George Mason University
CSI/Statistics Colloquium Series
Seminar Announcement
A Gene Expression Database for Cancer Drug Discovery:
Omics and Informatics
John N. Weinstein
Laboratory of Molecular Pharmacology
National Cancer Institute
ABSTRACT
The current revolution in drug discovery is based largely on
developments
in molecular biology and informatics. A case in point is the drug
discovery program of the National Cancer Institute, which has profiled
more than 65,000 compounds for their activity against 60 human cancer cell
lines.
The resulting patterns of activity (pharmacological fingerprints) have
proved rich in information on mechanisms of drug action and resistance
(Paull, et al., JNCI 81:1088,1989; Weinstein, et al., Science
258:447,
1992). To characterize the 60 cell types (and selected transfectants)
with
respect to molecular markers, we have done careful parallel harvests
of
DNA, RNA, and protein for what I have termed "omic" studies
(Weinstein,
Science 282:5389, 1998) -- including protein expression profiling and RNA
expression profiling by high density cDNA and oligonucleotide
microarrays.
The data complement those of the NCI's Cancer Genome Anatomy Project
in
that the 60 cell line "patients," unlike most human ones, have
extensive,
well-defined treatment histories -- i.e., they have been treated with
>65,000 agents one at a time and independently. The drug and gene
databases challenge our capabilities for data mining -- especially
when we
are forced to integrate the bioinformatics with the chemoinformatics
(Weinstein, et al., Science 275:343, 1997). In this seminar, I will
try to
communicate the nature of that challenge and how we have addressed it.
(Many others have contributed to this work, including U Scherf, M
Waltham,
TG Myers, WC Reinhold, L Smith, L Tanabe, JK Lee, D Andrews, J
Buolamwini,
W van Osdol, G Li, DA Scudiero, NL Anderson, DT Ross, M Eisen, PO
Brown, D
Botstein, D Shalon, E Lashkari, R Simon, L McShane, E Lander, T Golub,
H
Coller, P Tamayo, D Slonum, KW Kohn, Y Pommier, EA Sausville, and KD Paull.)
Friday, December 4, 1998
George W. Johnson Center, Assembly Room E
Refreshments at 10:30 a.m.
Seminar at 10:45 a.m.