RICHARD KARP's Lecture, Fri., Feb. 3, 1995, 4:00 p.m.

Barbara Quigley bquigley at
Tue Jan 17 11:53:57 EST 1995

         		Distinguished Lecture Series

			       Richard Karp

		       Department of Computer Science

		     University of California, Berkeley

		         February 3, 1995, 4:00 p.m.

		   First Floor Lecture Hall, CoRE Building

			     Rutgers University

		        Reception will follow lecture

Algorithms for Physical Mapping of DNA Molecules

The goal of physical mapping is to identify the locations of landmarks along
a DNA molecule such as a chromosome. Physical mapping usually entails the 
construction of a clone library: a collection of overlapping fragments, or
clones, which cover the molecule several times. These clones are much too
large to be sequenced directly, but they can be partially characterized
experimentally. Given such a partial characterization, the problem is
to mathematically reassemble the ordering and arrangement of the clones and
of other associated landmarks.

The most common experimental techniques are multiple complete digestion and
STS mapping. In multiple complete digestion a clone is
digested with two or more restriction enzymes and the sizes of the restriction 
fragments are measured by gel electrophoresis. In STS mapping 
the polymerase chain reaction is used to test whether certain
DNA sequences called probes occur on the clone. Each of these probes is 
assumed to occur exactly once on the DNA molecule, and its site of
occurrence is called a Sequence tagged Site (STS)

We shall describe a battery of programs for STS mapping constructed by
Farid Alizadeh, Deborah Weisser, Geoffrey Zweig and the speaker. Given a 
matrix of incidences between probes and clones these programs seek to 
determine the order of the probes along the DNA. The problem is easily solved 
in the absence of measurement errors. In the presence of errors the problem
is more difficult, but we have attacked it successfully by combining local
search with preprocessing techniques for screening out some of the errors in
the data.

In closing, we shall describe some preliminary approaches to algorithms for
multiple-complete-digest mapping.

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