The frequency of oligonucleotides in mammalian genic regions

The large body of nucleic acid sequence data now available offers a unique opportunity for the characterization of individual oligonucleotides which may be specific to sequence functional domains. We have prepared algorithms for the study of the frequency distribution of all oligonucleotides of length 2-6 in DNA sequences. We have implemented them in the study of 634 mammalian DNA sequences spanning 1.782 Mb, and have obtained the distribution of the ratio between the observed frequency of oligonucleotides and their expected frequency based on independent nucleotide probabilities. We then studied the distribution of oligonucleotides (or k-tuples) of each length in a subset of 129 complete mammalian genes spanning 0.607 Mb. Eight distinct genomic regions, namely 5'-non-transcribed, first exon, first intron, intermediate exons, intermediate introns, last intron, last exon and 3'-non-transcribed, were considered. We observed that some oligonucleotides show a statistical behaviour and a regional distribution similar to that of known signal sequences. Moreover the frequency distribution of oligonucleotides of length 5 and 6 tends to become bimodal, indicating the existence of a population of very frequent oligonucleotides.     

Multiplexed spectral coding for simultaneous detection of DNA hybridization reactions based on FRET

Fluorescence resonance energy transfer (FRET) is widely used in spectral codification of information at the molecular level, and can be used to generate several layers of information on a DNA chip. We used two oligonucleotides (probes) labeled with different donor (harvesting) molecules in hybridization experiments with complementary oligonucleotides labeled with four different acceptors (targets). By looking at the fluorescence response of the sample after “specific” excitation of each donor molecule (by “specific” we mean a wavelength where one of the donors is predominantly excited), we inspected the possibility to identify the complementary oligonucleotide hybridized to the probe, in mixtures containing two donor probe/acceptor target pairs. In most samples (13 out of the 16 possible), it is trivial to identify the complementary target that is hybridized to the excited donor probe in the mixtures. The major limitations of the chosen system arise when very different concentrations of donor probe/acceptor target pairs are present in the same sample.     

BioSeg：一个生物序列数据模型

生物序列数据的表达和存储是生物序列数据处理的关键。当前的数据库管理系统不能有效地支持生物序列数据类型和操作,人们不得不用文本数据类型或直接使用文本文件存储生物序列数据。这种状况造成了生物序列比对、模式发现等数据处理的低效率。研究了生物序列数据的特征,分析并归纳了用户对生物序列数据的查询需求,提出了一个新的生物序列数据模型BioSeg。BioSeg模型由描述部分和多维数组组成,描述部分表示生物序列注释和其他相关信息,多维数组表示具体序列（如DNA序列“ATCCCGTA”）。BioSeg模型提供了实现生物序列数据查询的代数操作。相对于生物序列数据的文本存储方式,BioSeg模型提供的数据查询具有良好的效率和灵活性。     

DNA chips for species identification and biological phylogenies

The codeword design problem is an important problem in DNA computing and its applications. Several theoretical analyses as well as practical solutions for short oligonucleotides (up to 20-mers) have been generated recently. These solutions have, in turn, suggested new applications to DNA-based indexing and natural language processing, in addition to the obvious applications to the problems of reliability and scalability that generated them. Here we continue the exploration of this type of DNA-based indexing for biological applications and show that DNA noncrosshybridizing (nxh) sets can be successfully applied to infer ab initio phylogenetic trees by providing a way to measure distances among different genomes indexed by sets of short oligonucleotides selected so as to minimize crosshybridization. These phylogenies are solidly established and well accepted in biology. The new technique is much more effective in terms of signal-to-noise ratio, cost and time than current methods. Second, it is demonstrated that DNA indexing does provide novel and principled insights into the phylogenesis of organisms hitherto inaccessible by current methods, such as a prediction of the origin of the Salmonella plasmid 50 as being acquired horizontally, likely from some bacteria somewhat related to Yesinia. Finally, DNA indexing can be scaled up to newly available universal DNA chips readily available both in vitro and in silico. In particular, we show how a recently obtained such set of nxh 16-mers can be used as a universal coordinate system in DNA spaces to characterize very large groups (families, genera, and even phylla) of organisms on a uniform biomarker reference system, a veritable and comprehensive “Atlas of Life”, as it is or as it could be on earth.     

Methods for integration of heterogeneous information resources in molecular biology in the digital library GeneExpress

Difficulties in integrating information resources (IRs) in molecular biology are due to a complex hierarchical and/or network organization of data, to their heterogeneity, complex interrelations, insufficient formalization, and to incompleteness. To overcome these difficulties, a digital library called GeneExpress has been under development in the Institute of Cytology and Genetics of the Siberian Division of Russian Academy of Sciences. This system, which belongs to a new class of information systems, integrates a great number of data-bases and hundreds of computer programs designed for processing information on the structure and functions of DNA, RNA, and proteins. The foundation of our approach is provided by hypertext integration, integration on the basis of a unified object-oriented environment by mapping the data into a canonical model with the use of specially designed mediators, and semantic data integration. A prototype of an implementation of this approach used in the current version of GeneExpress is described.     

An improved microcomputer program for finding gene- or gene family-specific oligonucleotides suitable as primers for polymerase chain reactions or as probes.

We present here an easy-to-use computer program which finds oligonucleotides suitable as primers in polymerase chain reactions (PCR) or as probes for hybridization. In contrast to other programs used for this purpose, the additional advantage of this one is the possibility of directly detecting gene- as well as gene family-specific oligonucleotides. For this purpose, up to 200 different DNA sequences, of maximally 65,000 nucleotides each, can be scanned in a single search to ensure either single or multiple gene binding of the PCR primers or probes. Specific oligonucleotides for genes carrying internal repetitions and for single genes belonging to a set of highly conserved genes can also be detected. Many parameters such as exclusion of simple sequences, which are known to be highly repeated throughout various genomes or regions of stable secondary structures in both primer-primer and primer-template, can be taken into consideration and avoided. Furthermore, the G + C content and the length of the oligonucleotides can be changed in a broad range by the user.     

Multiplex SNP genotyping using Locked Nucleic Acid and microfluidics

Locked Nucleic Acid's or LNA are a new class of bicyclic DNA analogues that have a high affinity and specificity towards complementary nucleic acids. LNA containing oligonucleotides were used to develop a multiplex SNP genotyping assay based entirely on hybridization between capture probe and target. The approach incorporates a polymer microarray platform, photochemistry for immobilization of oligonucleotides onto microarrays, and a dedicated software tool to aid primer and capture probe design for highly multiplex genotyping. Furthermore, these technologies are combined in an integrated microfluidics platform for simple, highly multiplex and robust SNP genotyping.     

Privacy issues with DNA databases and retention of individuals' DNA information by law enforcement agencies: the holding of the European Court of Human Rights case S and Marper v. United Kingdom should be adapted to American Fourth Amendment jurisprudence

When law enforcement agencies collect, retain, and use individuals' DNA information in DNA databases for crime prevention purposes the presumption of innocence is reduced for those individuals. Collection and use of DNA information has benefits, greatly assisting law enforcement agencies in their criminal investigations. However, problems arise when DNA information is retained and used for individuals who have been acquitted, have had the charges pressed against them dropped, have been arrested for crimes short of violent or sexual felonies, or have served out the term of their sentence. While federal law has expungement provisions for individuals who are ultimately not convicted, state laws on expungement are often silent or inadequate. In order to prevent the presumption of innocence from being significantly eroded by the improper use of DNA information, US courts should adopt the test elaborated in the European Court of Human Rights case S and Marper v. UK, which may require law enforcement agencies to expunge their databases of DNA information of individuals depending on the individuals' statuses as arrestees, non-convicts, convicts, or ex-convicts, and in consideration of the severity of the offense alleged which provided the law enforcement rationale to extract the individuals' DNA. Adoption of the Marper test will allow US courts to balance the interests of the government in crime prevention and criminal investigation against the privacy interests of the individual citizen with a degree of far greater nuance than the sledgehammer alternative, namely, the universal DNA database proposed by Yale Law School Professor Akhil Amar and Paul Monteleoni.     

Anaesthesia record system on handheld computers--pilot experience and uses for quality control and clinical guidelines

This paper describes a mobile information system to collect patient information for anesthesia quality control. In this system, a mobile database program was designed for use on handheld computers (Pocket PC). This program is used to collect patient data at the bedside on the handhelds, with a daily synchronization of the data between the anaesthesiologists' handhelds with the anaesthesia database. All collected data are later used for quality control analysis. Furthermore, clinical guidelines will be included on these same handhelds. During the pilot phase, data from a sample set of about 300 patients were incorporated. The processes and interfaces of the system are presented in the paper. The current mobile database system has been designed to replace the original paper-based data collection system. The individual anaesthesiologist's handheld synchronizes patient data daily with anaesthesia database center. This information database is analyzed and used not only to give feedback to the individual doctor or center, but also to review the use of the guidelines provided and the results of their utilization.     

Dynamic arrays for fast, efficient, data manipulation during image analysis: a new software tool for exploratory data analysis.

Memory reallocation is used to construct a run-time data structure for fast/efficient storage of information during collection and analysis. The data structure presented uses dynamic memory but does not require the use of pointers to link nodes of information together. It allows for simple and efficient access to data via array indexing rather than through the use of lists or tree structures and it provides flexibility for competing storage requirements that are determined dynamically. The data structure is developed in the C programming language and a suite of ANSI standard C subroutines that make up a run-time data structure management system is provided.     

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.     

基于OPC的焦化厂备煤系统异构网络化控制系统设计

针对焦化厂备煤生产车间内部由于具有多种网络体系或者结构的现场总线及控制系统而造成信息无法共享的问题,提出了一种基于OPC技术的异构网络化控制系统的设计方案,详细介绍了系统的OPC服务器/客户端的设计开发。该系统通过基于工业以太网的TCP/IP体系连接所有子系统,并利用OPC技术为异构数据源提供统一数据接口,使数据管理层能够获取各种数据,解决了异构网络中数据信息转换、集成及存储问题,满足了企业生产过程中信息互操作以及与企业信息系统集成的要求。     

DNA 数据存储——机遇与挑战

自人类进入信息时代以来,全球信息总量飞速膨胀,为数据存储行业带来极大挑战。当前的信息存储工具存在许多缺陷,如信息密度低、使用寿命短、环境污染等,而脱氧核糖核酸(DNA)作为天然的遗传信息载体,具有信息密度高、稳定性高、保存时间长、维护成本低等优点,可能成为信息存储领域的卓越选择。尽管 DNA 存储目前面临读写成本高、速度慢、错误率高等挑战,但在某些领域也有着独特的优势,如“冷”数据存储和军事加密存储等。目前,DNA 存储的潜在发展方向主要包括在军事、航空航天等特殊场景下的应用,高容错的编解码方案,生物活体存储体系,脱离测序的信息读取方法,以及集成化的存储系统和统一行业标准等。希望在不久的将来,DNA 存储能够实现规模化应用,迎来数据存储的新纪元。     

Facile method to detect oligonucleotides with functionalized polydiacetylene vesicles

Polydiacetylene vesicles were used to detect oligonucleotides in the present paper. For this system, probe-oligonucleotide-functionalized polydiacetylene vesicles were used as indicators of color transition and amplification tags at the same time in the detection of oligonucleotides. The method described is simple, rapid, and suitable for detection of oligonucleotides by naked eye. The influences of dimyristoylphosphatidylcholine (DMPC) in the color changeable polydiacetylene vesicles on the detection of oligonucleotides were also studied. The experimental results demonstrated that DMPC can effectively adjust the mechanical stress of polydiacetylenic structure and the content of DMPC in polydiacetylene structure is a crucial factor for a more sensitive polydiacetylene-based sensor. The maximum colorimetric response for the detection of oligonucleotides was obtained for the polydiacetylene vesicle composed of TCDA/DMPC/probe-DNA with molar ratio of 0.60:0.39:0.01. Both cases for too much or for too less DMPC in polydiacetylene vesicles are not benefit to the detection for this system. The TEM images further confirmed the results obtained.     

基于纳米孔读取的 DNA 存储发展与展望

现代社会正处于数据爆炸的时代,全球对数据存储的需求已经远远超过了已有的存储能力。DNA 是一种天然的遗传信息载体,可实现稳定、高效、低功耗的数据存储。目前的 DNA 存储过程主要分为 6 个环节：编码、写入、保存、检索、读取、解码。纳米孔测序技术被广泛应用于读取 DNA 中所存储的信息。该文系统性地介绍了纳米孔分子检测技术的原理和发展历史,及其在 DNA 存储中的应用。此外,该文总结了机器学习在纳米孔检测技术中的应用,着重介绍了结合机器学习的新型纳米孔检测技术。该文为纳米孔检测技术的发展提供了新方向,也为新型实用化 DNA 存储系统的发展奠定了基础。     

Fuzzy logic with biomolecules

 The uncertain and inexact nature of the chemical reactions used to implement DNA computations can be turned into an advantage for implementing robust soft computing systems. The key feature of DNA hybridization that makes it appropriate for fuzzy computing is the uncertainty and incompleteness in the formation of a double-stranded duplex from single-stranded oligonucleotides. To implement fuzzy computing, a set of encoding DNA molecules is given that reproduces a specific membership function in the energetics of the DNA duplex. In addition, a fuzzy inference system implemented with DNA hybridization on solid supports is discussed. The ultimate success of this idea as a general technique, however, is dependent on the actual geometry of the Gibbs free-energy landscapes in the space of all duplex formations. Elucidating this problem is undoubtedly of great importance for biomolecular implementation of soft-computing because it may, in particular, shed light on the true import of fuzzy models in biological processes fundamental to life.     

Emerging applications of aptamers to micro- and nanoscale biosensing

Micro- and nanofabrication has allowed the production of ultra-sensitive, portable, and inexpensive biosensors. These devices generally rely on chemical or biological receptors which recognize a particular compound of interest and relay this recognition event effectively by transduction. Recent advances in RNA and DNA synthesis have enabled the use of aptamers, in vitro generated oligonucleotides, which offer high affinity biomolecular recognition to a theoretically limitless variety of analytes. DNA and RNA aptamers have gained so much attention in the biosensor community, that they have begun competing with more established affinity ligands including enzymes, lectins, and most notably, immunoreceptors such as antibodies. This article reviews the current state-of-the-art of aptasensors, or biosensors that use aptamers as molecular recognition elements, emphasizing the synergy between aptamer-based biosensing and micro- and nanotechnology. Aptasensors developed on micro- and nanoscale platforms based on mass changes, electroanalytical techniques, optical transduction, and purification and separation methods will be covered.     

多重空间映射与超结构查询

多重空间映射是将多个信息系统数据库中的事物组织成多层逻辑空间,通过映射快速地确定查询对象。超结构查询是通过“多重空间映射”的方法,实现超越应用系统结构的、快速、方便、广泛的信息查询的一种新技术。它不受功能系统的限制,不受数据库表结构的限制,能够在各个功能系统的多个数据库表中查找匹配的信息,可有效解决多个应用系统范围的数据查询,并使信息系统中的数据得到更充分的利用。     

非天然碱基基因密码扩展 DNA 数据存储的机遇与挑战

目前,传统的存储技术主要将硅基材料作为存储介质,但全球现有的硅资源却无法满足日益增长的数据存储需求。随着数据时代的发展,存储技术创新面临新的挑战。在自然界,DNA 分子储存着丰富的遗传信息。从化学生物学的角度分析,将 DNA 分子作为介质进行数据信息存储有望为存储技术的创新提供一个新机遇,而非天然碱基核苷酸可以扩充遗传字母表,增加 DNA 存储容量,但在其实际应用方面,目前还有很多问题待解决。该文综述了 DNA 存储技术的研究进展,对当前 DNA 存储现状、待解决的技术难题与发展前景等进行了分析;并在此基础上,介绍了非天然碱基对(UBPs)作为合成生物学的一个新方向在 DNA 信息存储领域的潜在优势和技术挑战。     

Designing information systems for nursing practice: data base and knowledge base requirements of different organizational technologies

One of the major causes of failure of information system design is the failure of developers to take into account the organizational environment, thereby leading to an unusable system. The first step in designing an effective system is to describe the user's view of the system, a view that incorporates how the system will help users to manage information in their particular organizational environment. For nurses involved in designing a nursing information system, a useful way of considering the organizational environment is provided by Perrow. The organizational technologies described by Perrow can be viewed as different models of nursing practice, each with particular requirements for a knowledge base and a data base. Nurses can identify the model that most closely corresponds to actual or desired nursing practice in their agencies and use the model's associated knowledge base and data base requirements as a guide to specifying the information system to be developed.