Improving clustering with metabolic pathway data

Background: It is a common practice in bioinformatics to validate each group returned by a clustering algorithm through manual analysis, according to a-priori biological knowledge. This procedure helps finding functionally related patterns to propose hypotheses for their behavior and the biological processes involved. Therefore, this knowledge is used only as a second step, after data are just clustered according to their expression patterns. Thus, it could be very useful to be able to improve the clustering of biological data by incorporating prior knowledge into the cluster formation itself, in order to enhance the biological value of the clusters. Results: A novel training algorithm for clustering is presented, which evaluates the biological internal connections of the data points while the clusters are being formed. Within this training algorithm, the calculation of distances among data points and neurons centroids includes a new term based on information from well-known metabolic pathways. The standard self-organizing map (SOM) training versus the biologically-inspired SOM (bSOM) training were tested with two real data sets of transcripts and metabolites from Solanum lycopersicum and Arabidopsis thaliana species. Classical data mining validation measures were used to evaluate the clustering solutions obtained by both algorithms. Moreover, a new measure that takes into account the biological connectivity of the clusters was applied. The results of bSOM show important improvements in the convergence and performance for the proposed clustering method in comparison to standard SOM training, in particular, from the application point of view. Conclusions: Analyses of the clusters obtained with bSOM indicate that including biological information during training can certainly increase the biological value of the clusters found with the proposed method. It is worth to highlight that this fact has effectively improved the results, which can simplify their further analysis.Fil: Milone, Diego Humberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; ArgentinaFil: Stegmayer, Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; ArgentinaFil: Lopez, Mariana Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Carrari, Fernando Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentin

Seeing the Forest for the Trees: Using the Gene Ontology to Restructure Hierarchical Clustering

Motivation: There is a growing interest in improving the cluster analysis of expression data by incorporating into it prior knowledge, such as the Gene Ontology (GO) annotations of genes, in order to improve the biological relevance of the clusters that are subjected to subsequent scrutiny. The structure of the GO is another source of background knowledge that can be exploited through the use of semantic similarity. Results: We propose here a novel algorithm that integrates semantic similarities (derived from the ontology structure) into the procedure of deriving clusters from the dendrogram constructed during expression-based hierarchical clustering. Our approach can handle the multiple annotations, from different levels of the GO hierarchy, which most genes have. Moreover, it treats annotated and unannotated genes in a uniform manner. Consequently, the clusters obtained by our algorithm are characterized by significantly enriched annotations. In both cross-validation tests and when using an external index such as protein–protein interactions, our algorithm performs better than previous approaches. When applied to human cancer expression data, our algorithm identifies, among others, clusters of genes related to immune response and glucose metabolism. These clusters are also supported by protein–protein interaction data. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.Lynne and William Frankel Center for Computer Science; Paul Ivanier center for robotics research and production; National Institutes of Health (R01 HG003367-01A1

Techniques for clustering gene expression data

Many clustering techniques have been proposed for the analysis of gene expression data obtained from microarray experiments. However, choice of suitable method(s) for a given experimental dataset is not straightforward. Common approaches do not translate well and fail to take account of the data profile. This review paper surveys state of the art applications which recognises these limitations and implements procedures to overcome them. It provides a framework for the evaluation of clustering in gene expression analyses. The nature of microarray data is discussed briefly. Selected examples are presented for the clustering methods considered

Partial mixture model for tight clustering of gene expression time-course

Background: Tight clustering arose recently from a desire to obtain tighter and potentially more informative clusters in gene expression studies. Scattered genes with relatively loose correlations should be excluded from the clusters. However, in the literature there is little work dedicated to this area of research. On the other hand, there has been extensive use of maximum likelihood techniques for model parameter estimation. By contrast, the minimum distance estimator has been largely ignored. Results: In this paper we show the inherent robustness of the minimum distance estimator that makes it a powerful tool for parameter estimation in model-based time-course clustering. To apply minimum distance estimation, a partial mixture model that can naturally incorporate replicate information and allow scattered genes is formulated. We provide experimental results of simulated data fitting, where the minimum distance estimator demonstrates superior performance to the maximum likelihood estimator. Both biological and statistical validations are conducted on a simulated dataset and two real gene expression datasets. Our proposed partial regression clustering algorithm scores top in Gene Ontology driven evaluation, in comparison with four other popular clustering algorithms. Conclusion: For the first time partial mixture model is successfully extended to time-course data analysis. The robustness of our partial regression clustering algorithm proves the suitability of the ombination of both partial mixture model and minimum distance estimator in this field. We show that tight clustering not only is capable to generate more profound understanding of the dataset under study well in accordance to established biological knowledge, but also presents interesting new hypotheses during interpretation of clustering results. In particular, we provide biological evidences that scattered genes can be relevant and are interesting subjects for study, in contrast to prevailing opinion

Stable Feature Selection for Biomarker Discovery

Feature selection techniques have been used as the workhorse in biomarker discovery applications for a long time. Surprisingly, the stability of feature selection with respect to sampling variations has long been under-considered. It is only until recently that this issue has received more and more attention. In this article, we review existing stable feature selection methods for biomarker discovery using a generic hierarchal framework. We have two objectives: (1) providing an overview on this new yet fast growing topic for a convenient reference; (2) categorizing existing methods under an expandable framework for future research and development