19,427 research outputs found
Application of new probabilistic graphical models in the genetic regulatory networks studies
This paper introduces two new probabilistic graphical models for
reconstruction of genetic regulatory networks using DNA microarray data. One is
an Independence Graph (IG) model with either a forward or a backward search
algorithm and the other one is a Gaussian Network (GN) model with a novel
greedy search method. The performances of both models were evaluated on four
MAPK pathways in yeast and three simulated data sets. Generally, an IG model
provides a sparse graph but a GN model produces a dense graph where more
information about gene-gene interactions is preserved. Additionally, we found
two key limitations in the prediction of genetic regulatory networks using DNA
microarray data, the first is the sufficiency of sample size and the second is
the complexity of network structures may not be captured without additional
data at the protein level. Those limitations are present in all prediction
methods which used only DNA microarray data.Comment: 38 pages, 3 figure
Network estimation in State Space Model with L1-regularization constraint
Biological networks have arisen as an attractive paradigm of genomic science
ever since the introduction of large scale genomic technologies which carried
the promise of elucidating the relationship in functional genomics. Microarray
technologies coupled with appropriate mathematical or statistical models have
made it possible to identify dynamic regulatory networks or to measure time
course of the expression level of many genes simultaneously. However one of the
few limitations fall on the high-dimensional nature of such data coupled with
the fact that these gene expression data are known to include some hidden
process. In that regards, we are concerned with deriving a method for inferring
a sparse dynamic network in a high dimensional data setting. We assume that the
observations are noisy measurements of gene expression in the form of mRNAs,
whose dynamics can be described by some unknown or hidden process. We build an
input-dependent linear state space model from these hidden states and
demonstrate how an incorporated regularization constraint in an
Expectation-Maximization (EM) algorithm can be used to reverse engineer
transcriptional networks from gene expression profiling data. This corresponds
to estimating the model interaction parameters. The proposed method is
illustrated on time-course microarray data obtained from a well established
T-cell data. At the optimum tuning parameters we found genes TRAF5, JUND, CDK4,
CASP4, CD69, and C3X1 to have higher number of inwards directed connections and
FYB, CCNA2, AKT1 and CASP8 to be genes with higher number of outwards directed
connections. We recommend these genes to be object for further investigation.
Caspase 4 is also found to activate the expression of JunD which in turn
represses the cell cycle regulator CDC2.Comment: arXiv admin note: substantial text overlap with arXiv:1308.359
Modeling dependent gene expression
In this paper we propose a Bayesian approach for inference about dependence
of high throughput gene expression. Our goals are to use prior knowledge about
pathways to anchor inference about dependence among genes; to account for this
dependence while making inferences about differences in mean expression across
phenotypes; and to explore differences in the dependence itself across
phenotypes. Useful features of the proposed approach are a model-based
parsimonious representation of expression as an ordinal outcome, a novel and
flexible representation of prior information on the nature of dependencies, and
the use of a coherent probability model over both the structure and strength of
the dependencies of interest. We evaluate our approach through simulations and
in the analysis of data on expression of genes in the Complement and
Coagulation Cascade pathway in ovarian cancer.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS525 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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