Restricting SBH Ambiguity via Restriction Enzymes

Skiena, Steven; Snir, Sagi

doi:10.1007/3-540-45784-4_30

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…Thus, if, for example, we wish to reconstruct at least 0.9 fraction of the sequences of length n, then n must be less than roughly 2 k [2,8,20,23]. Several methods for overcoming this limitation of SBH were proposed: interactive protocols [10,17,25,28], using location information [1,4,5,7,11,23], using a known homologous string [18,19,27], and using restriction enzymes [24,26].…”

Section: Introductionmentioning

confidence: 99%

Optimal Probing Patterns for Sequencing by Hybridization

Tsur

2006

Lecture Notes in Computer Science

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Sequencing by Hybridization (SBH) is a method for reconstructing a DNA sequence based on its k-mer content. This content, called the spectrum of the sequence, can be obtained from hybridization with a universal DNA chip. The main shortcoming of SBH is that it reliably reconstructs only sequences of length at most square root of the size of the chip. Frieze et al. [9] showed that by using gapped probes, SBH can reconstruct sequences with length that is linear in the size of the chip. In this work we investigate the optimal placement of the gaps in the probes, and give an algorithm for finding nearly optimal gap placement. Using our algorithm, we obtain a chip design which is more efficient than the chip of Frieze et al.

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Section: Introductionmentioning

confidence: 99%

Optimal Probing Patterns for Sequencing by Hybridization

Tsur

2006

Lecture Notes in Computer Science

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“…The objective here is to increase performance without increasing the cost (in our case, microarray size). Substantial progress in this direction has been recently made (Hannenhalli et al, 1996;Preparata et al, 1999;Preparata and Upfal, 2000;Frieze and Halldorsson, 2002;Skiena and Snir, 2002); among these performance-enhancing approaches, we restrict our attention to schemes using probing patterns which include unsampled gaps between sampled positions. A formal justification of the advantages provided by sampling gaps is given by Preparata et al (1999) and Preparata and Upfal (2000); suffice it to mention here that, since the length of the probing pattern governs the performance of sequencing, under the constraint of fixed microarray size (i.e., fixed probe library size), larger pattern length can be achieved by the adoption of gaps of unsampled positions.…”

Section: Introduction Nmentioning

confidence: 99%

DNA Sequencing by Hybridization Using Semi-Degenerate Bases

Preparata¹,

Oliver²

2004

J Comput Biol

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One way to enhance the performance of hybridization microarrrays for DNA de novo sequencing is the use of probing patterns with gaps of unsampled positions. Ideally, such gaps could be realized by the inclusion into microarray oligos (probes) of wild-card compounds, referred to as universal bases (which bind nonspecifically to natural bases). The suggested alternative is to deploy in the gap positions degenerate bases, i.e., uniform mixtures of the four natural bases, with ensuing deterioration of the hybridization signal. In this paper, we show that such signal loss is a minor shortcoming, compared with the fact that degenerate bases cannot be treated as universal. Indeed, the substantial spread of hybridization energies at any microarray feature is such that on overwhelming number of mismatches bind more strongly than legal matches. We observed, however, that much narrower energy spreads are exhibited by pairs of bases in the same strength class (A-T and C-G). We call semi-degenerate a gap position realized with bases in the same energy class and show that well-known sequence reconstruction algorithms can be modified to achieve substantial improvements in sequencing effectiveness. For example, with a 4 9 -feature microarray and an acceptable weakening of the hybridization signal, one may achieve lengths of about 4,000 bases (compared with < 250 of the standard uniform method). Our approach also incorporates the use of a spectrum expressed in terms of observed feature melting temperatures (analog spectrum), rather than binary decisions made directly at the biochemical level (digital spectrum). While universal bases represent the ultimate goal of sequencing by hybridization, semidegenerate natural bases are the most effective known substitute.

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“…As this number is large even for short strings, SBH is not considered competitive in comparison with standard gel-based sequencing technologies. Several methods for overcoming the limitations of SBH were proposed: alternative chip designs [7,10,15,21], using analog spectra [16], using location information [3-5, 9, 17], using a known homologous string [14], and using restriction enzymes [18].…”

Section: Introductionmentioning

confidence: 99%

Sequencing by Hybridization in Few Rounds

Tsur

2003

Algorithms - ESA 2003

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Sequencing by Hybridization (SBH) is a method for reconstructing an unknown DNA string based on obtaining, through hybridization experiments, whether certain short strings appear in the target string. Following Margaritis and Skiena [12], we study the SBH in rounds problem: The goal is to reconstruct an unknown string A (over a fixed alphabet) using queries of the form "does the string S appear in A?" for some query string S. The queries are performed in rounds, where the queries in each round depend on the answers to the queries in the previous rounds. We show that almost all strings of length n can be reconstructed in log * n rounds with O(n) queries per round.We also consider a variant of the problem in which for each substring query S, the answer is whether S appears once in the string A, appears at least twice in A, or does not appear in A. For this problem, we show that almost all strings can be reconstructed in 2 rounds of O(n) queries. Our results improve the previous results of Margaritis and Skiena [12] and Frieze and Halldórsson [8]. Moreover, the second result is optimal.

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Restricting SBH Ambiguity via Restriction Enzymes

Cited by 6 publications

References 17 publications

Optimal Probing Patterns for Sequencing by Hybridization

Optimal Probing Patterns for Sequencing by Hybridization

DNA Sequencing by Hybridization Using Semi-Degenerate Bases

Sequencing by Hybridization in Few Rounds

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