1,919 research outputs found
A Posterior Probability Approach for Gene Regulatory Network Inference in Genetic Perturbation Data
Inferring gene regulatory networks is an important problem in systems
biology. However, these networks can be hard to infer from experimental data
because of the inherent variability in biological data as well as the large
number of genes involved. We propose a fast, simple method for inferring
regulatory relationships between genes from knockdown experiments in the NIH
LINCS dataset by calculating posterior probabilities, incorporating prior
information. We show that the method is able to find previously identified
edges from TRANSFAC and JASPAR and discuss the merits and limitations of this
approach
Augmented Sparse Reconstruction of Protein Signaling Networks
The problem of reconstructing and identifying intracellular protein signaling
and biochemical networks is of critical importance in biology today. We sought
to develop a mathematical approach to this problem using, as a test case, one
of the most well-studied and clinically important signaling networks in biology
today, the epidermal growth factor receptor (EGFR) driven signaling cascade.
More specifically, we suggest a method, augmented sparse reconstruction, for
the identification of links among nodes of ordinary differential equation (ODE)
networks from a small set of trajectories with different initial conditions.
Our method builds a system of representation by using a collection of integrals
of all given trajectories and by attenuating block of terms in the
representation itself. The system of representation is then augmented with
random vectors, and minimization of the 1-norm is used to find sparse
representations for the dynamical interactions of each node. Augmentation by
random vectors is crucial, since sparsity alone is not able to handle the large
error-in-variables in the representation. Augmented sparse reconstruction
allows to consider potentially very large spaces of models and it is able to
detect with high accuracy the few relevant links among nodes, even when
moderate noise is added to the measured trajectories. After showing the
performance of our method on a model of the EGFR protein network, we sketch
briefly the potential future therapeutic applications of this approach.Comment: 24 pages, 6 figure
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
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