Wojciech T. Markiewicz

DNA sequencing with positive and negative errors.

The problem addressed in this paper is concerned with DNA sequencing by hybridization. An algorithm is proposed that solves a computational phase of this approach in the presence of both positive and negative errors resulting from the hybridization experiment. No a priori knowledge of the nature and source of these errors is required. An extensive set of computational experiments showed that the algorithm behaves surprisingly well if only positive errors appear. The general case, where positive and negative errors occur, can be also solved satisfactorily for an error rate up to 10%.

Tabu search for DNA sequencing with false negatives and false positives

Abstract The paper deals with the problem of DNA (deoxyribonucleic acid) sequencing by hybridization. A computational phase of this approach, i.e. a construction of a DNA sequence from oligonucleotides, is NP-hard in the strong sense in case of errors. Thus, since the last problem does not admit a polynomial time solution, a need arises to construct efficient heuristics solving the problem. In the paper, such a heuristic algorithm based on tabu search is proposed. Computational tests have proved its low complexity and high accuracy for both types of errors: false negatives and false positives.

Construction of DNA restriction maps based on a simplified experiment

MOTIVATION A formulation of a new problem of the restriction map construction based on a simplified digestion experiment and a development of an algorithm for solving both ideal and noisy data cases of the introduced problem. RESULTS A simplified partial digest problem and a branch and cut algorithm for finding the solution of the problem.

Sequencing by hybridization with isothermic oligonucleotide libraries

The problem addressed in this paper is concerned with DNA sequencing by hybridization. A new type of oligonucleotide libraries is proposed for hybridization experiments. The libraries consist of oligonucleotides of different length dependent on an oligonucleotide A(T) and C(G) content in such a way that an increment of C(G) is twice of that of A(T) and the sum of increments for each oligonucleotide is constant for a library. The latter is called an isothermic oligonucleotide library and the way of its construction will be presented. It will be shown that two such libraries that differ in their sums of increments by an A(T) increment are sufficient for DNA sequencing by hybridization. The hybridization experiment using isothermic oligonucleotide libraries should supply data with a lower number of errors due to the expected similarity of melting temperatures of oligonucleotide duplexes, thus, offering more stable conditions of the hybridization experiment. The combinatorial part of the general problem of DNA sequencing (allowing all kinds of errors) with isothermic libraries will be then formulated, and the ways of solving it will be shown. The general problem will be proved to be strongly NP-hard, but heuristic algorithms solving this problem are reported to have better computational features than those for standard libraries.

Tabu search algorithm for DNA sequencing by hybridization with isothermic libraries

In this paper, a problem of isothermic DNA sequencing by hybridization (SBH) is considered. In isothermic SBH a new type of oligonucleotide libraries is used. The library consists of oligonucleotides of different lengths depending on an oligonucleotide content. It is assumed that every oligonucleotide in such a library has an equal melting temperature. Each nucleotide adds its increment to the oligonucleotide temperature and it is assumed that A and T add 2 degrees C and C and G add 4 degrees C. The hybridization experiment using isothermic libraries should provide data with a lower number of errors due to an expected similarity of melting temperatures. From the computational point of view the problem of isothermic DNA sequencing with errors is hard, similarly like its classical counterpart. Hence, there is a need for developing heuristic algorithms that construct good suboptimal solutions. The aim of the paper is to propose a heuristic algorithm based on tabu search approach. The algorithm solves the problem with both positive and negative errors. Results of an extensive computational experiment are presented, which prove the high quality of the proposed method.

Synthesis of 5′-O-Dimeth0Xytrityl-4-N-/6-Trifluoroacetamidohexyl/-2′-Deoxycytidine and its Application in the Synthesis of Biotin-Labeled Oligonucleotides

Abstract 5′3′-O-protected 4-N-tosyl-2′-deoxycyt id ine was converted with 1,6-diaminohexane to 4-N-/6-ami nohexyl/-2′-deoxycyt id i ne and then into 5′-0-d imethoxytr i ty 1 -k-N-/(-tr if luoroacetamidohexyl 1–2 ′-deoxycyt id ine, The latter was used to prepare oligonucleotides by the phosphoramidite approach. Deprotected oligomers were labeled with biotin.

The reaction of 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane with some open chain polyhydroxy compounds

Abstract 1,3-Dichloro-1,1,3,3-tetraisopropyldisiloxane (I) forms an 8-membered ring (IIIa) with glycerol, a 7-membered ring (Va) with D-erythropentose phenylosazone (IV) and linear polymers with 1,4-butanediol resp.

Synthetic oligonucleotide combinatorial libraries and their applications.

The application of synthetic oligonucleotide combinatorial libraries is described in the studies of triplex DNA. A new method of selection of dispersed (beaded) oligonucleotide combinatorial libraries based on the use of streptavidin magnetic beads is presented. A combinatorial chemistry approach is also proposed for studies of polyaminooligonucleotides.

Synthetic Oligonucleotide Combinatorial Libraries. 3. Synthesis of Polyamevonucleosides

Abstract Synthesis of polyamino-2′-deoxynucleosides was studied. A synthesis of 2′-deoxyadenosine and 2′-deoxyguanosine derivatives carrying a protected spermine moiety at N-6 and N-2 positions respectively is described using unprotected polyamines as substrates. The question of reactivity of primary and secondary amino groups present in polyamines was studied. The evidence that only primary amino groups react with the synthesised precursors was accomplished from experiments with a secondary amine (di-n-butylamine). An approach to analyse properties of polyaminooligonucleotides using their synthetic combinatorial libraries is discussed.

Algorithm: Dealing with repetitions in sequencing by hybridization

DNA sequencing by hybridization (SBH) induces errors in the biochemical experiment. Some of them are random and disappear when the experiment is repeated. Others are systematic, involving repetitions in the probes of the target sequence. A good method for solving SBH problems must deal with both types of errors. In this work we propose a new hybrid genetic algorithm for isothermic and standard sequencing that incorporates the concept of structured combinations. The algorithm is then compared with other methods designed for handling errors that arise in standard and isothermic SBH approaches. DNA sequences used for testing are taken from GenBank. The set of instances for testing was divided into two groups. The first group consisted of sequences containing positive and negative errors in the spectrum, at a rate of up to 20%, excluding errors coming from repetitions. The second group consisted of sequences containing repeated oligonucleotides, and containing additional errors up to 5% added into the spectra. Our new method outperforms the best alternative procedures for both data sets. Moreover, the method produces solutions exhibiting extremely high degree of similarity to the target sequences in the cases without repetitions, which is an important outcome for biologists. The spectra prepared from the sequences taken from GenBank are available on our website http://bio.cs.put.poznan.pl/.