9,849 research outputs found
Inferring gene expression dynamics via functional regression analysis
<p>Abstract</p> <p>Background</p> <p>Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other.</p> <p>Results</p> <p>We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for <it>Drosophila</it>, using temporal gene expression profiles.</p> <p>Conclusion</p> <p>Our findings point to specific reactivation patterns of gene expression during the <it>Drosophila </it>life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.</p
Reconstructing dynamical networks via feature ranking
Empirical data on real complex systems are becoming increasingly available.
Parallel to this is the need for new methods of reconstructing (inferring) the
topology of networks from time-resolved observations of their node-dynamics.
The methods based on physical insights often rely on strong assumptions about
the properties and dynamics of the scrutinized network. Here, we use the
insights from machine learning to design a new method of network reconstruction
that essentially makes no such assumptions. Specifically, we interpret the
available trajectories (data) as features, and use two independent feature
ranking approaches -- Random forest and RReliefF -- to rank the importance of
each node for predicting the value of each other node, which yields the
reconstructed adjacency matrix. We show that our method is fairly robust to
coupling strength, system size, trajectory length and noise. We also find that
the reconstruction quality strongly depends on the dynamical regime
How to understand the cell by breaking it: network analysis of gene perturbation screens
Modern high-throughput gene perturbation screens are key technologies at the
forefront of genetic research. Combined with rich phenotypic descriptors they
enable researchers to observe detailed cellular reactions to experimental
perturbations on a genome-wide scale. This review surveys the current
state-of-the-art in analyzing perturbation screens from a network point of
view. We describe approaches to make the step from the parts list to the wiring
diagram by using phenotypes for network inference and integrating them with
complementary data sources. The first part of the review describes methods to
analyze one- or low-dimensional phenotypes like viability or reporter activity;
the second part concentrates on high-dimensional phenotypes showing global
changes in cell morphology, transcriptome or proteome.Comment: Review based on ISMB 2009 tutorial; after two rounds of revisio
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
A machine learning pipeline for discriminant pathways identification
Motivation: Identifying the molecular pathways more prone to disruption
during a pathological process is a key task in network medicine and, more in
general, in systems biology.
Results: In this work we propose a pipeline that couples a machine learning
solution for molecular profiling with a recent network comparison method. The
pipeline can identify changes occurring between specific sub-modules of
networks built in a case-control biomarker study, discriminating key groups of
genes whose interactions are modified by an underlying condition. The proposal
is independent from the classification algorithm used. Three applications on
genomewide data are presented regarding children susceptibility to air
pollution and two neurodegenerative diseases: Parkinson's and Alzheimer's.
Availability: Details about the software used for the experiments discussed
in this paper are provided in the Appendix
Efficient inference of parsimonious phenomenological models of cellular dynamics using S-systems and alternating regression
The nonlinearity of dynamics in systems biology makes it hard to infer them
from experimental data. Simple linear models are computationally efficient, but
cannot incorporate these important nonlinearities. An adaptive method based on
the S-system formalism, which is a sensible representation of nonlinear
mass-action kinetics typically found in cellular dynamics, maintains the
efficiency of linear regression. We combine this approach with adaptive model
selection to obtain efficient and parsimonious representations of cellular
dynamics. The approach is tested by inferring the dynamics of yeast glycolysis
from simulated data. With little computing time, it produces dynamical models
with high predictive power and with structural complexity adapted to the
difficulty of the inference problem.Comment: 14 pages, 2 figure
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