improved gain in certainty (sensitivity + specificity). The net gain was further increased up to 32.0% (median 33.4%) by incorporating functional networks of targets. We analyzed cancer-specific biclusters and found that the PI3K/Akt signaling pathway is strongly enriched with targets of a few miRNAs in breast cancer and diffuse large B-cell lymphoma. Indeed, five independent prognostic miRNAs were identified, and repression of bicluster targets and pathway activity by miR-29 was experimentally validated. In total, 29 898 biclusters for 459 human miRNAs were collected in the BiMIR database where biclusters are searchable for miRNAs, tissues, diseases, keywords and target genes
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