426 research outputs found

    Analysis of Genetic Interaction Maps Reveals Functional Pleiotropy

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    Epistatic or genetic interactions, representing the effects of mutations on the phenotypes caused by other mutations, can be very helpful for uncovering functional relationships between genes. Recently, the Epistasis Miniarray Profile (E-MAP) method has emerged as a powerful approach for identifying such interactions systematically. As part of this approach, hierarchical clustering is used to partition genes into groups on the basis of the similarity between their global interaction profiles. Here we present an original biclustering algorithm for identifying groups of functionally related genes from E-MAP data in a manner that allows individual genes to be assigned to more than one functional group. This enables investigation of the pleiotropic nature of gene function, a goal that cannot be achieved with hierarchical clustering. The performance of our algorithm is illustrated by applying it to two E-MAP datasets and an E-MAP-like in silico dataset for the yeast S. cerevisiae. In addition to identifying the majority of the functional modules reported in these studies, our algorithm uncovers many recently documented and novel multi-functional relationships between genes and gene groups

    Minimax Structured Normal Means Inference

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    We provide a unified treatment of a broad class of noisy structure recovery problems, known as structured normal means problems. In this setting, the goal is to identify, from a finite collection of Gaussian distributions with different means, the distribution that produced some observed data. Recent work has studied several special cases including sparse vectors, biclusters, and graph-based structures. We establish nearly matching upper and lower bounds on the minimax probability of error for any structured normal means problem, and we derive an optimality certificate for the maximum likelihood estimator, which can be applied to many instantiations. We also consider an experimental design setting, where we generalize our minimax bounds and derive an algorithm for computing a design strategy with a certain optimality property. We show that our results give tight minimax bounds for many structure recovery problems and consider some consequences for interactive sampling

    Application Oriented Analysis of Large Scale Datasets

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    Diverse application areas, such as social network, epidemiology, and software engineering consist of systems of objects and their relationships. Such systems are generally modeled as graphs. Graphs consist of vertices that represent the objects, and edges that represent the relationships between them. These systems are data intensive and it is important to correctly analyze the data to obtain meaningful information. Combinatorial metrics can provide useful insights for analyzing these systems. In this thesis, we use the graph based metrics such as betweenness centrality, clustering coefficient, articulation points, etc. for analyzing instances of large change in evolving networks (Software Engineering), and identifying points of similarity (Gene Expression Data). Computations of combinatorial properties are expensive and most real world networks are not static. As the network evolves these properties have to be recomputed. In the last part of thesis, we develop a fast algorithm that avoids redundant recomputations of communities in dynamic networks

    Fine-grained parallelization of fitness functions in bioinformatics optimization problems: gene selection for cancer classification and biclustering of gene expression data

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    ANTECEDENTES: las metaheurísticas se utilizan ampliamente para resolver grandes problemas de optimización combinatoria en bioinformática debido al enorme conjunto de posibles soluciones. Dos problemas representativos son la selección de genes para la clasificación del cáncer y el agrupamiento de los datos de expresión génica. En la mayoría de los casos, estas metaheurísticas, así como otras técnicas no lineales, aplican una función de adecuación a cada solución posible con una población de tamaño limitado, y ese paso involucra latencias más altas que otras partes de los algoritmos, lo cual es la razón por la cual el tiempo de ejecución de las aplicaciones dependerá principalmente del tiempo de ejecución de la función de aptitud. Además, es habitual encontrar formulaciones aritméticas de punto flotante para las funciones de fitness. De esta manera, una paralelización cuidadosa de estas funciones utilizando la tecnología de hardware reconfigurable acelerará el cálculo, especialmente si se aplican en paralelo a varias soluciones de la población. RESULTADOS: una paralelización de grano fino de dos funciones de aptitud de punto flotante de diferentes complejidades y características involucradas en el biclustering de los datos de expresión génica y la selección de genes para la clasificación del cáncer permitió obtener mayores aceleraciones y cómputos de potencia reducida con respecto a los microprocesadores habituales. CONCLUSIONES: Los resultados muestran mejores rendimientos utilizando tecnología de hardware reconfigurable en lugar de los microprocesadores habituales, en términos de tiempo de consumo y consumo de energía, no solo debido a la paralelización de las operaciones aritméticas, sino también gracias a la evaluación de aptitud concurrente para varios individuos de la población en La metaheurística. Esta es una buena base para crear soluciones aceleradas y de bajo consumo de energía para escenarios informáticos intensivos.BACKGROUND: Metaheuristics are widely used to solve large combinatorial optimization problems in bioinformatics because of the huge set of possible solutions. Two representative problems are gene selection for cancer classification and biclustering of gene expression data. In most cases, these metaheuristics, as well as other non-linear techniques, apply a fitness function to each possible solution with a size-limited population, and that step involves higher latencies than other parts of the algorithms, which is the reason why the execution time of the applications will mainly depend on the execution time of the fitness function. In addition, it is usual to find floating-point arithmetic formulations for the fitness functions. This way, a careful parallelization of these functions using the reconfigurable hardware technology will accelerate the computation, specially if they are applied in parallel to several solutions of the population. RESULTS: A fine-grained parallelization of two floating-point fitness functions of different complexities and features involved in biclustering of gene expression data and gene selection for cancer classification allowed for obtaining higher speedups and power-reduced computation with regard to usual microprocessors. CONCLUSIONS: The results show better performances using reconfigurable hardware technology instead of usual microprocessors, in computing time and power consumption terms, not only because of the parallelization of the arithmetic operations, but also thanks to the concurrent fitness evaluation for several individuals of the population in the metaheuristic. This is a good basis for building accelerated and low-energy solutions for intensive computing scenarios.• Ministerio de Economía y Competitividad y Fondos FEDER. Contrato TIN2012-30685 (I+D+i) • Gobierno de Extremadura. Ayuda GR15011 para grupos TIC015 • CONICYT/FONDECYT/REGULAR/1160455. Beca para Ricardo Soto Guzmán • CONICYT/FONDECYT/REGULAR/1140897. Beca para Broderick CrawfordpeerReviewe

    Guaranteed clustering and biclustering via semidefinite programming

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    Identifying clusters of similar objects in data plays a significant role in a wide range of applications. As a model problem for clustering, we consider the densest k-disjoint-clique problem, whose goal is to identify the collection of k disjoint cliques of a given weighted complete graph maximizing the sum of the densities of the complete subgraphs induced by these cliques. In this paper, we establish conditions ensuring exact recovery of the densest k cliques of a given graph from the optimal solution of a particular semidefinite program. In particular, the semidefinite relaxation is exact for input graphs corresponding to data consisting of k large, distinct clusters and a smaller number of outliers. This approach also yields a semidefinite relaxation for the biclustering problem with similar recovery guarantees. Given a set of objects and a set of features exhibited by these objects, biclustering seeks to simultaneously group the objects and features according to their expression levels. This problem may be posed as partitioning the nodes of a weighted bipartite complete graph such that the sum of the densities of the resulting bipartite complete subgraphs is maximized. As in our analysis of the densest k-disjoint-clique problem, we show that the correct partition of the objects and features can be recovered from the optimal solution of a semidefinite program in the case that the given data consists of several disjoint sets of objects exhibiting similar features. Empirical evidence from numerical experiments supporting these theoretical guarantees is also provided

    A biclustering algorithm based on a Bicluster Enumeration Tree: application to DNA microarray data

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    <p>Abstract</p> <p>Background</p> <p>In a number of domains, like in DNA microarray data analysis, we need to cluster simultaneously rows (genes) and columns (conditions) of a data matrix to identify groups of rows coherent with groups of columns. This kind of clustering is called <it>biclustering</it>. Biclustering algorithms are extensively used in DNA microarray data analysis. More effective biclustering algorithms are highly desirable and needed.</p> <p>Methods</p> <p>We introduce <it>BiMine</it>, a new enumeration algorithm for biclustering of DNA microarray data. The proposed algorithm is based on three original features. First, <it>BiMine </it>relies on a new evaluation function called <it>Average Spearman's rho </it>(ASR). Second, <it>BiMine </it>uses a new tree structure, called <it>Bicluster Enumeration Tree </it>(BET), to represent the different biclusters discovered during the enumeration process. Third, to avoid the combinatorial explosion of the search tree, <it>BiMine </it>introduces a parametric rule that allows the enumeration process to cut tree branches that cannot lead to good biclusters.</p> <p>Results</p> <p>The performance of the proposed algorithm is assessed using both synthetic and real DNA microarray data. The experimental results show that <it>BiMine </it>competes well with several other biclustering methods. Moreover, we test the biological significance using a gene annotation web-tool to show that our proposed method is able to produce biologically relevant biclusters. The software is available upon request from the authors to academic users.</p
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