Effect of data normalization on fuzzy clustering of DNA microarray data

BACKGROUND: Microarray technology has made it possible to simultaneously measure the expression levels of large numbers of genes in a short time. Gene expression data is information rich; however, extensive data mining is required to identify the patterns that characterize the underlying mechanisms of action. Clustering is an important tool for finding groups of genes with similar expression patterns in microarray data analysis. However, hard clustering methods, which assign each gene exactly to one cluster, are poorly suited to the analysis of microarray datasets because in such datasets the clusters of genes frequently overlap. RESULTS: In this study we applied the fuzzy partitional clustering method known as Fuzzy C-Means (FCM) to overcome the limitations of hard clustering. To identify the effect of data normalization, we used three normalization methods, the two common scale and location transformations and Lowess normalization methods, to normalize three microarray datasets and three simulated datasets. First we determined the optimal parameters for FCM clustering. We found that the optimal fuzzification parameter in the FCM analysis of a microarray dataset depended on the normalization method applied to the dataset during preprocessing. We additionally evaluated the effect of normalization of noisy datasets on the results obtained when hard clustering or FCM clustering was applied to those datasets. The effects of normalization were evaluated using both simulated datasets and microarray datasets. A comparative analysis showed that the clustering results depended on the normalization method used and the noisiness of the data. In particular, the selection of the fuzzification parameter value for the FCM method was sensitive to the normalization method used for datasets with large variations across samples. CONCLUSION: Lowess normalization is more robust for clustering of genes from general microarray data than the two common scale and location adjustment methods when samples have varying expression patterns or are noisy. In particular, the FCM method slightly outperformed the hard clustering methods when the expression patterns of genes overlapped and was advantageous in finding co-regulated genes. Thus, the FCM approach offers a convenient method for finding subsets of genes that are strongly associated to a given cluster

FLAME, a novel fuzzy clustering method for the analysis of DNA microarray data

BACKGROUND: Data clustering analysis has been extensively applied to extract information from gene expression profiles obtained with DNA microarrays. To this aim, existing clustering approaches, mainly developed in computer science, have been adapted to microarray data analysis. However, previous studies revealed that microarray datasets have very diverse structures, some of which may not be correctly captured by current clustering methods. We therefore approached the problem from a new starting point, and developed a clustering algorithm designed to capture dataset-specific structures at the beginning of the process. RESULTS: The clustering algorithm is named Fuzzy clustering by Local Approximation of MEmbership (FLAME). Distinctive elements of FLAME are: (i) definition of the neighborhood of each object (gene or sample) and identification of objects with "archetypal" features named Cluster Supporting Objects, around which to construct the clusters; (ii) assignment to each object of a fuzzy membership vector approximated from the memberships of its neighboring objects, by an iterative converging process in which membership spreads from the Cluster Supporting Objects through their neighbors. Comparative analysis with K-means, hierarchical, fuzzy C-means and fuzzy self-organizing maps (SOM) showed that data partitions generated by FLAME are not superimposable to those of other methods and, although different types of datasets are better partitioned by different algorithms, FLAME displays the best overall performance. FLAME is implemented, together with all the above-mentioned algorithms, in a C++ software with graphical interface for Linux and Windows, capable of handling very large datasets, named Gene Expression Data Analysis Studio (GEDAS), freely available under GNU General Public License. CONCLUSION: The FLAME algorithm has intrinsic advantages, such as the ability to capture non-linear relationships and non-globular clusters, the automated definition of the number of clusters, and the identification of cluster outliers, i.e. genes that are not assigned to any cluster. As a result, clusters are more internally homogeneous and more diverse from each other, and provide better partitioning of biological functions. The clustering algorithm can be easily extended to applications different from gene expression analysis

FPF-SB: a Scalable Algorithm for Microarray Gene Expression Data Clustering

Efficient and effective analysis of large datasets from microarray gene expression data is one of the keys to time-critical personalized medicine. The issue we address here is the scalability of the data processing software for clustering gene expression data into groups with homogeneous expression profile. In this paper we propose /FPF-SB/, a novel clustering algorithm based on a combination of the Furthest-Point-First (FPF) heuristic for solving the /k/-center problem and a stability-based method for determining the number of clusters /k/. Our algorithm improves the state of the art: it is scalable to large datasets without sacrificing output quality

Fuzzy Logic in Medicine and Bioinformatics

The purpose of this paper is to present a general view of the current applications of fuzzy logic in medicine and bioinformatics. We particularly review the medical literature using fuzzy logic. We then recall the geometrical interpretation of fuzzy sets as points in a fuzzy hypercube and present two concrete illustrations in medicine (drug addictions) and in bioinformatics (comparison of genomes)

Memetic micro-genetic algorithms for cancer data classification

Fast and precise medical diagnosis of human cancer is crucial for treatment decisions. Gene selection consists of identifying a set of informative genes from microarray data to allow high predictive accuracy in human cancer classification. This task is a combinatorial search problem, and optimisation methods can be applied for its resolution. In this paper, two memetic micro-genetic algorithms (MμV1 and MμV2) with different hybridisation approaches are proposed for feature selection of cancer microarray data. Seven gene expression datasets are used for experimentation. The comparison with stochastic state-of-the-art optimisation techniques concludes that problem-dependent local search methods combined with micro-genetic algorithms improve feature selection of cancer microarray data.Fil: Rojas, Matias Gabriel. Universidad Nacional de Lujan. Centro de Investigacion Docencia y Extension En Tecnologias de la Informacion y Las Comunicaciones.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Olivera, Ana Carolina. Universidad Nacional de Cuyo. Facultad de Ingeniería; Argentina. Universidad Nacional de Lujan. Centro de Investigacion Docencia y Extension En Tecnologias de la Informacion y Las Comunicaciones.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Carballido, Jessica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Vidal, Pablo Javier. Universidad Nacional de Cuyo. Facultad de Ingeniería; Argentina. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentin

K-Boost: a Scalable Algorithm for High-Quality Clustering of Microarray Gene Expression Data

Motivation: Microarray technology for profiling gene expression levels is a popular tool in modern biological research. Applications range from tissue classification to the detection of metabolic networks, from drug discovery to time-critical personalized medicine. Given the increase in size and complexity of the data sets produced, their analysis is becoming problematic in terms of time/quality tradeoffs. Clustering genes with similar expression profiles is a key initial step for subsequent manipulations and the increasing volumes of data to be analyzed requires methods that are at the same time efficient (completing an analysis in minutes rather than hours) and effective (identifying significant clusters with high biological correlations). Results: In this paper we propose K-Boost, a novel clustering algorithm based on a combination of the Furthest-Point-First (FPF) heuristic for solving the metric k-centers problem, a stability-based method for determining the number of clusters (i.e. the value of k), and a k-means-like cluster refinement. K-Boost is able to detect the optimal number of clusters to produce. It is scalable to large data-sets without sacrificing output quality as measured by several internal and external criteria

A parallel genetic algorithm for single class pattern classification and its application for gene expression profiling in Streptomyces coelicolor

BACKGROUND: Identification of coordinately regulated genes according to the level of their expression during the time course of a process allows for discovering functional relationships among genes involved in the process. RESULTS: We present a single class classification method for the identification of genes of similar function from a gene expression time series. It is based on a parallel genetic algorithm which is a supervised computer learning method exploiting prior knowledge of gene function to identify unknown genes of similar function from expression data. The algorithm was tested with a set of randomly generated patterns; the results were compared with seven other classification algorithms including support vector machines. The algorithm avoids several problems associated with unsupervised clustering methods, and it shows better performance then the other algorithms. The algorithm was applied to the identification of secondary metabolite gene clusters of the antibiotic-producing eubacterium Streptomyces coelicolor. The algorithm also identified pathways associated with transport of the secondary metabolites out of the cell. We used the method for the prediction of the functional role of particular ORFs based on the expression data. CONCLUSION: Through analysis of a time series of gene expression, the algorithm identifies pathways which are directly or indirectly associated with genes of interest, and which are active during the time course of the experiment

Fuzzy clustering with entropy regularization for interval-valued data with an application to scientific journal citations

In recent years, the research of statistical methods to analyze complex structures of data has increased. In particular, a lot of attention has been focused on the interval-valued data. In a classical cluster analysis framework, an interesting line of research has focused on the clustering of interval-valued data based on fuzzy approaches. Following the partitioning around medoids fuzzy approach research line, a new fuzzy clustering model for interval-valued data is suggested. In particular, we propose a new model based on the use of the entropy as a regularization function in the fuzzy clustering criterion. The model uses a robust weighted dissimilarity measure to smooth noisy data and weigh the center and radius components of the interval-valued data, respectively. To show the good performances of the proposed clustering model, we provide a simulation study and an application to the clustering of scientific journals in research evaluation