75,732 research outputs found
Under-approximating Cut Sets for Reachability in Large Scale Automata Networks
In the scope of discrete finite-state models of interacting components, we
present a novel algorithm for identifying sets of local states of components
whose activity is necessary for the reachability of a given local state. If all
the local states from such a set are disabled in the model, the concerned
reachability is impossible. Those sets are referred to as cut sets and are
computed from a particular abstract causality structure, so-called Graph of
Local Causality, inspired from previous work and generalised here to finite
automata networks. The extracted sets of local states form an
under-approximation of the complete minimal cut sets of the dynamics: there may
exist smaller or additional cut sets for the given reachability. Applied to
qualitative models of biological systems, such cut sets provide potential
therapeutic targets that are proven to prevent molecules of interest to become
active, up to the correctness of the model. Our new method makes tractable the
formal analysis of very large scale networks, as illustrated by the computation
of cut sets within a Boolean model of biological pathways interactions
gathering more than 9000 components
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
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