A Perl toolkit for LIMS development

Background  

High throughput laboratory techniques generate huge quantities of scientific data. Laboratory Information Management Systems (LIMS) are a necessary requirement, dealing with sample tracking, data storage and data reporting. Commercial LIMS solutions are available, but these can be both costly and overly complex for the task. The development of bespoke LIMS solutions offers a number of advantages, including the flexibility to fulfil all a laboratory's requirements at a fraction of the price of a commercial system. The programming language Perl is a perfect development solution for LIMS applications because of Perl's powerful but simple to use database and web interaction, it is also well known for enabling rapid application development and deployment, and boasts a very active and helpful developer community. The development of an in house LIMS from scratch however can take considerable time and resources, so programming tools that enable the rapid development of LIMS applications are essential but there are currently no LIMS development tools for Perl.     

A relational database of protein structures designed for flexible enquiries about conformation

A relational database of protein structure has been developed to enable rapid and flexible enquiries about the occurrence of many aspects of protein architecture. The coordinates of 294 proteins from the Brookhaven Data Bank have been processed by standard computer programs to generate many additional terms that quantify aspects of protein structure. These terms include solvent accessibility, main-chain and side-chain dihedral angles, and secondary structure. In a relational database, the information is stored in tables with columns holding the different terms and rows holding the different entries for the terms. The different relational base tables store the information about the protein coordinate set, the different chains in the protein, the amino acid residues and ligands, the atomic coordinates, the salt bridges, the hydrogen bonds, the disulphide bridges and the close tertiary contacts. The database was established under ORACLE management system. Enquiries are constructed in ORACLE using SQL (structured query language) which is simple to use and alleviates the need for extensive computer programs. A single table can be searched for entries that meet various criteria, e.g. all protein solved to better than a given resolution. The power of the database occurs when several tables, or the entries in a single table, are cross-correlated. For example the dihedral angles of proline in the fourth position in an alpha-helix in high resolution structures can be rapidly obtained. The structural database provides a powerful tool to obtain empirical rules about protein conformation. This database of protein structures is part of a joint project between Birkbeck College and Leeds University to establish an integrated data resource of protein sequences and structures (ISIS) that encodes the complex patterns of residues and coordinates that define protein conformation. The entire data resource (ISIS) will provide a system to guide all areas of protein modelling including structure prediction, site-directed mutagenesis and de novo protein design. The availability of ISIS is described in the paper.     

Fluid shear stress modulates endothelial inflammation by targeting LIMS2

Mechanosensitive genes regulate multiple cardiovascular pathophysiological processes and disorders; however, the role of flow-sensitive genes in atherosclerosis is still unknown. In this study, we identify LIM Zinc Finger Domain Containing 2 (LIMS2) that acts as a mechanosensitive gene downregulated by disturbed flow (d-flow) both in human endothelial cells (ECs) in vitro and in mice in vivo. Mechanistically, d-flow suppresses LIMS2 expression, which leads to endothelial inflammation by upregulating typical inflammatory factors, VCAM-1, and ICAM-1 in human ECs. The findings indicate that LIMS2, the new flow-sensitive gene, may help us to find a new insight to explain how d-flow caused endothelial inflammation and provide a new therapeutic approach for atherosclerosis in the future.     

Free molecular biological software available from the EMBL file server

A new service provided by EMBL (EMBL Softsvare File Server)is described that will make free molecular biology softwareavailable to anyone with computer network access. MS–DOS,Apple Macintosh and VAX/VMX are supported at the moment. Theprograms will be delivered by normal electronic mail; conversionmechanisms will transfor binary files to ASCII to allow mailtransfer. This service will also help authors to distributetheir software conveniently.     

Integrating mass spectrometry data systems from different manufacturers in a local area network

Several scientific instruments suppliers are offering complete networking and automation packages for analytical laboratories. Nevertheless there is still considerable work to be done in the area of standardization of file formats generated by different data acquisition systems supplied by scientific instruments manufacturers. Recent work on the netCDF transfer protocol for mass spectrometry data suggests that good progress is being made in the area of data formats.Our laboratory operates a number of diverse instruments, including two high resolution systems (ZAB 2F, 70 SEQ) and one quadrupole (QMD 1000) from Fisons Instruments, one ion trap system from Finnigan (ITS 40) and one pyrolysis mass spectrometer from Horizon Instruments (RAPyD-400), all equipped with autosamplers. This instruments are physically located in two distinct laboratories. The data systems are based on very different computers, including a DEC PDP-11/24, a VAX 4000/90 and several PCs.The large amount of data produced by the MS laboratory and the implementation of GLPs, (Good Laboratory Practices) and GALPs (Good Automated Laboratory Practices) prompted us to examine the possibility of networking the instrumentation in a client/server computing environment. All instrument data systems have been connected to the institute network via ethernet, using either DECnet or TCP/IP. A VAXCluster consisting in a VAXStation 4000/90 host and a VAXStation 3100 satellite has been configured as a server using DEC PATHWORKS V.4.1 server software. This allows for file, disk, application and print services to all the PC clients connected network wide. Unattended distributed backup and restore services for PC hard disks are implemented. Mass spectrometry data files are permanently archived in their original format on 4 Gbyte tape cartridges and stored for later retrieval. Files can be transferred to any office PC running the appropriate mass spectrometry software. A centralized spectra and structure information management system based on the MassLib (Chemical Concepts) software allows for library searches using the SISCOM algorithm after specific file conversion programs or using JCAMP-DX files. Furthermore, the mass spectrometer data systems are readied for their eventual incorporation into a LIMS.     

ISPyB: an information management system for synchrotron macromolecular crystallography

MOTIVATION: Individual research groups now analyze thousands of samples per year at synchrotron macromolecular crystallography (MX) resources. The efficient management of experimental data is thus essential if the best possible experiments are to be performed and the best possible data used in downstream processes in structure determination pipelines. Information System for Protein crystallography Beamlines (ISPyB), a Laboratory Information Management System (LIMS) with an underlying data model allowing for the integration of analyses down-stream of the data collection experiment was developed to facilitate such data management. RESULTS: ISPyB is now a multisite, generic LIMS for synchrotron-based MX experiments. Its initial functionality has been enhanced to include improved sample tracking and reporting of experimental protocols, the direct ranking of the diffraction characteristics of individual samples and the archiving of raw data and results from ancillary experiments and post-experiment data processing protocols. This latter feature paves the way for ISPyB to play a central role in future macromolecular structure solution pipelines and validates the application of the approach used in ISPyB to other experimental techniques, such as biological solution Small Angle X-ray Scattering and spectroscopy, which have similar sample tracking and data handling requirements.     

Calculation of immobilized enzyme reaction progress curves from nested ordered-sequential rate expressions

A method for estimating immobilized enzyme reaction progress curves, using simultaneous non-linear regression analysis of 2–3 substrate concentrations with time, is presented. These facile procedures involve using nested Gauss–Newton curve fitting algorithms on a Microsoft EXCEL spreadsheet. We refer to our technique as "nested" because the analysis consists of two or three mutually parameter-dependent sets of computations associated with bi- or termolecular enzyme-catalyzed reactions, respectively. We have applied the method to immobilized glucose oxidase-catalyzed reactions ([ -glucose] and [O₂] with time) and found that the kinetic parameters from initial velocity data were similar to those determined by the nested curve fitting method discussed herein.     

LIMS in the manufacturing environment

The type of laboratory that implements a LIMS is very important in determining the requirements of the LIMS. This article focuses on the requirements for a manufacturing LIMS. The objectives of a manufacturing laboratory that a LIMS should support are presented. Issues that should be considered in the initial planning stage of implementing a manufacturing LIMS are discussed. Functional requirements for a manufacturing LIMS examined in the article are the ability to: (1) handle various material types, (2) grade products, (3) allow flexibility in test method configuration, (4) handle data limits and variable sets of data. (5) revise and track test methods and specifications, and (6) maintain a customer and/or supplier database.     

Program MULDER -- a tool for extracting torsion angles from NMR data

MULDER (Mostly UniversaL Dihedral angle ExtractoR) is a program for extraction of torsion angle information from NMR data. Currently, it can analyze two types of input data: The torsion angle data, where several ³J-coupling constants and/or interatomic distances are combined in order to reduce the torsion angle ambiguity arising from solving the isolated Karplus (or distance) equation, and the sugar pucker data, where the dynamics of five-membered sugar rings is evaluated by postprocessing the results calculated from ³J_(HH) coupling constants by program PSEUROT. Program MULDER can be used either as an alternative to r-MD programs in situations where only specific structural features are studied, or as a preparatory tool in connection with full r-MD structure calculation for extraction of unambiguous torsion angle restraints.     

Screening protein and nucleic acid sequences against libraries of patterns.

We describe programs that can screen nucleic acid and protein sequences against libraries of motifs and patterns. Such comparisons are likely to play an important role in interpreting the function of sequences determined during large scale sequencing projects. In addition we report programs for converting the Prosite protein motif library into a form that is compatible with our searching programs. The programs work on VAX and SUN computers.     

GENEUS, a computer system for DNA and protein sequence analysis containing an information retrieval system for the EMBL data library.

We describe a comprehensive computer system, GENEUS, for extensive DNA, RNA and protein sequence analysis. The analysis system is developed for the DEC VAX/VMS computer and uses the EMBL Nucleic Acid Sequence Data Library. Help information is available on-line on terminal screen. To speed up system handling, a qualifier oriented user communication is employed. All results are stored on files making them accessible to the computer editor. An information retrieval system for the EMBL Nucleotide Sequence Data Library is also described. A defined data-base interface allows connection to other analysis programs.+     

黑龙江省野生东北虎调查管理信息系统的构建

文章以黑龙江省野生东北虎（Panthera tigris altaica）野外调查数据为基础,利用地理信息系统技术、计算机技术与野生动物资源调查管理技术,构建了黑龙江省野生东北虎调查管理信息系统。主要运用面向对象程序设计语言C#和ArcGIS Engine嵌入式组件技术以及SQL Server数据库技术,设计并构建东北虎调查管理系统,实现了对野生东北虎调查数据的图形可视化操作管理。同时,结合研究区域内的自然因素和人文因素对调查资源进行动态的空间分析,及时准确地反映出东北虎的种群数量和空间变化规律,并制作出相应的分类专题图及野外分布信息统计图表等。该管理信息系统将有助于野生东北虎种群及栖息地调查数据与资料的科学管理,对于推动我国野生东北虎就地保护和科学管理具有重要意义。     

Electronic spreadsheet program for estimating two-compartment intravenous pharmacokinetic parameters by least squares linear regression analysis

A microcomputer program using an electronic spreadsheet program was developed to calculate pharmacokinetic values of thiacetarsamide sodium, a drug used to kill the adult heartworm (Dirofilaria immitis) parasite of the dog. A least squares, semilogarithmic regression analysis was done on data using a two compartment intravenous model. The data entered includes the time after injection and the drug concentration at that time. A graph of the points can be viewed or plotted, with the time on the x-axis, and the natural log of the drug concentration on the y-axis.The program was developed on a Televideo (512 kbytes) microcomputers⁷. The spreadsheet used was Lotus 123⁷¹     

medplot: A Web Application for Dynamic Summary and Analysis of Longitudinal Medical Data Based on R

In biomedical studies the patients are often evaluated numerous times and a large number of variables are recorded at each time-point. Data entry and manipulation of longitudinal data can be performed using spreadsheet programs, which usually include some data plotting and analysis capabilities and are straightforward to use, but are not designed for the analyses of complex longitudinal data. Specialized statistical software offers more flexibility and capabilities, but first time users with biomedical background often find its use difficult. We developed medplot, an interactive web application that simplifies the exploration and analysis of longitudinal data. The application can be used to summarize, visualize and analyze data by researchers that are not familiar with statistical programs and whose knowledge of statistics is limited. The summary tools produce publication-ready tables and graphs. The analysis tools include features that are seldom available in spreadsheet software, such as correction for multiple testing, repeated measurement analyses and flexible non-linear modeling of the association of the numerical variables with the outcome. medplot is freely available and open source, it has an intuitive graphical user interface (GUI), it is accessible via the Internet and can be used within a web browser, without the need for installing and maintaining programs locally on the user’s computer. This paper describes the application and gives detailed examples describing how to use the application on real data from a clinical study including patients with early Lyme borreliosis.     

生物实验信息管理模块建模技术研究

实验信息管理模块是生物实验室信息管理系统的核心,其设计的好坏直接关系到整个系统建设的成败。针对生物实验室实验流程灵活,数据流网络复杂等特点,研究设计了一套实验信息管理模块的模型,并将研究的模型用于基因测序实验室信息管理系统的开发并取得了成功。实践证明,该模型为实验室信息系统(LIMS)中实验管理模块的开发提供了理论支撑,并且提高了LIMS的开发效率。     

smogd: software for the measurement of genetic diversity

Software for the measurement of genetic diversity (SMOGD) is a web-based application for the calculation of the recently proposed genetic diversity indices G'(ST) and D(est) . SMOGD includes bootstrapping functionality for estimating the variance, standard error and confidence intervals of estimated parameters, and SMOGD also generates genetic distance matrices from pairwise comparisons between populations. SMOGD accepts standard, multilocus Genepop and Arlequin formatted input files and produces HTML and tab-delimited output. This allows easy data submission, quick visualization, and rapid import of results into spreadsheet or database programs.     

江苏植物资源信息系统

江苏植物资源信息系统是用微软公司的Visual Basic(6.0)在Windows ME环境下开发完成的。首先将数据输入Ms Excel 2000,然后输出到Ms Access 97以便调用。本数据库共收录江苏分布的植物2205种、334变种、21栽培变种和1534异名。系统采用ODBC(Open Database Connectivity)和Jet(Joint Engine Technology)接口连接数据库,SQL(Structure Query Language)进行检索查询。本系统能够任意查询江苏省所有植物的中文名、拉丁名、所属科名、属名;并能显示植物种的形态特征、地理分布、生境、经济意义以及图片。该系统能在中文Windows 95,Windows 98和Windows ME环境下运行。