Dataset Information

EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data.

ABSTRACT: RNA sequencing (RNA-Seq) measures genome-wide gene expression. RNA-Seq data is count-based rendering normal distribution models for analysis inappropriate. Normalization of RNA-Seq data to transform the data has limitations which can adversely impact the analysis. Furthermore, there are a few count-based methods for analysis of RNA-Seq data but they are essentially for pairwise analysis of treatment groups or multiclasses but not pattern-based to identify co-expressed genes.We adapted our extracting patterns and identifying genes methodology for RNA-Seq (EPIG-Seq) count data. The software uses count-based correlation to measure similarity between genes, quasi-Poisson modelling to estimate dispersion in the data and a location parameter to indicate magnitude of differential expression. EPIG-Seq is different than any other software currently available for pattern analysis of RNA-Seq data in that EPIG-Seq 1) uses count level data and supports cases of inflated zeros, 2) identifies statistically significant clusters of genes that are co-expressed across experimental conditions, 3) takes into account dispersion in the replicate data and 4) provides reliable results even with small sample sizes. EPIG-Seq operates in two steps: 1) extract the pattern profiles from data as seeds for clustering co-expressed genes and 2) cluster the genes to the pattern seeds and compute statistical significance of the pattern of co-expressed genes. EPIG-Seq provides a table of the genes with bootstrapped p-values and profile plots of the patterns of co-expressed genes. In addition, EPIG-Seq provides a heat map and principal component dimension reduction plot of the clustered genes as visual aids. We demonstrate the utility of EPIG-Seq through the analysis of toxicogenomics and cancer data sets to identify biologically relevant co-expressed genes. EPIG-Seq is available at: sourceforge.net/projects/epig-seq.EPIG-Seq is unlike any other software currently available for pattern analysis of RNA-Seq count level data across experimental groups. Using the EPIG-Seq software to analyze RNA-Seq count data across biological conditions permits the ability to extract biologically meaningful co-expressed genes associated with coordinated regulation.

SUBMITTER: Li J

PROVIDER: S-EPMC4804494 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data.

Li Jianying J Bushel Pierre R PR

BMC genomics 20160322

<h4>Background</h4>RNA sequencing (RNA-Seq) measures genome-wide gene expression. RNA-Seq data is count-based rendering normal distribution models for analysis inappropriate. Normalization of RNA-Seq data to transform the data has limitations which can adversely impact the analysis. Furthermore, there are a few count-based methods for analysis of RNA-Seq data but they are essentially for pairwise analysis of treatment groups or multiclasses but not pattern-based to identify co-expressed genes.<h ...[more]

PMID: 27004791

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Project description:A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions.Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and L1 starvation in C. elegans and after ultraviolet (UV) or ionizing radiation (IR)-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying biological processes affected by IR- and/or UV- induced DNA damage.EPIG competed with CLICK and performed better than CAST in extracting patterns from simulated data. EPIG extracted more biological informative patterns and co-expressed genes from both C. elegans and IR/UV-treated human fibroblasts. Using Gene Ontology analysis of the genes in the patterns extracted by EPIG, several key biological categories related to p53-dependent cell cycle control were revealed from the IR/UV data. Among them were mitotic cell cycle, DNA replication, DNA repair, cell cycle checkpoint, and G0-like status transition. EPIG can be applied to data sets from a variety of experimental designs.

Project description:BackgroundIdentifying differentially expressed genes between the same or different species is an urgent demand for biological and medical research. For RNA-seq data, systematic technical effects and different sequencing depths are usually encountered when conducting experiments. Normalization is regarded as an essential step in the discovery of biologically important changes in expression. The present methods usually involve normalization of the data with a scaling factor, followed by detection of significant genes. However, more than one scaling factor may exist because of the complexity of real data. Consequently, methods that normalize data by a single scaling factor may deliver suboptimal performance or may not even work.The development of modern machine learning techniques has provided a new perspective regarding discrimination between differentially expressed (DE) and non-DE genes. However, in reality, the non-DE genes comprise only a small set and may contain housekeeping genes (in same species) or conserved orthologous genes (in different species). Therefore, the process of detecting DE genes can be formulated as a one-class classification problem, where only non-DE genes are observed, while DE genes are completely absent from the training data.ResultsIn this study, we transform the problem to an outlier detection problem by treating DE genes as outliers, and we propose a scaling-free minimum enclosing ball (SFMEB) method to construct a smallest possible ball to contain the known non-DE genes in a feature space. The genes outside the minimum enclosing ball can then be naturally considered to be DE genes. Compared with the existing methods, the proposed SFMEB method does not require data normalization, which is particularly attractive when the RNA-seq data include more than one scaling factor. Furthermore, the SFMEB method could be easily extended to different species without normalization.ConclusionsSimulation studies demonstrate that the SFMEB method works well in a wide range of settings, especially when the data are heterogeneous or biological replicates. Analysis of the real data also supports the conclusion that the SFMEB method outperforms other existing competitors. The R package of the proposed method is available at https://bioconductor.org/packages/MEB .

Dataset Information

EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data.

Publications

EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data.

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