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Nicholas Geard

Publications and source records attributed to Nicholas Geard.

2 recordsLinked to original sources

A gene network model for developing cell lineages.

Biological development is a remarkably complex process. A single cell, in an appropriate environment, contains sufficient information to generate a variety of differentiated cell types, whose spatial and temporal dynamics interact to form detailed morphological patterns. While several different physical and chemical processes play an important role in the development of an organism, the locus of control is the cell's gene regulatory network. We designed a dynamic recurrent gene network (DRGN) model and evaluated its ability to control the developmental trajectories of cells during embryogenesis. Three tasks were developed to evaluate the model, inspired by cell lineage specification in C. elegans, describing the variation in gene activity required for early cell diversification, combinatorial control of cell lineages, and cell lineage termination. Three corresponding sets of simulations compared performance on the tasks for different gene network sizes, demonstrating the ability of DRGNs to perform the tasks with minimal external input. The model and task definition represent a new means of linking the fundamental properties of genetic networks with the topology of the cell lineages whose development they control.

Animals↗

Towards more biological mutation operators in gene regulation studies.

Genetic regulation is often viewed as a complex system whose properties emerge from the interaction of regulatory genes. One major paradigm for studying the complex dynamics of gene regulation uses directed graphs to explore structure, behaviour and evolvability. Mutation operators used in such studies typically involve the insertion and deletion of nodes, and the insertion, deletion and rewiring of links at the network level. These network-level mutational operators are sufficient to allow the statistical analysis of network structure, but impose limitations on the way networks are evolved. There are a wide variety of mutations in DNA sequences that have yet to be analysed for their network-level effects. By modelling an artificial genome at the level of nucleotide sequences and mapping it to a regulatory network, biologically grounded mutation operators can be mapped to network-level mutations. This paper analyses five such sequence level mutations (single-point mutation, transposition, inversion, deletion and gene duplication) for their effects at the network level. Using analytic and simulation techniques, we show that it is rarely the case that nodes and links are cleanly added or deleted, with even the simplest point mutation causing a wide variety of network-level modifications. As expected, the vast majority of simple (single-point) mutations are neutral, resulting in a neutral plateau from which a range of functional behaviours can be reached. By analysing the effects of sequence-level mutations at the network level of gene regulation, we aim to stimulate more careful consideration of mutation operators in gene regulation models than has previously been given.

Algorithms↗