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Sequencing-by-hybridization revisited: the analog-spectrum proposal

Content Provider	IEEE Xplore Digital Library
Author	Preparata, F.P.
Copyright Year	2004
Abstract	All published approaches to DNA sequencing by hybridization (SBH) consist of the biochemical acquisition of the spectrum of a target sequence (the set of its subsequences conforming to a given probing pattern) followed by the algorithmic reconstruction of the sequence from its spectrum. In the "standard" or "uniform" approach, the probing pattern is a string of length L and the length of reliably reconstructible sequences is known to be m/sub len/ = O(2/sup L/). For a fixed microarray area, higher sequencing performance can be achieved by inserting nonprobing gaps ("wild-cards") in the probing pattern. The reconstruction, however, must cope with the emergence of fooling probes due to the gaps and algorithmic failure occurs when the spectrum becomes too densely populated, although we can achieve m/sub comp/ = O(4/sup L/). Despite the combinatorial success of gapped probing, all current approaches are based on a biochemically unrealistic spectrum-acquisition model (digital-spectrum). The reality of hybridization is much more complex. Departing from the conventional model, in this paper, we propose an alternative, called the analog-spectrum model, which more closely reflects the biochemical process. This novel modeling reestablishes probe length as the performance-governing factor, adopting "semidegenerate bases" as suitable emulators of currently inadequate universal bases. One important conclusion is that accurate biochemical measurements are pivotal to the success of SBH. The theoretical proposal presented in this paper should be a convincing stimulus for the needed biotechnological work.
Sponsorship	IEEE Computer Society
Page Count	7
File Size	328529
Starting Page	46
Ending Page	52
File Format	PDF
ISSN	15455963
Volume Number	1
Issue Number	1
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2004-01-01
Publisher Place	U.S.A.
Access Restriction	One Nation One Subscription (ONOS)
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Proposals Sequences DNA Probes Libraries Thermodynamics Optical wavelength conversion Laboratories Labeling Visualization semidegenerate bases. Index Terms- DNA sequencing sequencing-by-hybridization microarrays gapped probes thermodynamics of hybridization analog spectrum
Content Type	Text
Resource Type	Article
Subject	Applied Mathematics Genetics Biotechnology

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