Nucleic Acids Research, Vol 26, Issue 4 879-886, Copyright © 1998 by Oxford University Press
B Ward and T Juehne
A method is described for measuring the diversity of combinatorial
oligonucleotide libraries that entails extrapolating the base composition
of a co-synthesized model library (dNC, N = A, C, G, T) to that of a
multibase library template. The base composition of dNC was measured by
HPLC. The ability of dNC to predict the base composition of a multibase
library template was corroborated by measuring the composition of a 12 base
combinatorial library. The base composition of the 12 base library was
determined by several template dependent incorporation assays: measurement
of restriction fragment specific activities from polymerase
incorporation/restriction enzyme digests, template directed radionucleotide
primer extension and quantitative dideoxynucleotide sequencing.
Additionally, a convention for describing oligomeric combinatorial library
(OCL) diversity is proposed. The convention uses a quantity termed the
diversity quotient (Qd) to describe library breadth and the mole fraction
of the least represented monomeric unit of the OCL to calculate minimum
library quantity requirements. Similar methods/conventions could presumably
be developed/adopted for non-nucleic acid libraries.
ARTICLES
Combinatorial library diversity: probability assessment of library populations
Sigma Chemical Company, PO Box 14508, St Louis, MO 63178, USA. bwardhome@rocketmail.com
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