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BCIT Citations Collection

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Using evolutionary computations to understand the design and evolution of gene and cell regulatory networks
This paper surveys modeling approaches for studying the evolution of gene regulatory networks (GRNs). Modeling of the design or ‘wiring’ of GRNs has become increasingly common in developmental and medical biology, as a means of quantifying gene–gene interactions, the response to perturbations, and the overall dynamic motifs of networks. Drawing from developments in GRN ‘design’ modeling, a number of groups are now using simulations to study how GRNs evolve, both for comparative genomics and to uncover general principles of evolutionary processes. Such work can generally be termed evolution in silico. Complementary to these biologically-focused approaches, a now well-established field of computer science is Evolutionary Computations (ECs), in which highly efficient optimization techniques are inspired from evolutionary principles. In surveying biological simulation approaches, we discuss the considerations that must be taken with respect to: (a) the precision and completeness of the data (e.g. are the simulations for very close matches to anatomical data, or are they for more general exploration of evolutionary principles); (b) the level of detail to model (we proceed from ‘coarse-grained’ evolution of simple gene-gene interactions to ‘fine-grained’ evolution at the DNA sequence level); (c) to what degree is it important to include the genome’s cellular context; and (d) the efficiency of computation. With respect to the latter, we argue that developments in computer science EC offer the means to perform more complete simulation searches, and will lead to more comprehensive biological predictions., Peer-reviewed article, Published.
Variable patterning in fruit fly embryos due to basins of attraction in underlying gene regulatory dynamics
Proceedings of Previous work on a reaction-diffusion model of a 4-gene regulatory network governing insect segmentation characterized the dynamical basis of robustness to perturbations in this system [1,2]. Here, we computationally study system behavior near bifurcation points corresponding to weak-allele mutant embryos (i.e. with altered gene regulation). Our computations suggest that the variable expressivity and incomplete penetrance observed in some gene mutations may stem from response of the dynamical system to variable input (regulatory genes) near such bifurcation points., Peer-reviewed article, Published. Received: 14 April 2012; Accepted: 2 October 2012.
Variation of select flavonols and chlorogenic acid content of elderberry collected throughout the Eastern United States
American elderberries are commonly collected from wild plants for use as food and medicinal products. The degree of phytochemical variation among wild populations has not been established and might affect the overall quality of elderberry dietary supplements. The three major flavonols identified in elderberries are rutin, quercetin and isoquercetin. Variation in the flavonols and chlorogenic acid was determined for 107 collections of elderberries from throughout the eastern United States using an optimized high performance liquid chromatography with ultraviolet detection method. The mean content was 71.9 mg per 100 g fresh weight with variation ranging from 7.0 to 209.7 mg per 100 g fresh weight within the collected population. Elderberries collected from southeastern regions had significantly higher contents in comparison with those in more northern regions. The variability of the individual flavonol and chlorogenic acid profiles of the berries was complex and likely influenced by multiple factors. Several outliers were identified based on unique phytochemical profiles in comparison with average populations. This is the first study to determine the inherent variability of American elderberries from wild collections and can be used to identify potential new cultivars that may produce fruits of unique or high-quality phytochemical content for the food and dietary supplement industries., Peer-reviewed article, Published. Received 16 April 2015; Revised 29 October 2015; Accepted 20 December 2015; Available online 23 December 2015.

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