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General Departmental Seminar Series

Algorithms For Detecting Gene Copy Number Fluctuations in Tumor Cells by Microarrays"

Bud Mishra, Courant Institute, New York University

Monday, Feb 19, 2001, 1:30 pm

Auditorium, Genetics/Biotechnology Center, 425 Henry Mall


Hybridization, a process by which two complementary DNA strands match by sequence specific base-pairing and form a double-stranded DNA complex, has become a fundamental tool of genomics as it permits the usage of DNA molecules themselves as the perfect reagent to identify particular DNA sequences. Recently, microarrays have allowed many such hybridization experiments to proceed concurrently, thus promising high throughput.

A key biological problem in this context can be abstracted to a graph-theoretic problem concerned with embedding its vertices on a real line in such a manner that the pair-wise distance measurements among the vertices are "preserved." We study a wide class of distributions for the distance measurements and suggest several algorithms to solve it with good accuracy and efficiency, i.e., O(E log V + V^2). We give a probabilistic analysis of the case when the distance metric is inferred from a set of microarray experiments using short probes hybridized to pooled fluorochrome labeled clones from a large library.

We shall also explore various limitations of this technology due to several error sources (noisy signal detection, imperfect base-pairing, non-specific cross-hybridization, etc.) and suggest ways to overcome them via algorithmic and statistical means. In particular, we shall focus on two specific applications1) Rapid detection of gene amplifications (involving oncogenes) and gene deletion (involving tumor suppressor genes) in cancerous tumor cells, 2) Rapid and accurate placement of low-complexity probes along the genome to characterize gene amplification and deletions.

(Jointly with CSHL's Wigler-Lab and MSKCC's Norton-Lab)

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