Juan A. Nepomuceno

Biclustering of Gene Expression Data by Correlation-Based Scatter Search

BackgroundThe analysis of data generated by microarray technology is very useful to understand how the genetic information becomes functional gene products. Biclustering algorithms can determine a group of genes which are co-expressed under a set of experimental conditions. Recently, new biclustering methods based on metaheuristics have been proposed. Most of them use the Mean Squared Residue as merit function but interesting and relevant patterns from a biological point of view such as shifting and scaling patterns may not be detected using this measure. However, it is important to discover this type of patterns since commonly the genes can present a similar behavior although their expression levels vary in different ranges or magnitudes.MethodsScatter Search is an evolutionary technique that is based on the evolution of a small set of solutions which are chosen according to quality and diversity criteria. This paper presents a Scatter Search with the aim of finding biclusters from gene expression data. In this algorithm the proposed fitness function is based on the linear correlation among genes to detect shifting and scaling patterns from genes and an improvement method is included in order to select just positively correlated genes.ResultsThe proposed algorithm has been tested with three real data sets such as Yeast Cell Cycle dataset, human B-cells lymphoma dataset and Yeast Stress dataset, finding a remarkable number of biclusters with shifting and scaling patterns. In addition, the performance of the proposed method and fitness function are compared to that of CC, OPSM, ISA, BiMax, xMotifs and Samba using Gene the Ontology Database.

Integrating biological knowledge based on functional annotations for biclustering of gene expression data

Gene expression data analysis is based on the assumption that co-expressed genes imply co-regulated genes. This assumption is being reformulated because the co-expression of a group of genes may be the result of an independent activation with respect to the same experimental condition and not due to the same regulatory regime. For this reason, traditional techniques are recently being improved with the use of prior biological knowledge from open-access repositories together with gene expression data. Biclustering is an unsupervised machine learning technique that searches patterns in gene expression data matrices. A scatter search-based biclustering algorithm that integrates biological information is proposed in this paper. In addition to the gene expression data matrix, the input of the algorithm is only a direct annotation file that relates each gene to a set of terms from a biological repository where genes are annotated. Two different biological measures, FracGO and SimNTO, are proposed to integrate this information by means of its addition to-be-optimized fitness function in the scatter search scheme. The measure FracGO is based on the biological enrichment and SimNTO is based on the overlapping among GO annotations of pairs of genes. Experimental results evaluate the proposed algorithm for two datasets and show the algorithm performs better when biological knowledge is integrated. Moreover, the analysis and comparison between the two different biological measures is presented and it is concluded that the differences depend on both the data source and how the annotation file has been built in the case GO is used. It is also shown that the proposed algorithm obtains a greater number of enriched biclusters than other classical biclustering algorithms typically used as benchmark and an analysis of the overlapping among biclusters reveals that the biclusters obtained present a low overlapping. The proposed methodology is a general-purpose algorithm which allows the integration of biological information from several sources and can be extended to other biclustering algorithms based on the optimization of a merit function.

Evolutionary metaheuristic for biclustering based on linear correlations among genes

A new measure to evaluate the quality of a bicluster is proposed in this paper. This measure is based on correlations among genes. Moreover, a new evolutionary metaheuristic based on Scatter Search, which uses this measure as the fitness function, is presented to obtain biclusters that contain groups de highly-correlated genes. Later, an analysis of the correlation matrix of these biclusters is made to select these groups of genes that define new biclusters with shifting and scaling patterns. Experimental results from human Bcell lymphoma are presented.

Biclusters evaluation based on shifting and scaling patterns

Microarray techniques have motivated the develop of different methods to extract useful information from a biological point of view. Biclustering algorithms obtain a set of genes with the same behaviour over a group of experimental conditions from gene expression data. In order to evaluate the quality of a bicluster, it is useful to identify specific tendencies represented by patterns on data. These patterns describe the behaviour of a bicluster obtained previously by an adequate biclustering technique from gene expression data. In this paper a new measure for evaluating biclusters is proposed. This measure captures a special kind of patterns with scaling trends which represents quality patterns. They are not contemplated with the previous evaluating measure accepted in the literature. This work is a first step to investigate methods that search biclusters based on the concept of shift and scale invariance. Experimental results based on the yeast cell cycle and the human B-cell lymphoma datasets are reported. Finally, the performance of the proposed technique is compared with an optimization method based on the Nelder-Mead Simplex search algorithm.

A Hybrid Metaheuristic for Biclustering Based on Scatter Search and Genetic Algorithms

In this paper a hybrid metaheuristic for biclustering based on Scatter Search and Genetic Algorithms is presented. A general scheme of Scatter Search has been used to obtain high---quality biclusters, but a way of generating the initial population and a method of combination based on Genetic Algorithms have been chosen. Experimental results from yeast cell cycle and human B-cell lymphoma are reported. Finally, the performance of the proposed hybrid algorithm is compared with a genetic algorithm recently published.

Scatter search-based identification of local patterns with positive and negative correlations in gene expression data

Graphical abstractDisplay Omitted HighlightsBiclustering of gene expression data.Scatter search metaheuristic.Correlation-based merit function.Positive and negative correlations among genes.Comparison is based on a priori biological information. This paper presents a scatter search approach based on linear correlations among genes to find biclusters, which include both shifting and scaling patterns and negatively correlated patterns contrarily to most of correlation-based algorithms published in the literature. The methodology established here for comparison is based on a priori biological information stored in the well-known repository Gene Ontology (GO). In particular, the three existing categories in GO, Biological Process, Cellular Components and Molecular Function, have been used. The performance of the proposed algorithm has been compared to other benchmark biclustering algorithms, specifically a group of classical biclustering algorithms and two algorithms that use correlation-based merit functions. The proposed algorithm outperforms the benchmark algorithms and finds patterns based on negative correlations. Although these patterns contain important relationship among genes, they are not found by most of biclustering algorithms. The experimental study also shows the importance of the size in a bicluster in addition to the value of its correlation. In particular, the size of a bicluster has an influence over its enrichment in a GO term.

Correlation–based scatter search for discovering biclusters from gene expression data

Scatter Search is an evolutionary method that combines existing solutions to create new offspring as the well–known genetic algorithms. This paper presents a Scatter Search with the aim of finding biclusters from gene expression data. However, biclusters with certain patterns are more interesting from a biological point of view. Therefore, the proposed Scatter Search uses a measure based on linear correlations among genes to evaluate the quality of biclusters. As it is usual in Scatter Search methodology an improvement method is included which avoids to find biclusters with negatively correlated genes. Experimental results from yeast cell cycle and human B-cell lymphoma datasets are reported showing a remarkable performance of the proposed method and measure.

An Overlapping ControlBiclustering Algorithm from Gene Expression Data

In this paper a hybrid metaheuristic for biclustering based on Scatter Search and Genetic Algorithms is presented. A general scheme of Scatter Search has been used to obtain high--quality biclusters, but a way of generating the initial population and a method of combination based on Genetic Algorithms have been chosen. Moreover, in the own algorithm the overlapping among biclusters is controlled adding a penalization term in the fitness function. Experimental results from yeast cell cycle are reported. Finally, the performance of the proposed hybrid algorithm is compared with a genetic algorithm recently published.

Feature selection based on bootstrapping

The results of feature selection methods have a great influence on the success of data mining processes, especially when the data sets have high dimensionality. In order to find the optimal result from feature selection methods, we should check each possible subset of features to obtain the precision on classification, i.e., an exhaustive search through the search space. However, it is an unfeasible task due to its computational complexity. In this paper, we propose a novel method of feature selection based on bootstrapping techniques. Our approach shows that it is not necessary to try every subset of features, but only a very small subset of combinations to achieve the same performance as the exhaustive approach. The experiments have been carried out using very high-dimensional datasets (thousands of features) and they show that it is possible to maintain the precision at the same time that the complexity is reduced substantially

Biclustering of Gene Expression Data Based on SimUI Semantic Similarity Measure

Biclustering is an unsupervised machine learning technique that simultaneously clusters genes and conditions in gene expression data. Gene Ontology (GO) is usually used in this context to validate the biological relevance of the results. However, although the integration of biological information from different sources is one of the research directions in Bioinformatics, GO is not used in biclustering as an input data. A scatter search-based algorithm that integrates GO information during the biclustering search process is presented in this paper. SimUI is a GO semantic similarity measure that defines a distance between two genes. The algorithm optimizes a fitness function that uses SimUI to integrate the biological information stored in GO. Experimental results analyze the effect of integration of the biological information through this measure. A SimUI fitness function configuration is experimentally studied in a scatter search-based biclustering algorithm.