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S A Rifkin

Publications and source records attributed to S A Rifkin.

3 recordsLinked to original sources

Geometry of gene expression dynamics.

MOTIVATION: A gene expression trajectory moves through a high dimensional space where each axis represents the mRNA abundance of a different gene. Genome wide gene expression has a dynamic structure, especially in studies of development and temporal response. Both visualization and analyses of such data require an explicit attention to the temporal structure. RESULTS: Using three cell cycle trajectories from Saccharomyces cerevisiae to illustrate, we present several techniques which reveal the geometry of the data. We import phase-delay time plots from chaotic systems theory as a dynamic data visualization device and show how these plots capture important aspects of the trajectories. We construct an objective function to find an optimal two-dimensional projection of the cell cycle, demonstrate that the system returns to this plane after three different initial perturbations, and explore the conditions under which this geometric approach outperforms standard approaches such as singular value decomposition and Fourier analysis. Finally, we show how a geometric analysis can isolate distinct parts of the trajectories, in this case the initial perturbation versus the cell cycle. CONTACT: junhyong.kim@yale.edu

Algorithms↗

Constraint structure analysis of gene expression.

A microarray experiment gives a snapshot of the state of an organism in terms of the relative abundances of its mRNA transcripts, locating the organism at a point in a high dimensional state space where each axis represents the relative expression level of a single gene. Multiple experiments generate a cloud of points in this gene expression space. We present a geometric approach to analyzing the covariational properties of such a cloud and use a dataset from Saccharomyces cerevisiae as an illustration. In particular, we use singular value decomposition to identify significant linear sub-structures in the data and analyze the contributions of both individual genes and functional classes of genes to these major directions of variation. Analyzing the publicly available yeast expression data, we show that under all experimental conditions the variation in expression is limited to a small number of linear dimensions. Projections of individual gene axes onto the significant dimensions can order the contribution of individual genes to variation in expression within an experiment. We show that no particular groups of genes characterize particular experimental conditions. Instead, the particular structure of the coordinated expression of the entire genome characterizes a particular experiment.

Gene Expression↗

Microarray analysis of Drosophila development during metamorphosis.

Metamorphosis is an integrated set of developmental processes controlled by a transcriptional hierarchy that coordinates the action of hundreds of genes. In order to identify and analyze the expression of these genes, high-density DNA microarrays containing several thousand Drosophila melanogaster gene sequences were constructed. Many differentially expressed genes can be assigned to developmental pathways known to be active during metamorphosis, whereas others can be assigned to pathways not previously associated with metamorphosis. Additionally, many genes of unknown function were identified that may be involved in the control and execution of metamorphosis. The utility of this genome-based approach is demonstrated for studying a set of complex biological processes in a multicellular organism.

Animals↗