CLONE CLUSTERING BY HYBRIDIZATION

DNA sequencing by hybridization (SBH) Format 1 technique is based on e xperiments in which thousands of short oligomers are consecutively hyb ridized with dense arrays of clones. In this paper we present the desc ription of a method for obtaining hybridization signatures for individ ual clones that guarantees reproducibility despite a wide range of var iations in experimental circumstances, a sensitive method for signatur e comparison at prespecified significance levels, and a clustering alg orithm that correctly identifies clusters of significantly similar sig natures. The methods and the algorithm have been verified experimental ly on a control set of 422 signatures that originate from 9 distinct c lones of known sequence. Experiments indicate that only 30 to 50 oligo mer probes suffice for correct clustering. This information about the identity of clones can be used to guide both genomic and cDNA sequenci ng by SBH or by standard gel-based methods. (C) 1995 Academic Press, I nc.