The Experts below are selected from a list of 25710 Experts worldwide ranked by ideXlab platform
A D Mirzabekov - One of the best experts on this subject based on the ideXlab platform.
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Sequencing by Hybridization with the generic 6 mer oligonucleotide microarray an advanced scheme for data processing
Journal of Biomolecular Structure & Dynamics, 2000Co-Authors: V R Chechetkin, Dmitri Proudnikov, A Y Turygin, Dmitry Prokopenko, Eu V Kirillov, A D MirzabekovAbstract:Abstract DNA Sequencing by Hybridization was carried out with a microarray of all 46 = 4,096 hexadeoxyribonucleotides (the generic microchip). The oligonucleotides immobilized in 100 × 100 × 20µm polyacrylamide gel pads of the generic microchip were hybridized with fluorescently labeled ssDNA, providing perfect and mismatched duplexes. Melting curves were measured in parallel for all microchip duplexes with a fluorescence microscope equipped with CCD camera. This allowed us to discriminate the perfect duplexes formed by the oligonucleotides, which are complementary to the target DNA. The DNA sequence was reconstructed by overlapping the complementary oligonucleotide probes. We developed a data processing scheme to heighten the discrimination of perfect duplexes from mismatched ones. The procedure was united with a reconstruction of the DNA sequence. The scheme includes the proper definition of a discriminant signal, preprocessing, and the variational principle for the sequence indicator function. The effe...
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parallel thermodynamic analysis of duplexes on oligodeoxyribonucleotide microchips
Nucleic Acids Research, 1998Co-Authors: Alexander Fotin, A D Mirzabekov, Aleksei Drobyshev, Dmitri Proudnikov, Alexander N PerovAbstract:A microchip method has been developed for massive and parallel thermodynamic analyses of DNA duplexes. Fluorescently labeled oligonucleotides were hybridized with oligonucleotides immobilized in the 100 x 100 x 20 mum gel pads of the microchips. The equilibrium melting curves for all microchip duplexes were measured in real time in parallel for all microchip duplexes. Thermodynamic data for perfect and mismatched duplexes that were obtained using the microchip method directly correlated with data obtained in solution. Fluorescent labels or longer linkers between the gel and the oligonucleotides appeared to have no significant effect on duplex stability. Extending the immobilized oligonucleotides with a four-base mixture from the 3'-end or one or two universal bases (5-nitroindole) from the 3'- and/or 5'-end increased the stabilities of their duplexes. These extensions were applied to increase the stabilities of the duplexes formed with short oligonucleotides in microchips, to significantly lessen the differences in melting curves of the AT- and GC-rich duplexes, and to improve discrimination of perfect duplexes from those containing poorly recognized terminal mismatches. This study explored a way to increase the efficiency of Sequencing by Hybridization on oligonucleotide microchips.
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dna Sequencing by Hybridization to microchip octa and decanucleotides extended by stacked pentanucleotides
Nucleic Acids Research, 1996Co-Authors: Sergei Parinov, A D Mirzabekov, Gennady Yershov, Victor Barsky, Alexander Belgovskiy, Eugene Kirillov, Edward N TimofeevAbstract:The efficiency of Sequencing by Hybridization to an oligonucleotide microchip grows with an increase in the number and in the length of the oligonucleotides; however, such increases raise enormously the complexity of the microchip and decrease the accuracy of Hybridization. We have been developing the technique of contiguous stacking Hybridization (CSH) to circumvent these shortcomings. Stacking interactions between adjacent bases of two oligonucleotides stabilize their contiguous duplex with DNA. The use of such stacking increases the effective length of microchip oligonucleotides, enhances Sequencing accuracy and allows the Sequencing of longer DNA. The effects of mismatches, base composition, length and other factors on the stacking are evaluated. Contiguous stacking Hybridization of DNA with immobilized 8mers and one or two 5mers labeled with two different fluorescent dyes increases the effective length of Sequencing oligonucleotides from 8 to 13 and 18 bases, respectively. The incorporation of all four bases or 5-nitroindole as a universal base into different positions of the 5mers permitted a decrease in the number of additional rounds of Hybridization. Contiguous stacking Hybridization appears to be a promising approach to significantly increasing the efficiency of Sequencing by Hybridization.
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dna Sequencing by Hybridization with oligonucleotides immobilized in a gel chemical ligation as a method of expanding the prospects for the method
Molecular Biology, 1994Co-Authors: S A Kuznetsova, A D Mirzabekov, I E Kanevskiĭ, V A Florentev, Z A ShabarovaAbstract:Chemical ligation was used to obtain a series of modified DNA duplexes containing a substituted pyrophosphate internucleotide bound in a given site of the sugar-phosphate backbone. The efficiency of chemical ligation was shown to depend on the structure of the synthesis center for the modified internucleotide bond, thermosiability of the initial DNA complexes, as well as the nature of the non-nucleotide substituent. Maximal yields (up to 77%) were obtained with DNA complexes of regular structure using for condensation the H-butylamide oligonucleotide derivatives on the terminal phosphate group. Conditions were selected for rapid quantitative cleavage of the substituted pyrophosphate bond in aqueous medium (pH 8.0). It was established that modified oligonucleotides which have a phosphoester bond between the phosphate group and the non-nucleotide substituent are more labile than the corresponding compounds with a phosphoamide bond. The results obtained may be useful for DNA Sequencing by Hybridization with a set of oligonucleotides. This will allow one to achieve unambiguous recognition of nucleotide sequences containing DNA with repeats and thus extend considerably the sphere of application of the method.
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dna Sequencing by Hybridization to oligonucleotide matrix calculation of continuous stacking Hybridization efficiency
Journal of Biomolecular Structure & Dynamics, 1994Co-Authors: Lysov Yup, A A Chernyi, Alexander Balaeff, K L Beattie, A D MirzabekovAbstract:In this paper we consider the efficiency of additional rounds of "continuous stacking" Hybridization in DNA sequence reconstruction by Hybridization with oligonucleotide matrix (SHOM). After the initial Hybridization of target DNA with the matrix of oligonucleotides of fixed length L some additional Hybridizations should be carried out in the presence of fluorescently labeled oligonucleotides of another length l. These additional oligonucleotides can hybridize in tandem with matrix tuples (continuous stacking Hybridization) thus forming an extended duplex with the target DNA strand. The additional data obtained allows resolutions of branching points arising in the reconstruction procedure. Multiple rounds of continuous stacking Hybridization considerably increase the efficiency of the Sequencing method, eventually approaching the power of (L+l)-matrix. We develop here an algorithm that allows us to minimize the number of additional Hybridization steps, by assembling sets of l-tuples to be added together in each round of continuous stacking Hybridization. For SHOM using a matrix of octanucleotides, continuous stacking Hybridization with pentanucleotides increases the length of unambiguously sequenced DNA from 200 to several thousands of base pairs.
Radoje Drmanac - One of the best experts on this subject based on the ideXlab platform.
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accurate whole genome Sequencing as the ultimate genetic test
Clinical Chemistry, 2015Co-Authors: Radoje Drmanac, Brock A Peters, George M Church, Clifford ReidAbstract:Featured Article: Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, et al. Human genome Sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 2010;327:78–81.4 Even 30 years ago, it was obvious that Sanger Sequencing had limited throughput, and a more efficient process could replace many tedious gene and genome mapping projects. It would take until the mid-2000s for massively parallel Sequencing (MPS)5 technologies to demonstrate they could overtake the Sanger Sequencing hegemony. Our paper was not the first description of a viable MPS technology, but it firmly established that human whole genome Sequencing (WGS) could be done affordably (
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combinatorial Sequencing by Hybridization analysis of the nf1 gene
Genetic Testing, 2006Co-Authors: Annalisa Schirinzi, Snezana Drmanac, Bruno Dallapiccola, Steve Huang, Kathryn Scott, Alessandro De Luca, Donald Swanson, Radoje Drmanac, Saul Surrey, Paolo FortinaAbstract:Neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders, is caused by mutations in the NF1 gene. A variety of methods are currently used in clinical settings to define disease-causing mutations. We describe microarray-based combinatorial Sequencing-by-Hybridization (cSBH), which overcomes some disadvantages associated with other techniques. Sequence readout of 2 kb was achieved on a single slide, with detection of base substitutions, insertions and small deletions. In addition, cSBH analysis of the entire NF1 gene demonstrates reproducibility, efficiency and reduced time; therefore, representing an alternative to extensive DNA sequence characterization.
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identification of apc gene mutations in colorectal cancer using universal microarray based combinatorial Sequencing by Hybridization
Human Mutation, 2004Co-Authors: Shannon Cowie, Snezana Drmanac, Steve Huang, Donald Swanson, Radoje Drmanac, Saul Surrey, Kathleen Delgrosso, Desiree Du Sart, Paolo FortinaAbstract:Familial adenomatous polyposis (FAP) is an autosomal dominant inherited form of colorectal cancer, caused mostly by mutations in the APC gene. Due to the wide variety of mutations found and the large size of the APC gene, several methods of mutation detection are used, which can be time consuming and costly. Here we demonstrate a new method of mutation detection in the APC gene using an array-based approach termed combinatorial Sequencing-by-Hybridization (cSBH). In cSBH, a universal probe set is attached to a support and a second one is in solution. Two-probe ligation occurs when a DNA strand from the target PCR product consecutively anneals to both unlabeled array-bound and solution-phase dye-labeled probe, creating all target-complementary long-labeled probes attached to the surface. A standard array reader scores fluorescent signals at each array position. Cell lines and patient DNA with known APC gene mutations were analyzed using a cSBH-based HyChip trade mark product. Results show that this universal hexamer (6-mer) chip can successfully detect a range of mutations. Results are very robust for a continuous readout of 3.6 kb from a PCR target, with 99.97% accuracy on a single HyChip trade mark slide. cSBH is a fast, cost-efficient method for first stage mutation screening in the APC or any other gene.
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Sequencing by Hybridization sbh advantages achievements and opportunities
Advances in Biochemical Engineering \ Biotechnology, 2002Co-Authors: Radoje Drmanac, Snezana Drmanac, Gloria Chui, Robert Diaz, Aaron Hou, Hui Jin, Paul Jin, Sunhee Kwon, Scott Lacy, Bill MoeurAbstract:Efficient DNA Sequencing of the genomes of individual species and organisms is a critical task for the advancement of biological sciences, medicine and agriculture. Advances in modern Sequencing methods are needed to meet the challenge of Sequencing such megabase to gigabase quantities of DNA. Two possible strategies for DNA Sequencing exist: direct methods, in which each base position in the DNA chain is determined individually (e.g., gel Sequencing or pyroSequencing), and indirect methods, in which the DNA sequence is assembled based on experimental determination of oligonucleotide content of the DNA chain. One promising indirect method is Sequencing by Hybridization (SBH), in which sets of oligonucleotides are hybridized under conditions that allow detection of complementary sequences in the target nucleic acid. The unprecedented sequence search parallelism of the SBH method has allowed development of high-throughput, low-cost, miniaturized Sequencing processes on arrays of DNA samples or probes. Newly developed SBH methods use DNA ligation to combine relatively small sets of short probes to score potentially tens of millions of longer oligonucleotide sequences in a target DNA. Such combinatorial approaches allow analysis of DNA samples of up to several kilobases (several times longer than allowed by current direct methods) for a variety of DNA sequence analysis applications, including de novo Sequencing, reSequencing, mutation/SNP discovery and genotyping, and expression monitoring. Future advances in biochemistry and implementation of detection methods that allow single-molecule sensitivity may provide the necessary miniaturization, specificity, and multiplexing efficiency to allow routine whole genome analysis in a single solution-based Hybridization experiment.
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accurate Sequencing by Hybridization for dna diagnostics and individual genomics
Nature Biotechnology, 1998Co-Authors: Snezana Drmanac, Ivan Labat, David Kita, Brian K Hauser, Carl J Schmidt, John D Burczak, Radoje DrmanacAbstract:Medical DNA diagnostics will increasingly rely on an accurate and inexpensive identification of mutations that affect the function of a gene. To validate diagnostic Sequencing by Hybridization (SBH), a number of p53 samples were analyzed with the complete set of 8192 noncomplementary 7-mer oligonu-cleotides. In four repeated, blind experiments we accurately sequenced 1.1 kb per each of 12 homozygote and heterozygote samples possessing base substitutions, insertions, and deletions. This SBH variant offers a high throughput platform to inexpensively sequence individual gene or pathogen genome samples within the clinical laboratory setting.
Mateu Yabar Valles - One of the best experts on this subject based on the ideXlab platform.
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an ant colony optimization algorithm for dna Sequencing by Hybridization
Computers & Operations Research, 2008Co-Authors: Christian Blum, Mateu Yabar Valles, Maria J BlesaAbstract:The reconstruction of DNA sequences from DNA fragments is one of the most challenging problems in computational biology. In recent years the specific problem of DNA Sequencing by Hybridization has attracted quite a lot of interest in the optimization community. Several metaheuristics such as tabu search and evolutionary algorithms have been applied to this problem. However, the performance of existing metaheuristics is often inferior to the performance of recently proposed constructive heuristics. On the basis of these new heuristics we develop an ant colony optimization algorithm for DNA Sequencing by Hybridization. An important feature of this algorithm is the implementation in a so-called multi-level framework. The computational results show that our algorithm is currently a state-of-the-art method for the tackled problem.
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new constructive heuristics for dna Sequencing by Hybridization
Workshop on Algorithms in Bioinformatics, 2006Co-Authors: Christian Blum, Mateu Yabar VallesAbstract:Deoxyribonucleic acid (DNA) Sequencing is an important task in computational biology. In recent years the specific problem of DNA Sequencing by Hybridization has attracted quite a lot of interest in the optimization community. However, in contrast to the development of metaheuristics, the work on simple constructive heuristics hardly received any attention. This is despite the fact that well-working constructive heuristics are often an essential component of succesful metaheuristics. It is exactly this lack of constructive heuristics that motivated the work presented in this paper. The results of our best constructive heuristic are comparable to the results of the best available metaheuristics, while using less computational resources.
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multi level ant colony optimization for dna Sequencing by Hybridization
Lecture Notes in Computer Science, 2006Co-Authors: Christian Blum, Mateu Yabar VallesAbstract:Deoxyribonucleic acid (DNA) Sequencing is an important task in computational biology. In recent years the specific problem of DNA Sequencing by Hybridization has attracted quite a lot of interest in the optimization community. This led to the development of several metaheuristic approaches such as tabu search and evolutionary algorithms. In this work we propose an ant colony algorithm to resolve this problem. In addition, we apply our algorithm within a multi-level framework which helps in significantly reducing the computation time. The results show that our algorithm is currently among the state-of-the-art methods for this problem.
Dekel Tsur - One of the best experts on this subject based on the ideXlab platform.
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Sequencing by Hybridization in few rounds
Journal of Computer and System Sciences, 2010Co-Authors: Dekel TsurAbstract: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 (1995) [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 (1995) [12] and Frieze and Halldorsson (2002) [8].
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Sequencing by Hybridization in few rounds
Lecture Notes in Computer Science, 2003Co-Authors: Dekel TsurAbstract:Sequencing by Hybridization (SBH) is a method for reconstructing an unknown DNA string based on substring queries: Using Hybridization experiments, one can determine for each string in a given set of strings, whether the string appears in the target string, and use this information to reconstruct the target string. We study the problem when the queries are performed in rounds, where the queries in each round depend on the answers to the queries in the previous rounds. We give an algorithm that can reconstruct almost all strings of length n using 2 rounds with O(n log α n/log α log α n) queries per round, and an algorithm that uses log α * n - Ω(1) rounds with O(n) queries per round, where α is the size of the alphabet. We also consider a variant of the problem in which for each substring query, the answer is whether the string appears once in the target, appears at least twice in the target, or does not appear in the target. For this problem, we give an algorithm that uses 3 rounds of O(n) queries. In all our algorithms, the lengths of the query strings are Θ(log α n). Our results improve the previous results of Margaritis and Skiena [17] and Frieze and Halldorsson [10].
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large scale Sequencing by Hybridization
Journal of Computational Biology, 2002Co-Authors: Ron Shamir, Dekel TsurAbstract:Sequencing by Hybridization 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. However, even with a Sequencing chip containing all 4(9) 9-mers and assuming no Hybridization errors, only about 400-bases-long sequences can be reconstructed unambiguously. Drmanac et al. (1989) suggested Sequencing long DNA targets by obtaining spectra of many short overlapping fragments of the target, inferring their relative positions along the target, and then computing spectra of subfragments that are short enough to be uniquely recoverable. Drmanac et al. do not treat the realistic case of errors in the Hybridization process. In this paper, we study the effect of such errors. We show that the probability of ambiguous reconstruction in the presence of (false negative) errors is close to the probability in the errorless case. More precisely, the ratio between these probabilities is 1 + O(p = (1 - p)(4). 1 = d) where d is the average length of subfragments, and p is the probability of a false negative. We also obtain lower and upper bounds for the probability of unambiguous reconstruction based on an errorless spectrum. For realistic chip sizes, these bounds are tighter than those given by Arratia et al. (1996). Finally, we report results on simulations with real DNA sequences, showing that even in the presence of 50% false negative errors, a target of cosmid length can be recovered with less than 0.1% miscalled bases.
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large scale Sequencing by Hybridization
Research in Computational Molecular Biology, 2001Co-Authors: Ron Shamir, Dekel TsurAbstract:Sequencing by Hybridization 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. However, even with a Sequencing chip containing all 49 9-mers and assuming no Hybridization errors, only about 400 bases-long sequences can be reconstructed unambiguously.Drmanac et al. suggested Sequencing long DNA targets by obtaining spectra of many short overlapping fragments of the target, inferring their relative positions along the target and computing spectra of subfragments that are short enough to be uniquely recoverable. Drmanac et al. do not treat the realistic case of errors in the Hybridization process. In this paper we study the effect of such errors. We show that the probability of ambiguous reconstruction in the presence of (false negative) errors is close to the probability in the errorless case. More precisely, the ratio between these probabilities is 1 + O(p/(1 - p)4 · 1/d) where d is the average distance between neighboring subfragments, and p is the probability of a false negative.We also obtain lower and upper bounds for the probability of unambiguous reconstruction based on errorless spectrum. For realistic chip sizes, these bounds are tighter than those given by Arratia et al. Finally, we report results on simulations with real DNA sequences, showing that even in the presence of 50% false negative errors, a target of cosmid length can be recovered with less than 0.1% miscalled bases.
Christian Blum - One of the best experts on this subject based on the ideXlab platform.
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an ant colony optimization algorithm for dna Sequencing by Hybridization
Computers & Operations Research, 2008Co-Authors: Christian Blum, Mateu Yabar Valles, Maria J BlesaAbstract:The reconstruction of DNA sequences from DNA fragments is one of the most challenging problems in computational biology. In recent years the specific problem of DNA Sequencing by Hybridization has attracted quite a lot of interest in the optimization community. Several metaheuristics such as tabu search and evolutionary algorithms have been applied to this problem. However, the performance of existing metaheuristics is often inferior to the performance of recently proposed constructive heuristics. On the basis of these new heuristics we develop an ant colony optimization algorithm for DNA Sequencing by Hybridization. An important feature of this algorithm is the implementation in a so-called multi-level framework. The computational results show that our algorithm is currently a state-of-the-art method for the tackled problem.
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new constructive heuristics for dna Sequencing by Hybridization
Workshop on Algorithms in Bioinformatics, 2006Co-Authors: Christian Blum, Mateu Yabar VallesAbstract:Deoxyribonucleic acid (DNA) Sequencing is an important task in computational biology. In recent years the specific problem of DNA Sequencing by Hybridization has attracted quite a lot of interest in the optimization community. However, in contrast to the development of metaheuristics, the work on simple constructive heuristics hardly received any attention. This is despite the fact that well-working constructive heuristics are often an essential component of succesful metaheuristics. It is exactly this lack of constructive heuristics that motivated the work presented in this paper. The results of our best constructive heuristic are comparable to the results of the best available metaheuristics, while using less computational resources.
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multi level ant colony optimization for dna Sequencing by Hybridization
Lecture Notes in Computer Science, 2006Co-Authors: Christian Blum, Mateu Yabar VallesAbstract:Deoxyribonucleic acid (DNA) Sequencing is an important task in computational biology. In recent years the specific problem of DNA Sequencing by Hybridization has attracted quite a lot of interest in the optimization community. This led to the development of several metaheuristic approaches such as tabu search and evolutionary algorithms. In this work we propose an ant colony algorithm to resolve this problem. In addition, we apply our algorithm within a multi-level framework which helps in significantly reducing the computation time. The results show that our algorithm is currently among the state-of-the-art methods for this problem.
