4,315 research outputs found
Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks
Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets.
Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses.
Availability: The methods outlined in this article have been implemented in Matlab and are available on request
Learning the structure of Bayesian Networks: A quantitative assessment of the effect of different algorithmic schemes
One of the most challenging tasks when adopting Bayesian Networks (BNs) is
the one of learning their structure from data. This task is complicated by the
huge search space of possible solutions, and by the fact that the problem is
NP-hard. Hence, full enumeration of all the possible solutions is not always
feasible and approximations are often required. However, to the best of our
knowledge, a quantitative analysis of the performance and characteristics of
the different heuristics to solve this problem has never been done before.
For this reason, in this work, we provide a detailed comparison of many
different state-of-the-arts methods for structural learning on simulated data
considering both BNs with discrete and continuous variables, and with different
rates of noise in the data. In particular, we investigate the performance of
different widespread scores and algorithmic approaches proposed for the
inference and the statistical pitfalls within them
An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems
The authors would like to thank the support on this research by the CRISP project (Combinatorial Responses In Stress Pathways) funded by the BBSRC (BB/F00513X/1) under the Systems Approaches to Biological Research (SABR) Initiative.Peer reviewedPublisher PD
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