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Evaluating functional network inference using simulations of complex biological systems.

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Date
2002
Authors
Smith, V Anne
Jarvis, Erich D
Hartemink, Alexander J
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Abstract
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.
Type
Journal article
Subject
Adaptation, Physiological
Algorithms
Animals
Brain
Computer Simulation
Gene Expression Profiling
Gene Expression Regulation
Models, Neurological
Signal Transduction
Songbirds
Vocalization, Animal
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https://hdl.handle.net/10161/11225
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Scholars@Duke

Hartemink

Alexander J. Hartemink

Professor of Computer Science
Computational biology, machine learning, Bayesian statistics, transcriptional regulation, genomics and epigenomics, graphical models, Bayesian networks, hidden Markov models, systems biology, computational neurobiology, classification, feature selection
Jarvis

Erich David Jarvis

Adjunct Professor in the Deptartment of Neurobiology
Dr. Jarvis' laboratory studies the neurobiology of vocal communication. Emphasis is placed on the molecular pathways involved in the perception and production of learned vocalizations. They use an integrative approach that combines behavioral, anatomical, electrophysiological and molecular biological techniques. The main animal model used is songbirds, one of the few vertebrate groups that evolved the ability to learn vocalizations. The generality of the discoveries is tested in other vocal lear
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