13,701 research outputs found
Application of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data
We present two complementary approaches for the interpretation of clusters of
co-regulated genes, such as those obtained from DNA chips and related methods.
Starting from a cluster of genes with similar expression profiles, two basic
questions can be asked:
1. Which mechanism is responsible for the coordinated transcriptional response
of the genes? This question is approached by extracting motifs that are shared
between the upstream sequences of these genes. The motifs extracted are putative
cis-acting regulatory elements.
2. What is the physiological meaning for the cell to express together these
genes? One way to answer the question is to search for potential metabolic
pathways that could be catalyzed by the products of the genes. This can be
done by selecting the genes from the cluster that code for enzymes, and trying
to assemble the catalyzed reactions to form metabolic pathways.
We present tools to answer these two questions, and we illustrate their use with
selected examples in the yeast Saccharomyces cerevisiae. The tools are available
on the web (http://ucmb.ulb.ac.be/bioinformatics/rsa-tools/;
http://www.ebi.ac.uk/research/pfbp/; http://www.soi.city.ac.uk/~msch/)
Infinite factorization of multiple non-parametric views
Combined analysis of multiple data sources has increasing application interest, in particular for distinguishing shared and source-specific aspects. We extend this rationale of classical canonical correlation analysis into a flexible, generative and non-parametric clustering
setting, by introducing a novel non-parametric hierarchical
mixture model. The lower level of the model describes each source with a flexible non-parametric mixture, and the top level combines these to describe commonalities of the sources. The lower-level clusters arise from hierarchical Dirichlet Processes, inducing an infinite-dimensional contingency table between the views. The commonalities between the sources are modeled by an infinite block
model of the contingency table, interpretable as non-negative factorization of infinite matrices, or as a prior for infinite contingency tables. With Gaussian mixture components plugged in for continuous measurements, the model is applied to two views of genes, mRNA expression and abundance of the produced proteins, to expose groups of genes that are co-regulated in either or both of the views.
Cluster analysis of co-expression is a standard simple way of screening for co-regulation, and the two-view analysis extends the approach to distinguishing between pre- and post-translational regulation
Tree-guided group lasso for multi-response regression with structured sparsity, with an application to eQTL mapping
We consider the problem of estimating a sparse multi-response regression
function, with an application to expression quantitative trait locus (eQTL)
mapping, where the goal is to discover genetic variations that influence
gene-expression levels. In particular, we investigate a shrinkage technique
capable of capturing a given hierarchical structure over the responses, such as
a hierarchical clustering tree with leaf nodes for responses and internal nodes
for clusters of related responses at multiple granularity, and we seek to
leverage this structure to recover covariates relevant to each
hierarchically-defined cluster of responses. We propose a tree-guided group
lasso, or tree lasso, for estimating such structured sparsity under
multi-response regression by employing a novel penalty function constructed
from the tree. We describe a systematic weighting scheme for the overlapping
groups in the tree-penalty such that each regression coefficient is penalized
in a balanced manner despite the inhomogeneous multiplicity of group
memberships of the regression coefficients due to overlaps among groups. For
efficient optimization, we employ a smoothing proximal gradient method that was
originally developed for a general class of structured-sparsity-inducing
penalties. Using simulated and yeast data sets, we demonstrate that our method
shows a superior performance in terms of both prediction errors and recovery of
true sparsity patterns, compared to other methods for learning a
multivariate-response regression.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS549 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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
Trajectory-based differential expression analysis for single-cell sequencing data
Trajectory inference has radically enhanced single-cell RNA-seq research by enabling the study of dynamic changes in gene expression. Downstream of trajectory inference, it is vital to discover genes that are (i) associated with the lineages in the trajectory, or (ii) differentially expressed between lineages, to illuminate the underlying biological processes. Current data analysis procedures, however, either fail to exploit the continuous resolution provided by trajectory inference, or fail to pinpoint the exact types of differential expression. We introduce tradeSeq, a powerful generalized additive model framework based on the negative binomial distribution that allows flexible inference of both within-lineage and between-lineage differential expression. By incorporating observation-level weights, the model additionally allows to account for zero inflation. We evaluate the method on simulated datasets and on real datasets from droplet-based and full-length protocols, and show that it yields biological insights through a clear interpretation of the data. Downstream of trajectory inference for cell lineages based on scRNA-seq data, differential expression analysis yields insight into biological processes. Here, Van den Berge et al. develop tradeSeq, a framework for the inference of within and between-lineage differential expression, based on negative binomial generalized additive models
Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma
BACKGROUND: Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. RESULTS: A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. CONCLUSION: In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers
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