Dataset Information

Extracting regulatory modules from gene expression data by sequential pattern mining.

ABSTRACT: BACKGROUND: Identifying a regulatory module (RM), a bi-set of co-regulated genes and co-regulating conditions (or samples), has been an important challenge in functional genomics and bioinformatics. Given a microarray gene-expression matrix, biclustering has been the most common method for extracting RMs. Among biclustering methods, order-preserving biclustering by a sequential pattern mining technique has native advantage over the conventional biclustering approaches since it preserves the order of genes (or conditions) according to the magnitude of the expression value. However, previous sequential pattern mining-based biclustering has several weak points in that they can easily be computationally intractable in the real-size of microarray data and sensitive to inherent noise in the expression value. RESULTS: In this paper, we propose a novel sequential pattern mining algorithm that is scalable in the size of microarray data and robust with respect to noise. When applied to the microarray data of yeast, the proposed algorithm successfully found long order-preserving patterns, which are biologically significant but cannot be found in randomly shuffled data. The resulting patterns are well enriched to known annotations and are consistent with known biological knowledge. Furthermore, RMs as well as inter-module relations were inferred from the biologically significant patterns. CONCLUSIONS: Our approach for identifying RMs could be valuable for systematically revealing the mechanism of gene regulation at a genome-wide level.

SUBMITTER: Kim M

PROVIDER: S-EPMC3333188 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Extracting regulatory modules from gene expression data by sequential pattern mining.

Kim Mingoo M Shin Hyunjung H Su Chung Tae T Joung Je-Gun JG Kim Ju Han JH

BMC genomics 20111130

<h4>Background</h4>Identifying a regulatory module (RM), a bi-set of co-regulated genes and co-regulating conditions (or samples), has been an important challenge in functional genomics and bioinformatics. Given a microarray gene-expression matrix, biclustering has been the most common method for extracting RMs. Among biclustering methods, order-preserving biclustering by a sequential pattern mining technique has native advantage over the conventional biclustering approaches since it preserves t ...[more]

PMID: 22369275

Similar Datasets

Project description:BACKGROUND: Compendia of gene expression profiles under chemical and genetic perturbations constitute an invaluable resource from a systems biology perspective. However, the perturbational nature of such data imposes specific challenges on the computational methods used to analyze them. In particular, traditional clustering algorithms have difficulties in handling one of the prominent features of perturbational compendia, namely partial coexpression relationships between genes. Biclustering methods on the other hand are specifically designed to capture such partial coexpression patterns, but they show a variety of other drawbacks. For instance, some biclustering methods are less suited to identify overlapping biclusters, while others generate highly redundant biclusters. Also, none of the existing biclustering tools takes advantage of the staple of perturbational expression data analysis: the identification of differentially expressed genes. RESULTS: We introduce a novel method, called ENIGMA, that addresses some of these issues. ENIGMA leverages differential expression analysis results to extract expression modules from perturbational gene expression data. The core parameters of the ENIGMA clustering procedure are automatically optimized to reduce the redundancy between modules. In contrast to the biclusters produced by most other methods, ENIGMA modules may show internal substructure, i.e. subsets of genes with distinct but significantly related expression patterns. The grouping of these (often functionally) related patterns in one module greatly aids in the biological interpretation of the data. We show that ENIGMA outperforms other methods on artificial datasets, using a quality criterion that, unlike other criteria, can be used for algorithms that generate overlapping clusters and that can be modified to take redundancy between clusters into account. Finally, we apply ENIGMA to the Rosetta compendium of expression profiles for Saccharomyces cerevisiae and we analyze one pheromone response-related module in more detail, demonstrating the potential of ENIGMA to generate detailed predictions. CONCLUSION: It is increasingly recognized that perturbational expression compendia are essential to identify the gene networks underlying cellular function, and efforts to build these for different organisms are currently underway. We show that ENIGMA constitutes a valuable addition to the repertoire of methods to analyze such data.

Project description:BackgroundMany studies report about detection and functional characterization of cis-regulatory motifs in untranslated regions (UTRs) of mRNAs but little is known about the nature and functional role of their distribution. To address this issue we have developed a computational approach based on the use of data mining techniques. The idea is that of mining frequent combinations of translation regulatory motifs, since their significant co-occurrences could reveal functional relationships important for the post-transcriptional control of gene expression. The experimentation has been focused on targeted mitochondrial transcripts to elucidate the role of translational control in mitochondrial biogenesis and function.ResultsThe analysis is based on a two-stepped procedure using a sequential pattern mining algorithm. The first step searches for frequent patterns (FPs) of motifs without taking into account their spatial displacement. In the second step, frequent sequential patterns (FSPs) of spaced motifs are generated by taking into account the conservation of spacers between each ordered pair of co-occurring motifs. The algorithm makes no assumption on the relation among motifs and on the number of motifs involved in a pattern. Different FSPs can be found depending on different combinations of two parameters, i.e. the threshold of the minimum percentage of sequences supporting the pattern, and the granularity of spacer discretization. Results can be retrieved at the UTRminer web site: http://utrminer.ba.itb.cnr.it/. The discovered FPs of motifs amount to 216 in the overall dataset and to 140 in the human subset. For each FP, the system provides information on the discovered FSPs, if any. A variety of search options help users in browsing the web resource. The list of sequence IDs supporting each pattern can be used for the retrieval of information from the UTRminer database.ConclusionComputational prediction of structural properties of regulatory sequences is not trivial. The presented data mining approach is able to overcome some limits observed in other competitive tools. Preliminary results on UTR sequences from nuclear transcripts targeting mitochondria are promising and lead us to be confident on the effectiveness of the approach for future developments.

Dataset Information

Extracting regulatory modules from gene expression data by sequential pattern mining.

Publications

Extracting regulatory modules from gene expression data by sequential pattern mining.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets