Browsing by Author "Smith, V Anne"

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Open Access
Advances to Bayesian network inference for generating causal networks from observational biological data.
(Bioinformatics, 2004-12-12) Yu, Jing; Smith, V Anne; Wang, Paul P; Hartemink, Alexander J; Jarvis, Erich D
MOTIVATION: Network inference algorithms are powerful computational tools for identifying putative causal interactions among variables from observational data. Bayesian network inference algorithms hold particular promise in that they can capture linear, non-linear, combinatorial, stochastic and other types of relationships among variables across multiple levels of biological organization. However, challenges remain when applying these algorithms to limited quantities of experimental data collected from biological systems. Here, we use a simulation approach to make advances in our dynamic Bayesian network (DBN) inference algorithm, especially in the context of limited quantities of biological data. RESULTS: We test a range of scoring metrics and search heuristics to find an effective algorithm configuration for evaluating our methodological advances. We also identify sampling intervals and levels of data discretization that allow the best recovery of the simulated networks. We develop a novel influence score for DBNs that attempts to estimate both the sign (activation or repression) and relative magnitude of interactions among variables. When faced with limited quantities of observational data, combining our influence score with moderate data interpolation reduces a significant portion of false positive interactions in the recovered networks. Together, our advances allow DBN inference algorithms to be more effective in recovering biological networks from experimentally collected data. AVAILABILITY: Source code and simulated data are available upon request. SUPPLEMENTARY INFORMATION: http://www.jarvislab.net/Bioinformatics/BNAdvances/
Open Access
Computational inference of neural information flow networks.
(PLoS Comput Biol, 2006-11-24) Smith, V Anne; Yu, Jing; Smulders, Tom V; Hartemink, Alexander J; Jarvis, Erich D
Determining how information flows along anatomical brain pathways is a fundamental requirement for understanding how animals perceive their environments, learn, and behave. Attempts to reveal such neural information flow have been made using linear computational methods, but neural interactions are known to be nonlinear. Here, we demonstrate that a dynamic Bayesian network (DBN) inference algorithm we originally developed to infer nonlinear transcriptional regulatory networks from gene expression data collected with microarrays is also successful at inferring nonlinear neural information flow networks from electrophysiology data collected with microelectrode arrays. The inferred networks we recover from the songbird auditory pathway are correctly restricted to a subset of known anatomical paths, are consistent with timing of the system, and reveal both the importance of reciprocal feedback in auditory processing and greater information flow to higher-order auditory areas when birds hear natural as opposed to synthetic sounds. A linear method applied to the same data incorrectly produces networks with information flow to non-neural tissue and over paths known not to exist. To our knowledge, this study represents the first biologically validated demonstration of an algorithm to successfully infer neural information flow networks.
Open Access
Evaluating functional network inference using simulations of complex biological systems.
(Bioinformatics, 2002) Smith, V Anne; Jarvis, Erich D; Hartemink, Alexander J
MOTIVATION: Although many network inference algorithms have been presented in the bioinformatics literature, no suitable approach has been formulated for evaluating their effectiveness at recovering models of complex biological systems from limited data. To overcome this limitation, we propose an approach to evaluate network inference algorithms according to their ability to recover a complex functional network from biologically reasonable simulated data. RESULTS: We designed a simulator to generate data representing a complex biological system at multiple levels of organization: behaviour, neural anatomy, brain electrophysiology, and gene expression of songbirds. About 90% of the simulated variables are unregulated by other variables in the system and are included simply as distracters. We sampled the simulated data at intervals as one would sample from a biological system in practice, and then used the sampled data to evaluate the effectiveness of an algorithm we developed for functional network inference. We found that our algorithm is highly effective at recovering the functional network structure of the simulated system-including the irrelevance of unregulated variables-from sampled data alone. To assess the reproducibility of these results, we tested our inference algorithm on 50 separately simulated sets of data and it consistently recovered almost perfectly the complex functional network structure underlying the simulated data. To our knowledge, this is the first approach for evaluating the effectiveness of functional network inference algorithms at recovering models from limited data. Our simulation approach also enables researchers a priori to design experiments and data-collection protocols that are amenable to functional network inference.
Open Access
Influence of network topology and data collection on network inference.
(Pac Symp Biocomput, 2003) Smith, V Anne; Jarvis, Erich D; Hartemink, Alexander J
We recently developed an approach for testing the accuracy of network inference algorithms by applying them to biologically realistic simulations with known network topology. Here, we seek to determine the degree to which the network topology and data sampling regime influence the ability of our Bayesian network inference algorithm, NETWORKINFERENCE, to recover gene regulatory networks. NETWORKINFERENCE performed well at recovering feedback loops and multiple targets of a regulator with small amounts of data, but required more data to recover multiple regulators of a gene. When collecting the same number of data samples at different intervals from the system, the best recovery was produced by sampling intervals long enough such that sampling covered propagation of regulation through the network but not so long such that intervals missed internal dynamics. These results further elucidate the possibilities and limitations of network inference based on biological data.