C C Whittaker | Search PubMed

PubMed1999

The stationary statistical properties of human coding sequences.

We introduce a generally applicable method for the discovery and quantitation of all of the characteristic statistical properties of a class of biological sequences, given examples from the class. This method employs a reversible binary encoding of sequences into the binary digits -1 and +1. Then, provided that the sample is sufficient, the sample cumulants on the subsets of digit positions will manifest all of the statistical properties of the class. As an illustration, we present the main results of a complete characterization of the stationary statistical properties of human coding sequences, in terms of their sample cumulants. Many of the telling sample cumulants are described.

Base Sequence↗

PubMed1995

Efficient pooling designs for library screening.

We describe efficient methods for screening clone libraries, based on pooling schemes that 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, and 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 resolved positive clones--clones that are definitely positive based upon the pool assays--as a criterion for the efficiency of a pooling design. We determine the value of k that 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 = 1298 clones. We also estimate the probability that each clone is positive, given the pool-assay data and a model for experimental errors.

Binomial Distribution↗