A CLIQUE algorithm using DNA computing techniques based on closed-circle DNA sequences

DNA computing has been applied in broad fields such as graph theory, finite state problems, and combinatorial problem. DNA computing approaches are more suitable used to solve many combinatorial problems because of the vast parallelism and high-density storage. The CLIQUE algorithm is one of the gird-based clustering techniques for spatial data. It is the combinatorial problem of the density cells. Therefore we utilize DNA computing using the closed-circle DNA sequences to execute the CLIQUE algorithm for the two-dimensional data. In our study, the process of clustering becomes a parallel bio-chemical reaction and the DNA sequences representing the marked cells can be combined to form a closed-circle DNA sequences. This strategy is a new application of DNA computing. Although the strategy is only for the two-dimensional data, it provides a new idea to consider the grids to be vertexes in a graph and transform the search problem into a combinatorial problem.     

DNA as a ‘Nanomaterial’

DNA is recognized as a nanomaterial, not as a biological material, in the research field of nanotechnology. This article reviews recent research on nanowires, nanoarchitectures, computing, aptamers, biocatalysts, devices, and machines using DNA. In these works, the characteristics of DNA including facile synthesis by the solid-phase method, self-assembly, electro-conductivity, information elements, amplification, switching, molecular recognition, and catalytic functions, were appropriately applied. Multiple functions of DNA could be used simultaneously, and activated independently, by molecular switching. Therefore, the combinations of functional sequences of DNA can produce unique materials. It is obvious that the DNA molecule is one of the most promising functional nanomaterials. However, the application of DNA molecules is still under study because of the big gap that exists between theory and practice. We eagerly anticipate a ‘coming out’ of DNA due to breakthroughs in nanobiotechnology.     

Detecting recombination in 4-taxa DNA sequence alignments with Bayesian hidden Markov models and Markov chain Monte Carlo

This article presents a statistical method for detecting recombination in DNA sequence alignments, which is based on combining two probabilistic graphical models: (1) a taxon graph (phylogenetic tree) representing the relationship between the taxa, and (2) a site graph (hidden Markov model) representing interactions between different sites in the DNA sequence alignments. We adopt a Bayesian approach and sample the parameters of the model from the posterior distribution with Markov chain Monte Carlo, using a Metropolis-Hastings and Gibbs-within-Gibbs scheme. The proposed method is tested on various synthetic and real-world DNA sequence alignments, and we compare its performance with the established detection methods RECPARS, PLATO, and TOPAL, as well as with two alternative parameter estimation schemes.     

基于质粒DNA匹配问题的分子算法

给定无向图,图的最小极大匹配问题是寻找每条边都不相邻的最大集中的最小者,这个问题是著名的NP-完全问题.1994年Adleman博士首次提出用DNA计算解决NP-完全问题,以编码的DNA序列为运算对象,通过分子生物学的运算操作解决复杂的数学难题,使得NP-完全问题的求解可能得到解决.提出了基于质粒DNA的无向图的最大匹配问题的DNA分子生物算法,通过限制性内切酶的酶切和凝胶电泳完成解的产生和最终接的分离,依据分子生物学的实验手段,算法是有效并且可行的.     

Phylogeographic genomics of mitochondrial DNA: Highly-resolved patterns of intraspecific evolution and a multi-species, microarray-based DNA sequencing strategy for biodiversity studies

Phylogeographic genomics, based on multiple complete mtDNA genome sequences from within individual vertebrate species, provides highly-resolved intraspecific trees for the detailed study of evolutionary biology. We describe new biogeographic and historical insights from our studies of the genomes of codfish, wolffish, and harp seal populations in the Northwest Atlantic, and from the descendants of the founding human population of Newfoundland. Population genomics by conventional sequencing methods remains laborious. A new biotechnology, iterative DNA “re-sequencing”, uses a DNA microarray to recover 30–300 kb of contiguous DNA sequence in a single experiment. Experiments with a single-species mtDNA microarray show that the method is accurate and efficient, and sufficiently species-specific to discriminate mtDNA genomes of moderately-divergent taxa. Experiments with a multi-species DNA microarray (the “ArkChip”) show that simultaneous sequencing of species in different orders and classes detects SNPs within each taxon with equal accuracy as single-species-specific experiments. Iterative DNA sequencing offers a practical method for high-throughput biodiversity genomics that will enable standardized, coordinated investigation of multiple species of interest to Species at Risk and conservation biologists.     

Hybridization on squashed flies: A method to detect gene sequences in individual Drosophila

Specific gene sequences can be detected by DNA hybridization to individual Drosophila squashed on cellulose or nylon filters. This “squash-blot” method permits the rapid survey of DNA polymorphism in large Drosophila population samples. It could also be useful for studying chromosome aberrations, departure from diploidy, and detection of pathogenic agents in vector insects.     

A P system and a constructive membrane-inspired DNA algorithm for solving the Maximum Clique Problem

We present a P system with replicated rewriting to solve the Maximum Clique Problem for a graph. Strings representing cliques are built gradually. This involves the use of inhibitors that control the space of all generated solutions to the problem. Calculating the maximum clique for a graph is a highly relevant issue not only on purely computational grounds, but also because of its relationship to fundamental problems in genomics. We propose to implement the designed P system by means of a DNA algorithm. This algorithm is then compared with two standard papers that addressed the same problem and its DNA implementation in the past. This comparison is carried out on the basis of a series of computational and physical parameters. Our solution features a significantly lower cost in terms of time, the number and size of strands, as well as the simplicity of the biological implementation.     

Topoisomerase II Regulates the Maintenance of DNA Methylation

The maintenance of DNA methylation in nascent DNA is a critical event for numerous biological processes. Following DNA replication, DNMT1 is the key enzyme that strictly copies the methylation pattern from the parental strand to the nascent DNA. However, the mechanism underlying this highly specific event is not thoroughly understood. In this study, we identified topoisomerase IIα (TopoIIα) as a novel regulator of the maintenance DNA methylation. UHRF1, a protein important for global DNA methylation, interacts with TopoIIα and regulates its localization to hemimethylated DNA. TopoIIα decatenates the hemimethylated DNA following replication, which might facilitate the methylation of the nascent strand by DNMT1. Inhibiting this activity impairs DNA methylation at multiple genomic loci. We have uncovered a novel mechanism during the maintenance of DNA methylation.     

Nitric Oxide Induction of Neuronal Endonuclease Activity in Programmed Cell Death

Neuronal survival is intricately linked to the maintenance of intact DNA. In contrast, neuronal degeneration following nitric oxide (NO) exposure is dependent, in part, on the degradation of DNA through programmed cell death (PCD). We therefore investigated in primary rat hippocampal neurons the role of endogenous deoxyribonucleases, enzymes responsible for metabolically derived DNA cleavage, during NO-induced neurodegeneration. Twenty-four hours following exposure to the NO generators sodium nitroprusside (300 μM) and SIN-1 (300 μM), neuronal survival was reduced from approximately 88 to 23%. Treatment with aurintricarboxylic acid (1–100 μM), an endonuclease inhibitor, during NO exposure increased neuronal survival from 23 to 80% and decreased DNA fragmentation from 70 to 30% over a 24-h period. Enhancement of endonuclease activity alone with zinc chelation actively decreased neuronal survival from approximately 80% to approximately 34%. DNA digestion assays identified not only two constitutively active endonucleases, an acidic endonuclease (pH 4.0–7.0) and a calcium/magnesium-dependent endonuclease (pH 7.2–8.0), but also a NO-inducible magnesium-dependent endonuclease (pH 8.0). In the absence of endonuclease activity, DNA degradation did not occur during NO application, suggesting that endonuclease activity was a requisite pathway for NO-induced PCD. In addition, NO independently altered intracellular pH in ranges that were physiologically relevant for the activity of the endonucleases responsible for DNA degradation. Our identification and characterization of specific neuronal endonucleases suggest that the constitutive endonucleases may play a role in the initial stages of NO-induced PCD, but the subsequent “downstream” degradation of DNA may ultimately be dependent upon the NO-inducible endonuclease.     

A new fast algorithm for solving the minimum spanning tree problem based on DNA molecules computation

The minimum spanning tree (MST) problem is to find minimum edge connected subsets containing all the vertex of a given undirected graph. It is a vitally important NP-complete problem in graph theory and applied mathematics, having numerous real life applications. Moreover in previous studies, DNA molecular operations usually were used to solve NP-complete head-to-tail path search problems, rarely for NP-hard problems with multi-lateral path solutions result, such as the minimum spanning tree problem. In this paper, we present a new fast DNA algorithm for solving the MST problem using DNA molecular operations. For an undirected graph with n vertex and m edges, we reasonably design flexible length DNA strands representing the vertex and edges, take appropriate steps and get the solutions of the MST problem in proper length range and O(3m + n) time complexity. We extend the application of DNA molecular operations and simultaneity simplify the complexity of the computation. Results of computer simulative experiments show that the proposed method updates some of the best known values with very short time and that the proposed method provides a better performance with solution accuracy over existing algorithms.     

DNA Nano-Gears

DNA is a nanoscale material for programmable self-assembly, using the selective affinity of pairs of DNA strands to form DNA nanostructures. Self-assembly is the spontaneous self-ordering of substructures into superstructures which driven by the selective affinity of the substructures. DNA self-assembly is the most advanced and versatile system that has been experimentally demonstrated for programmable construction of patterned systems on the molecular scale. This programmability renders the scaffolding have the patterning required for fabricating complex devices made of these components. We present various strategies to assemble DNA based gears for application in nano-machines, nano-motors and nano-devices. In this paper, some fundamental parts of mechanical nano-machines with DNA blocks are designed. These kinds of nanostructures, nano-gears, are fundamental for the development of future useful molecular-level devices.     

DNA-binding geometry dependent energy transfer from 4′,6-diamidino-2-phenylindole to cationic porphyrins

The circular and linear dichroism (CD and LD) spectral properties of the meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP)–DNA complex at a [porphyrin]/[DNA] ratio below 0.015 showed that TMPyP intercalates between DNA base pairs. Contrarily, when cis–bis(N-methylpyridinium-4-yl)porphyrin (BMPyP) is associated with DNA, no CD spectrum was induced and a bisignate LD spectrum was observed. These spectral properties of both the TMPyP and BMPyP were essentially retained when the minor groove of the DNA was saturated with 4′,6-diamidino-2-phenylindole (DAPI). The fluorescence of the DNA-bound DAPI was effectively quenched by BMPyP and TMPyP. The quenching by BMPyP can be described through a pure static mechanism while TMPyP quenching produced an upward bending curve in the Stern–Volmer plot. Quenching efficiency was by far greater than predicted by the “sphere of action model”, suggesting that the DNA provides some additional processes for an effective energy transfer.     

Nano-sandwich composite by kinetic trapping assembly from protein and nucleic acid

Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA–DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein–RNA–DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.     

Recovery of DNA barcodes from blackfly museum specimens (Diptera: Simuliidae) using primer sets that target a variety of sequence lengths

In this study, we evaluated the efficacy of various primers for the purpose of DNA barcoding old, pinned museum specimens of blackflies (Diptera: Simuliidae). We analysed 271 pinned specimens representing two genera and at least 36 species. Due to the age of our material, we targeted overlapping DNA fragments ranging in size from 94 to 407 bp. We were able to recover valid sequences from 215 specimens, of which 18% had 500‐ to 658‐bp barcodes, 36% had 201‐ to 499‐bp barcodes and 46% had 65‐ to 200‐bp barcodes. Our study demonstrates the importance of choosing suitable primers when dealing with older specimens and shows that even very short sequences can be diagnostically informative provided that an appropriate gene region is used. Our study also highlights the lack of knowledge surrounding blackfly taxonomy, and we briefly discuss the need for further phylogenetic studies in this socioeconomically important family of insects.     

DNA计算的发展现状及未来展望

随着高性能计算需求的不断增长,传统计算模式面临着前所未有的巨大挑战.在众多新兴计算技术中,DNA计算系统以其低能耗、并行化等特点而广受关注.DNA电路(DNA circuit)是实现DNA计算的基础,也是该领域重要的分子信息调控和处理技术.文中重点介绍了DNA计算的基本原理,并总结了最新的研究进展,最后讨论了基于DNA...     

Light scattering study of natural DNAs over a wide range of molecular weights: Evidence for compaction of the large molecules

This work reports light scattering measurements on DNA in aqueous solutions (100 mM NaCl, 1 mM EDTA and 10 mM Tris–HCl buffer, pH 7.8) over a wide range of molecular weights (10²–10⁵ base pairs) and shows that, in the above standard solvent, shorter chains (<10⁴ base pairs) behave as a “wormlike chain” and their diffusion coefficients as obtained by dynamic light scattering measurements, confirm the prediction of standard wormlike model, whilst longer chains (>10⁴ base pairs) behave in a different manner. Dynamic and static light scattering and SEM analysis indicate that DNA molecules 10⁵ base pairs long, condense into compact structures in our solvent conditions. Calculations done using a wormlike model are also presented and discussed in comparison both to our experimental data and to other data reported in the literature.     

Computing with DNA by operating on plasmids

A new method of computing using DNA plasmids is introduced and the potential advantages are listed. The new method is illustrated by reporting a laboratory computation of an instance of the NP-complete algorithmic problem of computing the cardinal number of a maximal independent subset of the vertex set of a graph. A circular DNA plasmid, specifically designed for this method of molecular computing, was constructed. This computational plasmid contains a specially inserted series of DNA sequence segments, each of which is bordered by a characteristic pair of restriction enzyme sites. For the computation reported here, the DNA sequence segments of this series were used to represent the vertices of the graph being investigated. By applying a scheme of enzymatic treatments to the computational plasmids, modified plasmids were generated from which the solution of the computational problem was selected. This new method of computing is applicable to a wide variety of algorithmic problems. Further computations in this style are in progress.     

Sequence specificity of cytosine methylation in the DNA of the Chinese hamster ovary (CHO-K1) cell line

We have determined the DNA renaturation kinetics for those DNA sequences of the Chinese hamster ovary (CHO-K1) cells in which enzymatic cytosine methylation occurred immediately after strand synthesis and for those in which methylation was delayed after strand synthesis. DNA sequences showing immediate or delayed methylation were found to be distributed throughout all repetition classes of the DNA of these cells, with a slight concentration of immediate methylation in moderately repetitive sequences and with delayed methylation being slightly over-represented in the highly repetitive fraction. However, DNA sequences showing both classes of methylation were represented equally in unique DNA sequences. We interpret these data to mean that the methylase acting near the replication forks (the ‘immediate’ methylase) is a relatively inefficient enzyme, missing some 20% of hemimethylated sites produced by DNA replication in these cells. We suggest that the methylase performing maintenance methylation at sites remote from the replication forks (the ‘delayed’ methylase) is simply a back-up enzyme for the first and that it has no true sequence specificity. The implications of this for the function(s) of DNA methylation in mammalian cells are discussed.