A web application to manage a database for liquid nitrogen tanks

Summary We have developed a software, Cell Database, for archiving records about cells stored in liquid nitrogen tanks. Once installed on a web server, the database is accessed through a standard web browser. This user-friendly and self-explanatory application is independent of computer platform and periodic upgrades of a commercial software. Our web application allows import of data from other database programs and adaptation to different tank formats, types of samples, and archiving needs.     

Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action

Successful drug discovery requires accurate decision making in order to advance the best candidates from initial lead identification to final approval. Chemogenomics, the use of genomic tools in pharmacology and toxicology, offers a promising enhancement to traditional methods of target identification/validation, lead identification, efficacy evaluation, and toxicity assessment. To realize the value of chemogenomics information, a contextual database is needed to relate the physiological outcomes induced by diverse compounds to the gene expression patterns measured in the same animals. Massively parallel gene expression characterization coupled with traditional assessments of drug candidates provides additional, important mechanistic information, and therefore a means to increase the accuracy of critical decisions. A large-scale chemogenomics database developed from in vivo treated rats provides the context and supporting data to enhance and accelerate accurate interpretation of mechanisms of toxicity and pharmacology of chemicals and drugs. To date, approximately 600 different compounds, including more than 400 FDA approved drugs, 60 drugs approved in Europe and Japan, 25 withdrawn drugs, and 100 toxicants, have been profiled in up to 7 different tissues of rats (representing over 3200 different drug-dose-time-tissue combinations). Accomplishing this task required evaluating and improving a number of in vivo and microarray protocols, including over 80 rigorous quality control steps. The utility of pairing clinical pathology assessments with gene expression data is illustrated using three anti-neoplastic drugs: carmustine, methotrexate, and thioguanine, which had similar effects on the blood compartment, but diverse effects on hepatotoxicity. We will demonstrate that gene expression events monitored in the liver can be used to predict pathological events occurring in that tissue as well as in hematopoietic tissues.     

Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource

Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol—SHIRPA. Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map of the mouse and assisting with the identification of genes underlying novel mutations—with consequent benefits for the analysis of gene function and the identification of novel pathways. Received: 16 December 1999 / Accepted: 16 December 1999     

基于Web的基因组序列数据库管理系统的设计与实现

设计一种基于网络的可用来存储和注释海量DNA数据的数据库模型。整个过程分为三部分：首先是构建数据库框架,然后对原始基因组序列数据进行批量注释并输出有效格式导入数据库,最后通过一个友好的用户交互界面,实现对基因组数据的在线读取,查询,注释等操作。设计的数据库用于解决大量产生并有待分析的基因组序列的有效存储和管理问题。     

Laboratory database to manage electrophoresis and chromatography separations and the associated samples

A database was developed to store, organize, and retrieve the data associated with electrophoresis and chromatography separations. It allows laboratories to store extensive data on separation techniques (analytical and preparative). The data for gel electrophoresis includes gel composition, staining methods, electric fields, analysis, and samples loaded. The database stores data on chromatography conditions, the samples used, and the fractions collected. The data structure of this database was designed to maintain the link between samples (including fractions) from chromatography separations and their analysis by gel electrophoresis. The database will allow laboratories to organize and maintain a large amount of separation and sample data in a uniform data environment. It will facilitate the retrieval of the separation history of important samples and the separation conditions used.     

Biological database design and implementation

We present our experience of building biological databases. Such databases have most aspects in common with other complex databases in other fields. We do not believe that biological data are that different from complex data in other fields. Our experience has led us to emphasise simplicity and conservative technology choices when building these databases. This is a short paper of advice that we hope is useful to people designing their own biological database.     

Development of a hollow-fiber system for large-scale culture of mammalian cells

A flat-bed hollow-fiber cell culture system has been developed which maximizes the utilization of the large fiber surface while diminishing significantly the problems inherent in a cartridge-type reactor. The reactor core consists of a shallow bed of hollow fibers sandwiched between two stainless-steel microporous filter plates through which the media flow is directed normal to the plane of the fiber bed. Reactors with both 930 and 9300 cm² of fiber surface have been successfully constructed and operated. A variety of cells has been grown in these reactors including SV3T3 cells, baby hamster kidney cells, Vero cells, and rhesus money kidney cells, and cell products such as plasminogen activator and migration inhibition factor (MIF) were produced. This system offers an excellent prototype for scaleup design.     

Development and implementation of a reduced risk peach arthropod management program in New Jersey

We implemented a 2-yr program to reduce organophosphorus and carbamate insecticide use and mitigate their associated risks as they relate to peach production in New Jersey and elsewhere. The main thrust integrated mating disruption with ground cover management practices to reduce oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Heteroptera: Miridae), abundance and damage. This Reduced Risk Peach Arthropod Management Program was compared with adjacent conventionally managed peach orchards. In 1999, we found 2.3 times fewer L. lineolaris and stink bugs (Euschistus servus (Say), E. tristigmus (Say), Acrostemum hilare (Say) (Heteroptera: Pentatomidae) and 2.0 times less heteropteran damaged peaches in reduced-risk orchards when compared with conventionally managed orchards. In 2000, we observed 4.9 times fewer heteropteran insects in reduced-risk orchards but damage levels were not significantly different between the two programs. In both years, G. molesta mating disruption gave at least 4 mo of noninsecticidal control of this major pest. The reduced-risk program provided a level of pest control that was equal to or better than conventional peach pest management programs while using fewer organophosporus and carbamate insecticides.     

Modeling the mouse lymphoma forward mutational assay: the Gene-Tox program database

An SAR model of the induction of mutations at the tk(+/-) locus of L5178Y mouse lymphoma cells (MLA, for mouse lymphoma assay) was derived based upon a re-evaluation of experimental results reported by a Gene-Tox (GT) working group [A.D. Mitchell, A.E. Auletta, D. Clive, P.E. Kirby, M.M. Moore, B.C. Myhr, The L5178Y/tk(+/-) mouse lymphoma specific gene and chromosomal mutation assay. A phase III report of the U.S. Environmental Protection Agency Gene-Tox Program, Mutation Res. 394 (1997) 177-303.]. The predictive performance of the GT MLA SAR model was similar to that of a Salmonella mutagenicity model containing the same number of chemicals. However, the structural determinants (biophores) derived from the GT MLA SAR model include both electrophilic as well as non-electrophilic moieties, suggesting that the induction of mutations in the MLA may occur by both direct interaction with DNA and by non-DNA-related mechanisms. This was confirmed by the observation that the set of biophores associated with MLA overlapped significantly with those associated with phenomena related to loss of heterozygosity, chromosomal rearrangements and aneuploidy. The MLA SAR model derived from the GT data evaluation was significantly more predictive than an SAR model previously derived from MLA data reported by the US National Toxicology Program [B. Henry, S.G. Grant, G. Klopman, H.S. Rosenkranz, Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms, Mutation Res. 397 (1998) 331-335.]. Moreover, the latter model appeared to be more complex than the former, suggesting that the GT induction data was both simpler mechanistically and more homogeneous than that of the NTP.     

GASdb: a large-scale and comparative exploration database of glycosyl hydrolysis systems

Background  

The genomes of numerous cellulolytic organisms have been recently sequenced or in the pipeline of being sequenced. Analyses of these genomes as well as the recently sequenced metagenomes in a systematic manner could possibly lead to discoveries of novel biomass-degradation systems in nature.     

An ENU-mutagenesis screen in the mouse: identification of novel developmental gene functions

Background

Mutagenesis screens in the mouse have been proven useful for the identification of novel gene functions and generation of interesting mutant alleles. Here we describe a phenotype-based screen for recessive mutations affecting embryonic development.

Methodology/Principal Findings

Mice were mutagenized with N-ethyl-N-nitrosurea (ENU) and following incrossing the offspring, embryos were analyzed at embryonic day 10.5. Mutant phenotypes that arose in our screen include cardiac and nuchal edema, neural tube defects, situs inversus of the heart, posterior truncation and the absence of limbs and lungs. We isolated amongst others novel mutant alleles for Dll1, Ptprb, Plexin-B2, Fgf10, Wnt3a, Ncx1, Scrib(Scrib, Scribbled homolog [Drosophila]) and Sec24b. We found both nonsense alleles leading to severe protein truncations and mutants with single-amino acid substitutions that are informative at a molecular level. Novel findings include an ectopic neural tube in our Dll1 mutant and lung defects in the planar cell polarity mutants for Sec24b and Scrib.

Conclusions/Significance

Using a forward genetics approach, we have generated a number of novel mutant alleles that are linked to disturbed morphogenesis during development.     

An efficient medical database system implementation with its tool and data structure consideration

The development of a new system for medical database application running on minicomputer under MUMPS system is described. Two kinds of data representation in global structure are briefly reviewed. The use of a subject oriented multi-dimensional data structure greatly simplifies database design and facilitates data manipulation, organization, selective retrieval and software development. It is concluded that the program generator approach can provide the flexibility necessary for various applications and future growth of computerized medical record system. The final system has been proven effective in practical operation. The future extension concerns the introduction of multi-microprocessor structure and logic representation is presented.     

Design and implementation of a mosquito database through an entomological ontology

There have been constant changes in the biology and behavior of the vector and parasite involved in the transmission of malaria. There is limited interest in developing new technologies and procedures for controlling the underlying factors of this threat, which poses an enormous challenge to health systems. To understand the various vector species and their interrelations is of prime importance in understanding the transmission mechanisms of malaria in order to react efficiently. To attain this objective, we have used an ontological approach to producing a database that we consider to be our own contribution in helping to control malaria vectors if eradication has been unsuccessful in the previous control campaign.     

Design and implementation of a mosquito database through an entomological ontology

There have been constant changes in the biology and behavior of the vector and parasite involved in the transmission of malaria. There is limited interest in developing new technologies and procedures for controlling the underlying factors of this threat, which poses an enormous challenge to health systems. To understand the various vector species and their interrelations is of prime importance in understanding the transmission mechanisms of malaria in order to react efficiently. To attain this objective, we have used an ontological approach to produce a database that we consider to be our own contribution in helping to control malarial vectors if eradication has been unsuccessful in the previous control campaign.     

Chloroplast 2010: a database for large-scale phenotypic screening of Arabidopsis mutants

Large-scale phenotypic screening presents challenges and opportunities not encountered in typical forward or reverse genetics projects. We describe a modular database and laboratory information management system that was implemented in support of the Chloroplast 2010 Project, an Arabidopsis (Arabidopsis thaliana) reverse genetics phenotypic screen of more than 5,000 mutants (http://bioinfo.bch.msu.edu/2010_LIMS; www.plastid.msu.edu). The software and laboratory work environment were designed to minimize operator error and detect systematic process errors. The database uses Ruby on Rails and Flash technologies to present complex quantitative and qualitative data and pedigree information in a flexible user interface. Examples are presented where the database was used to find opportunities for process changes that improved data quality. We also describe the use of the data-analysis tools to discover mutants defective in enzymes of leucine catabolism (heteromeric mitochondrial 3-methylcrotonyl-coenzyme A carboxylase [At1g03090 and At4g34030] and putative hydroxymethylglutaryl-coenzyme A lyase [At2g26800]) based upon a syndrome of pleiotropic seed amino acid phenotypes that resembles previously described isovaleryl coenzyme A dehydrogenase (At3g45300) mutants. In vitro assay results support the computational annotation of At2g26800 as hydroxymethylglutaryl-coenzyme A lyase.