In vitro selection of non-crosshybridizing oligonucleotides for computation

Since they minimize errors from cross-hybridizations, DNA oligonucleotides that annealas designed are beneficial to DNA computing. By in vitro selection, huge libraries of non-crosshybridizing oligonucleotides might be evolved in the test tube. As a first step, a fitness function corresponding to non-crosshybridization was based upon the duplex stability of randomly matched oligonucleotides. By melting pairs that have a low thermal stability, a protocol based on DNA polymerization selectively amplifies maximally mismatched oligonucleotides over those that were more closely matched. Experiments confirmed this property of the protocol, and in addition, a reaction temperature window was identified in which discrimination between matched and mismatched might be obtained. The protocol was iterated on a set of random starting material, and there was evidence that non-crosshybridizing libraries were in fact being created. These results are a step toward practical manufacture of very large libraries of non-crosshybridizing oligonucleotides in the test tube. This revised version was published online in June 2006 with corrections to the Cover Date.     

DNA计算与DNA计算机研究进展与展望

DNA computing is a new method based on biochemical reactions and molecular biology technology.The paper first introduces the basic principle and advantages of DNA computing, and then surveys DNA computing and DNA computer, finally, points out current existing problems and future search directions of DNA computing and DNA computer.     

DNA分子计算模型

The field of practical DNA computing opened in 1994 with Adleman's paper,in which a laboratory experi-ment involving DNA molecules was used to solve a small instance of the Hamiltonian Path problem. The characteris-tic of this computation is its powerful ability in parallelism,its huge storage and high energy efficiency. This paper mainly introduces the principles of DNA computing and the sticker computing model.     

How ciliates manipulate their own DNA – A splendid example of natural computing

DNA computing is a novel and vivid researcharea which is genuinely interdisciplinary –computer scientists and molecular scientistscollaborate to investigate the use of DNAmolecules for the purpose of computing. DNAcomputing in vivo is the investigation ofcomputations taking place naturally in a livingcell, with the goal of understandingcomputational properties of DNA molecules intheir native environment. Gene assembly inciliates (single cell organisms) is perhaps themost involved process of DNA manipulation yetknown in living organisms. The computationalnature of this process has attracted muchattention in recent years. The resultsobtained so far demonstrate that this processof gene assembly is a splendid example ofcomputing taking place in nature, i.e., NaturalComputing. Indeed, DNA computing in vivomay be far more widespread in nature than wecurrently recognize. This paper is a tutorialon (computational nature of the) gene assemblyin ciliates, which is intended for a broadaudience of researchers interested in NaturalComputing. In particular, no knowledge ofmolecular biology is assumed on the part of themotivated reader.     

Characterization of Non-crosshybridizing DNA Oligonucleotides Manufactured in vitro

Libraries of DNA oligonucleotides manufactured by an in vitro selection protocol were characterized for their non-crosshybridizing properties. Cloning and sequencing after several iterations of the protocol showed that the sequences, in general, became more non-crosshybridizing. Gel electrophoresis of protocol product, also, indicated non-crosshybridization, and showed evolution in the population of molecules under the non-crosshybridization selection pressure. Melting curves of protocol product also indicated non-crosshybridization when compared to control samples. Thus, it appears that the protocol does select populations of non-crosshybridizing sequences.     

DNA计算中核酸序列设计方法比较研究

DNA计算是将现实问题进行编码,映射到DNA分子上,然后通过分子生物实验产生出代表问题解的DNA分子,最后通过检测技术提取出该DNA分子．高质量的DNA编码可以尽可能避免或减少计算过程中出现的错误,并使检测阶段易于提取出代表问题解的DNA分子．文中对基于汉明距离和基于自由能的DNA核酸编码方法进行研究,分析了两类方法的约束条件对DNA编码质量的影响,比较了两类方法排除非特异性杂交的完备性和计算量,进一步分析了两类方法编码DNA序列的效率．通过分析和比较得到,两类DNA计算编码方法都能有效地限制DNA分子间的非特异性杂交,其中基于汉明距离的DNA编码方法的计算量比较小,但是它仅能近似地估计DNA分子间杂交的热力学稳定性,不能完全替代最小自由能的编码方法．在满足DNA计算试验精度要求的条件下,采用基于汉明距离的DNA编码设计方法不仅能有效地的挑选出特异性杂交和非特异性杂交的DNA序列,还能有效地减少计算量,从而提高DNA序列设计的效率．     

DNA计算中突变误差的纠正

文章重点讨论了在DNA计算中突变误差的处理问题,其中包括突变误差的数据空间、突变误差的自动纠正和纠错码在DNA操作系统设计中的应用问题。并在分析突变误差数据空间、突变误差纠错码的基础上,提出了解决DNA计算中突变误差问题的方案。     

Automated selection of aminoglycoside aptamers

The in vitro selection of aptamers that bind to low molecular weight targets is commonly a tedious, time-consuming project. We have expanded current automated selection protocols to include aptamer selections against small molecules including the aminoglycosides neomycin, kanamycin, and tobramycin. This modified procedure decreases both the frequency of manual handling of the selection reagents and the time required to perform the experiment, generating aptamers against the chosen target at a much greater rate. Using this process, we have selected aptamers of good affinity against all three aminoglycosides chosen. The method is suitable for integration with high-throughput technologies, greatly expanding the possibility of discovering useful aptamers against other low weight targets.     

基于质粒的DNA计算模型研究

论文给出了一种基于环状质粒DNA计算的新方法,这种计算质粒包含一个特殊的插入DNA序列片断,每个片断定位在匹配的限制性内切位点,通过剪切和粘贴实现计算过程。论文同时给出了生物计算模型和相关的数学描述,这种模式的计算有待进一步研究。     

Language-theoretic aspects of DNA complematarity

The optimism about the possibilities of DNA computing is based on two central issues: the Watson–Crick complementarity and the massive parallelism of DNA strands. While the latter issue renders exhaustive searches possible and thus may settle problems previously considered intractable, the former issue is the cause behind the universality of many models of DNA computing. Moreover, complementarity can be viewed as a purely language-theoretic operation: undesirable circumstances in a string trigger a transition to the complementary string. This aspect of complementarity is investigated in the present paper, mainly from the point of view of L systems. New types of word sequences will be discovered. Sometimes the resulting decision problems are equivalent to well-known open problems from other areas.     

利用脱氧核酶调控基因表达的DNA计算模型研究(英文)

用于逻辑调控基因表达分子自动机的研究是DNA计算的重要研究领域．文中将脱氧核酶技术应用于DNA计算研究当中,利用脱氧核酶的特性,特别是可以作为反义药物的特点,作为构建分子自动机的主要材料,设计了调控基因H—ras表达的DNA计算模型,而且模型也可适用于其它过表达基因的调控．结合DNA计算具备的高度并行性和智能性的优点,该模型为DNA计算在基因表达调控方面的应用做了进一步探索．     

DAD计算中的遍历理论模型及算法

该文源于DNA序列杂交先后顺序的工程计算问题。在杂交先后顺序(SHB)问题中,人们试图想通过首先确定在一个很长的DNA字符串S中出现的k-长子串来了解整个原始的字符串S,通过研究k-长子串的重叠模式来重新构造原始的字符串S。该文将SHB问题转化为具体的图论问题。根据图及其线图的关系,部分解决了上述SHB问题的等价形式,即在有向线图顶点的入度和出度不超过2的情形下,用遍历理论为SHB问题建立了数学模型,从而能在多项式时间内找到有向线图的哈密顿路或圈。文章最后,指出了须进一步研究的问题。     

Application of Mismatch Detection Methods in DNA Computing

In many implementations of DNA computing, reliable detection of hybridization is of prime importance. We have applied several well-established DNA mutation scanning methods to this problem. Since they have been developed for speed and accuracy, these technologies are very promising for DNA computing. We have benchmarked a heteroduplex migration assay and enzymatic detection of mismatches on a 4 variable instance of 3SAT, using a previously described blocking algorithm. The first method is promising, but yielded ambiguous results. On the other hand, we were able to distinguish all perfect from imperfect duplexes by means of a CEL I mismatch endonuclease assay.     

插入/切割DNA计算系统模型研究

为建立以载体分子为基础的DNA计算系统,根据目的基因和载体分子连接操作的特性构造一类DNA计算模型.该模型基于上下文的插入/删除模型,将线性分子拓展到环形质粒分上进行讨论.以剪接系统理论为基础,对在单一限制性内切酶作用下的插入/切割操作进行模拟.最后证明了这类操作的图灵机表达能力.     

DNA计算中荧光技术的应用及其发展

DNA计箅作为前沿科学研究的重点和热点.已经从简单发展为复杂,从理论转化为应用.在这一过程中,反应速度快、变化灵敏的荧光标记技术发挥了重要的作用.文中围绕DNA计算和荧光标记技术两个方面进行说明.一方面,对近年来DNA计算中荧光技术的应用进行了总结:(1)荧光标记的表面计算;(2)与某些切技术相结合的荧光检测;(3)与DNA链置换相结合的荧光技术;(4)与基因沉默技术相结合的荧光DNA逻辑门;(5)与DNA自组装立体结构相结合的荧光技术;(6)与DNA变构相结合的荧光技术.另一方面,介绍了几种近年来发展起来的新型荧光技术:(1)荧光信号识别放大技术;(2)与磁珠技术相结合的荧光技术;(3)与PH值变化相结合的DNA荧光技术;(4)与miRNAs检测相结合的荧光技术.在今后的研究中,只有将这两者紧密结合,才能发挥DNA计算天然的优势.     

计算科学的新领域：DNA计算（Ⅰ）

DNA计算是应用分子生物技术进行计算的新方法。从理论上研究DNA计算方法，有利于推动理论计算科学的发展。本系列文章应用形式语言及自动机理论技术，系统地探讨了DNA分子的可计算性及其计算能力。本文主要介绍常用DNA分子操作方法，并根据DNA分子的结构及特点，给出了DNA分子的形式化描述。     

DNA计算虚拟生物实验室设计

为了对生物实验中的反应产物进行分析、解释以及跟踪，并对实验结果进行预测，该文介绍了一个仿真生物反应的工具——虚拟生物实验室Virtual Bio—Lab（简称VBL）。在VBL中定义了一个包括聚合酶连锁反应、连接、杂交，熔化和电泳等模块在内的框架，每个模块实现一个基本的生物操作，各模块之间通过传递DNA“溶液”进行通信。使用合理的简化假设，VBL能在较短时间内实现对任意序列DNA生物操作的仿真。如有向哈密顿路径问题的DNA计算解决方案仿真。在实际应用中，VBL可以帮助验证DNA计算的理论模型，提高生物实验效率。     

DNA计算模型及应用综述

自从Adleman博士最早利用DNA计算成功求解了7个顶点有向图的Hamilton问题以来,DNA计算[1]被引入多个研究领域,成为当今科技发展的热点之一。首先介绍DNA计算的基本原理及编码方法,其次阐述了DNA计算的主要模型,再次总结了国内外研究学者应用DNA计算解决的实际问题,最后列举了DNA计算改进的相关方向。     

DNA计算中的编码方法研究

DNA计算是一种利用生物大分子间的相互作用来实现并行计算的新的计算模式。因为其具有强大的并行性和高密度的信息存储能力,因而引起了科学界的广泛关注。编码是DNA计算的第一步,也是最重要的一步。编码质量的好坏直接影响反应过程的速度和效率。论文主要介绍了DNA计算过程中的编码问题、影响编码的因素及已有的几种主要的编码方法;最后指出了DNA计算的编码方法存在的问题及研究方向。     

DNA计算的原理及研究进展

阐述了DNA计算的机理及其数学原理,介绍了Adleman实验,指出了DNA计算目前的应用领域和存在的问题,并对DNA计算的发展前景进行了展望。