Nucleic Acids Research, 2003, Vol. 31, No. 19 5667-5675
© 2003 Oxford University Press
Advanced computational techniques for re-sequencing DNA with polymerase signaling assay arrays
1 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel, 2 School of Computer Science, Tel Aviv University, Tel Aviv, Israel and 3 Orchid Biosciences Inc., Princeton, NJ, USA
*To whom correspondence should be addressed. Tel: +972 8 9344907; Fax: +972 8 9344487; Email: peer{at}wicc.weizmann.ac.il
Re-sequencing, the identification of the specific variants in a sequence of interest compared with a known genomic sequence, is a ubiquitous task in today’s biology. Universal arrays, which interrogate all possible oligonucleotides of a certain length in a target sequence, have been suggested for computationally determining a polynucleotide sequence from its oligonucleotide content. We present here new methods that use such arrays for re-sequencing. Our methods are applied to data obtained by the polymerase signaling assay, which arrays single-based primer extension reactions for either universal or partial arrays of pentanucleotides. The computational analysis uses the spectrum alignment algorithm, which is refined and enhanced here in order to overcome noise incurred by the use of such short primers. We present accurate re-sequencing results for both synthetic and amplified DNA molecules.