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Transcript
The University of Chicago
Department of Statistics
Ph.D. Seminar
OMAR DE LA CRUZ
Department of Statistics
The University of Chicago
Geometric Approaches in the Analysis of Genetic Data
WEDNESDAY, July 30, 2008 at 3:00 PM
110 Eckhart Hall, 5734 S. University Avenue
ABSTRACT
We propose a method for detecting cell-cycle-regulated genes by studying the geometric
structure of gene expression data obtained by assaying individual cells from a growing population: under reasonable assumptions, the data points will cluster around a closed curve
that represents the ideal evolution of gene expression during the cell cycle. We describe a
statistical model as well as a general strategy for fitting the data, divided in two main steps:
first, using robust local orthogonal regression to obtain an initial estimate of the curve; and
second, improving the likelihood of the estimate by direct search.
The method sketched above leads in a natural way to the notion of geometric learning.
We will present some theoretical contributions to this field, by showing that the robust local
orthogonal regression approach corresponds, when the sample size goes to infinity, to the
detection of what we call modal ridges in the density of the distribution induced by the
model. However, these theoretical results are not directly applicable to the case of cycleregulated gene expression, since they depend on large sample sizes.
We also discuss how to integrate geometric learning with more traditional statistical
procedures, like regression, as a way to obtain more easily interpretable inferences. This
makes it possible to establish which coordinates contribute significantly to the geometric
structure (e.g., which genes are cycle-regulated). Also, it makes it possible to adjust for the
influence of the geometric structure, in order to more accurately measure other properties
of the individuals; for example, in studies of gene expression in single cells, adjusting for the
cell cycle allows a more accurate estimation of other characteristics, like membership in cell
subpopulations or treatment effects.
Information about building access for persons with disabilities may be obtained in advance by calling Jewanna Carver
at 773.834-5169 or by email ([email protected]).