Ultra-Structure database design methodology for managing systems biology data and analyses

Background  

Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping).     

Utility and features of a customized PC Windows-based relational database for managing microbial strain data

In addition to storing microbes, culture collections in industry, government or universities manage a vast and continuously expanding library of information on strain history and properties. An efficient and cost-effective computer database system is required for entering, analyzing and searching these data. This report describes the utility and features of a comprehensive database which consists of a commercially available relational database system combined with customized screens for data entry, viewing and report generation. The application was developed using Microsoft Access and Visual Basic to operate in the Windows environment on a local area network. Received 18 June 1997/ Accepted in revised form 21 November 1997     

ParaSiteDB – A user-friendly database for managing a parasitological collection

ParaSiteDB is an application for arranging and managing a parasitological collection. It has been designed to provide a user-friendly, easily manageable and searchable site and is suitable for small to bigger collections.The source code of the application is available on GitHub: https://github.com/goobar4/aacrg.The demonstration version of the application is available on https://syrota.info/wormbasehttp://syrota.info/wormbase.     

Focus gradient correction applied to tilt series image data used in electron tomography

The resolution in 3D reconstructions from tilt series is limited to the information below the first zero of the contrast transfer function unless the signal is corrected computationally. The restoration is usually based on the assumption of a linear space-invariant system and a linear relationship between object mass density and observed image contrast. The space-invariant model is no longer valid when applied to tilted micrographs because the defocus varies in a direction perpendicular to the tilt axis and with it the shape of the associated point spread function. In this paper, a method is presented for determining the defocus gradient in thin specimens such as sections and 2D crystals, and for restoration of the images subsequently used for 3D reconstruction. The alignment procedure for 3D reconstruction includes area matching and tilt geometry refinement. A map with limited resolution computed from uncorrected micrographs is compared to a volume computed from corrected micrographs with extended resolution.     

BIOS a database for marine biological data

BIOS is a computerised database system for holding species distributiondata. Emphasis has been placed on the flexibility in which storedinformation can be accessed. Multiple retrieval pathways permitsimple enquiries to be answered or complicated interrogationsequences for statistical treatment of data. The structuralorganisation of the database is explained and details of itscontents are listed. Examples of applications in the fieldsof zoogeography and ecology are given together with illustrations.     

DRESS: a database of REfined solution NMR structures

Several studies have shown that biomolecular NMR structures are often of lower quality when compared to crystal structures, and consequently they are often excluded from structural analyses. We present a publicly available database of re-refined NMR structures, exhibiting significantly improved quality. This database (available at http://www.cmbi.kun.nl/dress/) presents a uniformly refined and validated set of structural models that improves the value of these NMR structures as input for experimental and theoretical studies in many fields of research.     

Web portal to an image database for high-resolution three-dimensional reconstruction

The exponential increase of image data in high-resolution reconstructions by electron cryomicroscopy (cryoEM) has posed a need for efficient data management solutions in addition to powerful data processing procedures. Although relational databases and web portals are commonly used to manage sequences and structures in biological research, their application in cryoEM has been limited due to the complexity in accomplishing the dual tasks of interacting with proprietary software and simultaneously providing data access to users without database knowledge. Here, we report our results in developing web portal to SQL image databases used by the Image Management and Icosahedral Reconstruction System (IMIRS) to manage cryoEM images for subnanometer-resolution reconstructions. Fundamental issues related to the design and deployment of web portals to image databases are described. A web browser-based user interface was designed to accomplish data reporting and other database-related services, including user authentication, data entry, graph-based data mining, and various query and reporting tasks with interactive image manipulation capabilities. With an integrated web portal, IMIRS represents the first cryoEM application that incorporates both web-based data reporting tools and a complete set of data processing modules. Our examples should thus provide general guidelines applicable to other cryoEM technology development efforts.     

On the classification of a small imbalanced cytogenetic image database

Solving a multiclass classification task using a small imbalanced database of patterns of high dimension is difficult due to the curse-of-dimensionality and the bias of the training toward the majority classes. Such a problem has arisen while diagnosing genetic abnormalities by classifying a small database of fluorescence in situ hybridization signals of types having different frequencies of occurrence. We propose and experimentally study using the cytogenetic domain two solutions to the problem. The first is hierarchical decomposition of the classification task, where each hierarchy level is designed to tackle a simpler problem which is represented by classes that are approximately balanced. The second solution is balancing the data by up-sampling the minority classes accompanied by dimensionality reduction. Implemented by the naive Bayesian classifier or the multilayer perceptron neural network, both solutions have diminished the problem and contributed to accuracy improvement. In addition, the experiments suggest that coping with the smallness of the data is more beneficial than dealing with its imbalance     

Standardizing cancer biomarkers criteria: data elements as a foundation for a database. Inflammatory mediator/M-CSF as model marker

The purpose of this position article was to design a set of criteria (data elements) for a wide range of cancer biomarkers (CBs) in an attempt to standardize biomarkers features through a common language as a foundation for a database. Data elements are described as a set of generic criteria, which should characterize nearly all biomarkers introduced in the literature. Data elements were extracted from the review of prominent features that biomarkers represent within various categories. The extracted characteristics of biomarkers produced a short list of shared and unique generic features such as biological nature and history; stage/phase of study; sensitivity and specificity; modes of action; risk assessment; validation status; technology, and recommendation status for diversified biomarkers. To tailor data elements on specific markers, a cytokine, such as macrophage-colony stimulating factor (M-CSF), which has been proposed as a ‹potentially suitable biomarker’ for diagnosis of ovarian, lung, breast, pancreatic, and colorectal cancers, was selected as a Model biomarker. Small scale clinical studies suggested the superior usefulness of M-CSF compared with traditional markers for cancer detection. A key criterion for selecting Model marker and tailoring data elements for detection of cancer was the comparison of data on its specificity and sensitivity with traditional markers. The design of data elements for standardizing CBs criteria is considered a Research Tool and a foundation for developing a comprehensive CBs database useful for oncology researchers for a wide range of biomarkers. Validation, integration and proper packaging, data visualization and recommendation of suitability of CBs, by a panel of experts, for technology development are important challenging next steps toward developing a reliable database, which would allow professionals to effectively retrieve and study integrated information on potentially useful markers; identify important knowledge gaps and limitations of data; and assess state of technologies and commercialization of markers at a point of need. Appropriate use of integrated information on biomarkers in clinical practices would eventually account for more cost-effective characteristics of an individual’s state of health.     

Folding elastic transmembrane helices to fit in a low-resolution image by electron microscopy

Structure prediction of membrane proteins could be constrained and thereby improved by introducing data of the observed molecular shape. We studied a coarse-grained molecular model that relied on residue-based dummy atoms to fold the transmembrane helices of a protein in the observed molecular shape. Based on the inter-residue potential, the α-helices were folded to contact each other in a simulated annealing protocol to search optimized conformation. Fitting the model into a three-dimensional volume was tested for proteins with known structures and resulted in a fairly reasonable arrangement of helices. In addition, the constraint to the packing transmembrane helix with the two-dimensional region was tested and found to work as a very similar folding guide. The obtained models nicely represented α-helices with the desired slight bend. Our structure prediction method for membrane proteins well demonstrated reasonable folding results using a low-resolution structural constraint introduced from recent cell-surface imaging techniques.     

The cell centered database project: an update on building community resources for managing and sharing 3D imaging data

Databases have become integral parts of data management, dissemination, and mining in biology. At the Second Annual Conference on Electron Tomography, held in Amsterdam in 2001, we proposed that electron tomography data should be shared in a manner analogous to structural data at the protein and sequence scales. At that time, we outlined our progress in creating a database to bring together cell level imaging data across scales, The Cell Centered Database (CCDB). The CCDB was formally launched in 2002 as an on-line repository of high-resolution 3D light and electron microscopic reconstructions of cells and subcellular structures. It contains 2D, 3D, and 4D structural and protein distribution information from confocal, multiphoton, and electron microscopy, including correlated light and electron microscopy. Many of the data sets are derived from electron tomography of cells and tissues. In the 5 years since its debut, we have moved the CCDB from a prototype to a stable resource and expanded the scope of the project to include data management and knowledge engineering. Here, we provide an update on the CCDB and how it is used by the scientific community. We also describe our work in developing additional knowledge tools, e.g., ontologies, for annotation and query of electron microscopic data.     

The transfer of selected image data to a computer using a conductive tablet

The processing and analysis of images in a computer often requires the selection of particular features of a complex image for more detailed study. Sometimes such decisions are empirical, in which case it would be extremely difficult to describe a rigorous algorithm for detecting these features automatically in a computer. In this situation graphic tablets can be very useful as they allow an operator to use experience in deciding which features are to be transferred into a computer.A tablet is described which uses a conductive glass plate and pencil probe. A number of subroutines are available in a general purpose program for conventional processing, calculation and displays to be effected by simple option selection on the tablet. For specific applications in cell growth, modelling and three dimensional reconstruction of serial sections, special programs were developed which could include appropriate subroutines. The categorisation of subsections by an operator was particularly useful in allowing different methods of analysis and display to be applied to each. For example they could be displayed separately or given different density levels by choosing the appropriate option in the program.     

Phytochemical profiling as a solution to palliate disinfectant limitations

The indiscriminate use of biocides for general disinfection has contributed to the increased incidence of antimicrobial tolerant microorganisms. This study aims to assess the potential of seven phytochemicals (tyrosol, caffeic acid, ferulic acid, cinnamaldehyde, coumaric acid, cinnamic acid and eugenol) in the control of planktonic and sessile cells of Staphylococcus aureus and Escherichia coli. Cinnamaldehyde and eugenol showed antimicrobial properties, minimum inhibitory concentrations of 3–5 and 5–12 mM and minimum bactericidal concentrations of 10–12 and 10–14 mM against S. aureus and E. coli, respectively. Cinnamic acid was able to completely control adhered bacteria with effects comparable to peracetic acid and sodium hypochlorite and it was more effective than hydrogen peroxide (all at 10 mM). This phytochemical caused significant changes in bacterial membrane hydrophilicity. The observed effectiveness of phytochemicals makes them interesting alternatives and/or complementary products to commonly used biocidal products. Cinnamic acid is of particular interest for the control of sessile cells.