2,630 research outputs found
Inference algorithms for gene networks: a statistical mechanics analysis
The inference of gene regulatory networks from high throughput gene
expression data is one of the major challenges in systems biology. This paper
aims at analysing and comparing two different algorithmic approaches. The first
approach uses pairwise correlations between regulated and regulating genes; the
second one uses message-passing techniques for inferring activating and
inhibiting regulatory interactions. The performance of these two algorithms can
be analysed theoretically on well-defined test sets, using tools from the
statistical physics of disordered systems like the replica method. We find that
the second algorithm outperforms the first one since it takes into account
collective effects of multiple regulators
Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles
Reconstructing transcriptional regulatory networks is an important task in
functional genomics. Data obtained from experiments that perturb genes by
knockouts or RNA interference contain useful information for addressing this
reconstruction problem. However, such data can be limited in size and/or are
expensive to acquire. On the other hand, observational data of the organism in
steady state (e.g. wild-type) are more readily available, but their
informational content is inadequate for the task at hand. We develop a
computational approach to appropriately utilize both data sources for
estimating a regulatory network. The proposed approach is based on a three-step
algorithm to estimate the underlying directed but cyclic network, that uses as
input both perturbation screens and steady state gene expression data. In the
first step, the algorithm determines causal orderings of the genes that are
consistent with the perturbation data, by combining an exhaustive search method
with a fast heuristic that in turn couples a Monte Carlo technique with a fast
search algorithm. In the second step, for each obtained causal ordering, a
regulatory network is estimated using a penalized likelihood based method,
while in the third step a consensus network is constructed from the highest
scored ones. Extensive computational experiments show that the algorithm
performs well in reconstructing the underlying network and clearly outperforms
competing approaches that rely only on a single data source. Further, it is
established that the algorithm produces a consistent estimate of the regulatory
network.Comment: 24 pages, 4 figures, 6 table
Gene-network inference by message passing
The inference of gene-regulatory processes from gene-expression data belongs
to the major challenges of computational systems biology. Here we address the
problem from a statistical-physics perspective and develop a message-passing
algorithm which is able to infer sparse, directed and combinatorial regulatory
mechanisms. Using the replica technique, the algorithmic performance can be
characterized analytically for artificially generated data. The algorithm is
applied to genome-wide expression data of baker's yeast under various
environmental conditions. We find clear cases of combinatorial control, and
enrichment in common functional annotations of regulated genes and their
regulators.Comment: Proc. of International Workshop on Statistical-Mechanical Informatics
2007, Kyot
Gene-network inference by message passing
The inference of gene-regulatory processes from gene-expression data belongs
to the major challenges of computational systems biology. Here we address the
problem from a statistical-physics perspective and develop a message-passing
algorithm which is able to infer sparse, directed and combinatorial regulatory
mechanisms. Using the replica technique, the algorithmic performance can be
characterized analytically for artificially generated data. The algorithm is
applied to genome-wide expression data of baker's yeast under various
environmental conditions. We find clear cases of combinatorial control, and
enrichment in common functional annotations of regulated genes and their
regulators.Comment: Proc. of International Workshop on Statistical-Mechanical Informatics
2007, Kyot
Gene-network inference by message passing
The inference of gene-regulatory processes from gene-expression data belongs
to the major challenges of computational systems biology. Here we address the
problem from a statistical-physics perspective and develop a message-passing
algorithm which is able to infer sparse, directed and combinatorial regulatory
mechanisms. Using the replica technique, the algorithmic performance can be
characterized analytically for artificially generated data. The algorithm is
applied to genome-wide expression data of baker's yeast under various
environmental conditions. We find clear cases of combinatorial control, and
enrichment in common functional annotations of regulated genes and their
regulators.Comment: Proc. of International Workshop on Statistical-Mechanical Informatics
2007, Kyot
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