On the power of universal bases in sequencing by hybridization
RECOMB '99 Proceedings of the third annual international conference on Computational molecular biology
MFCS '94 Proceedings of the 19th International Symposium on Mathematical Foundations of Computer Science 1994
The method of N-grams in large-scale clustering of DNA texts
Pattern Recognition
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DNA sequencing by hybridization, proposed about a decade ago as an alternative to standard electrophoresis-based sequencing techniques, is relevant not only to sequencing per se but also to diagnostics and therapeutics. The inherent structural inadequacy of traditional probe patterns and well-known hybridization shortcomings had for some time deflated the interest in this approach. Renewed interest for this topic has been generated by our recent discovery of a novel probing scheme whose performance for the first time asymptotically meets the information theory bound. After settling the question of asymptotic performance, due to the sizable volume of potential applications, the research focus has naturally shifted to issues of algorithmic fine tunings aimed at improving the performance "constants". In this paper, we introduce as a figure of merit the nucleotide-per-feature ratio (for a given confidence level), i.e., the length of a reliabily reconstructible (random) sequence divided by the number of probes placed on the sequencing array, regardless of the fabrication technology, and we explore the capabilities offered by the joint use of multiple different arrays in sequencing the same DNA sequence. In particular we consider a probing scheme based on the use of the spectra pertaining to a given probing pattern and to its reversal (referred to here as tandem spectra), and we show analytically and experimentally a performance improvement per unit of microarray area of about 4/3 (in a representative instance) over the conventional single-spectrum approach. The proposed tandem-spectrum reconstruction, in conjunction with a "voting provision" discussed elsewhere (whereby one of two competing alternatives is chosen if the corresponding probes are less numerous in the current prefix of the reconstructive sequence), is the best known technique for sequencing by hybridization.