Efficient pooling designs for library screening

arXivmath/9412222MaRDI QIDQ6503576FDOQ6503576

Authors: William J. Bruno, Emanuel Knill, David Joseph Balding, D. C. Bruce, N. A. Doggett, W. W. Sawhill, R. L. Stallings, Craig C. Whittaker, David C. Torney 

Abstract: We describe efficient methods for screening clone libraries, based on pooling schemes which we call ``random $k$-sets designs. In these designs, the pools in which any clone occurs are equally likely to be any possible selection of $k$ from the $v$ pools. The values of $k$ and $v$ can be chosen to optimize desirable properties. Random $k$-sets designs have substantial advantages over alternative pooling schemes: they are efficient, flexible, easy to specify, require fewer pools, and have error-correcting and error-detecting capabilities. In addition, screening can often be achieved in only one pass, thus facilitating automation. For design comparison, we assume a binomial distribution for the number of ``positive clones, with parameters $n$, the number of clones, and $c$, the coverage. We propose the expected number of {em resolved positive} clones---clones which are definitely positive based upon the pool assays---as a criterion for the efficiency of a pooling design. We determine the value of $k$ which is optimal, with respect to this criterion, as a function of $v$, $n$ and $c$. We also describe superior $k$-sets designs called $k$-sets packing designs. As an illustration, we discuss a robotically implemented design for a 2.5-fold-coverage, human chromosome 16 YAC library of $n=1,298$ clones. We also estimate the probability each clone is positive, given the pool-assay data and a model for experimental errors.

Mathematics Subject Classification ID

General biology and biomathematics (92B05)

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