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Network-based real-time radiation monitoring system in Synchrotron Radiation Research Center.

The real-time radiation monitoring system (RMS) in the Synchrotron Radiation Research Center (SRRC) has been upgraded significantly during the past years. The new framework of the RMS is built on the popular network technology, including Ethernet hardware connections and Web-based software interfaces. It features virtually no distance limitations, flexible and scalable equipment connections, faster response time, remote diagnosis, easy maintenance, as well as many graphic user interface software tools. This paper briefly describes the radiation environment in SRRC and presents the system configuration, basic functions, and some operational results of this real-time RMS. Besides the control of radiation exposures, it has been demonstrated that a variety of valuable information or correlations could be extracted from the measured radiation levels delivered by the RMS, including the changes of operating conditions, beam loss pattern, radiation skyshine, and so on. The real-time RMS can be conveniently accessed either using the dedicated client program or World Wide Web interface. The address of the Web site is http:// www-rms.srrc.gov.tw.

Computer Communication Networks↗

Calculation of residence times and radiation doses using the standard PC software Excel.

We developed a program which aims to facilitate the calculation of radiation doses to single organs and the whole body. IMEDOSE uses Excel to include calculations, graphical displays, and interactions with the user in a single general-purpose PC software tool. To start the procedure the input data are copied into a spreadsheet. They must represent percentage uptake values of several organs derived from measurements in animals or humans. To extrapolate these data up to seven half-lives of the radionuclide, fitting to one or two exponentional functions is included and can be checked by the user. By means of the approximate time-activity information the cumulated activity or residence times are calculated. Finally these data are combined with the absorbed fraction doses (S-values) given by MIRD pamphlet No. 11 to yield radiation doses, the effective dose equivalent and the effective dose. These results are presented in a final table. Interactions are realized with push-buttons and drop-down menus. Calculations use the Visual Basic tool of Excel. In order to test our program, biodistribution data of fluorine-18 fluorodeoxyglucose were taken from the literature (Meija et al., J Nucl Med 1991; 32:699-706). For a 70-kg adult the resulting radiation doses of all target organs listed in MIRD 11 were different from the ICRP 53 values by 1%+/-18% on the average. When the residence times were introduced into MIRDOSE3 (Stabin, J Nucl Med 1996; 37:538-546) the mean difference between our results and those of MIRDOSE3 was -3%+/-6%. Both outcomes indicate the validity of the present approach.

Adult↗

Combined use of sequence similarity and codon bias for coding region identification.

A computer program called BLASTX was previously shown to be effective in identifying and assigning putative function to likely protein coding regions by detecting significant similarity between a conceptually translated nucleotide query sequence and members of a protein sequence database. We present and assess the sensitivity of a new option to this software tool, herein called BLASTC, which employs information obtained from biases in codon utilization, along with the information obtained from sequence similarity. A rationale for combining these diverse information sources was derived, and analyses of the information available from codon utilization in several species were performed, with wide variation seen. Codon bias information was found on average to improve the sensitivity of detection of short coding regions of human origin by about a factor of 5. The implications of combining information sources on the interpretation of positive findings are discussed.

Algorithms↗

The Sulfinator: predicting tyrosine sulfation sites in protein sequences.

UNLABELLED: Protein tyrosine sulfation is an important post-translational modification of proteins that go through the secretory pathway. No clear-cut acceptor motif can be defined that allows the prediction of tyrosine sulfation sites in polypeptide chains. The Sulfinator is a software tool that can be used to predict tyrosine sulfation sites in protein sequences with an overall accuracy of 98%. Four different Hidden Markov Models were constructed, each of them specialized to recognize sulfated tyrosine residues depending on their location within the sequence: near the N-terminus, near the C-terminus, in the center of a window with a size of at least 25 amino acids, as well as in windows containing several tyrosine residues. AVAILABILITY: The Sulfinator is accessible at (http://www.expasy.org/tools/sulfinator/). SUPPLEMENTARY INFORMATION: Sulfinator documentation is accessible at (http://www.expasy.org/tools/sulfinator/sulfinator-doc.html).

Amino Acid Sequence↗

SUBTRACT: a computer program for modeling the process of subtractive hydridization.

We report on a new software tool, SUBTRACT, which allows the analysis of the possible strategies for an experiment based on a mathematical model of subtractive hybridization. The program helps the experimenter choose the optimal strategy and conditions for performing the reaction. The program allows the modeling of cDNA and genomic subtraction for different types of target DNA. SUBTRACT offers a friendly interface for the investigation of the dynamics of the process of subtractive hybridization, and for modifying different parameters and initial conditions. SUBTRACT allows the user to plot the values of interesting quantities as a function of the reaction time. The program runs under the Unix operating system on Sun-compatible computers.

Algorithms↗

Experimental Peptide Identification Repository (EPIR): an integrated peptide-centric platform for validation and mining of tandem mass spectrometry data.

LC MS/MS has become an established technology in proteomic studies, and with the maturation of the technology the bottleneck has shifted from data generation to data validation and mining. To address this bottleneck we developed Experimental Peptide Identification Repository (EPIR), which is an integrated software platform for storage, validation, and mining of LC MS/MS-derived peptide evidence. EPIR is a cumulative data repository where precursor ions are linked to peptide assignments and protein associations returned by a search engine (e.g. Mascot, Sequest, or PepSea). Any number of datasets can be parsed into EPIR and subsequently validated and mined using a set of software modules that overlay the database. These include a peptide validation module, a protein grouping module, a generic module for extracting quantitative data, a comparative module, and additional modules for extracting statistical information. In the present study, the utility of EPIR and associated software tools is demonstrated on LC MS/MS data derived from a set of model proteins and complex protein mixtures derived from MCF-7 breast cancer cells. Emphasis is placed on the key strengths of EPIR, including the ability to validate and mine multiple combined datasets, and presentation of protein-level evidence in concise, nonredundant protein groups that are based on shared peptide evidence.

Breast Neoplasms↗

The POPPs: clustering and searching using peptide probability profiles.

The POPPs is a suite of inter-related software tools which allow the user to discover what is statistically 'unusual' in the composition of an unknown protein, or to automatically cluster proteins into families based on peptide composition. Finally, the user can search for related proteins based on peptide composition. Statistically based peptide composition provides a view of proteins that is, to some extent, orthogonal to that provided by sequence. In a test study, the POPP suite is able to regroup into their families sets of approximately 100 randomised Pfam protein domains. The POPPs suite is used to explore the diverse set of late embryogenesis abundant (LEA) proteins.

Algorithms↗

ROC analysis for assessment of lesion detection performance in 3D PET: influence of reconstruction algorithms.

Image quality in positron emission tomography (PET) can be assessed with physical parameters, as spatial resolution and signal-to-noise ratio, or using psychophysical approaches, which include the observer performance and the considered task (ROC analysis). For PET in oncology, such a task is the detection of hot lesions. The aim of the present study was to assess the lesion detection performance due to adequate modeling of the scanner and the measurement process in the image reconstruction process. We compared the standard OSEM software of the manufacturer with a sophisticated fully 3D iterative reconstruction technique (USC MAP). A rectangular phantom with 6 oblique line sources in a homogeneous background (2.6 kBq/ml 18F) was imaged dynamically with an ECAT EXACT HR+ scanner in 3D mode. Reconstructed activity contrasts varied between 15 and 0, as the line sources were filled with 11C (3.2 MBq/ml). Measured attenuation and standard randoms, dead time, and scatter corrections of the manufacturer were employed. For the ROC analysis, a software tool presented a cut-out of the phantom (15 x 15 pixels) to two observers. These cut-outs were rated (5 classes) and the area Az under the ROC curve was determined as a measure of detection performance. The improvement for Az with USC MAP compared to the OSEM reconstructions ranged between 0.02 and 0.23 for signal-to-noise ratios of the background between 2.8 and 3.1 and lesion contrast between 2.1 and 4.2. This study demonstrates that adequate modeling of the measurement process in the reconstruction algorithm improves the detection of small hot lesions markedly.

Algorithms↗

iScout: an intelligent scout for accessing and navigating large image sets in a PACS.

A new software tool for PACS, called iScout (intelligent scout), has been developed and optimized for a radiology workstation. The purpose of iScout is to display an overview of a large image series, allowing the user to select images for priority downloading from a PACS server to a PACS workstation. This allows radiologists to reduce the delays that are associated with downloading hundreds or even thousands of images. Several schemes that semiautomatically manage the download process are presented along with tests to measure performance. The results of the tests confirm that priority downloading provides faster access to images in large image series and that the time savings increase in proportion to the study size.

Computer Systems↗

Automated evaluation of hip axis length for predicting hip fracture.

The hip axis length has been shown in previous studies to be predictive of hip fracture independent of age and femoral bone density. The first studies of hip axis length were performed by manual measurement of dual x-ray absorptiometry (DXA) scan printouts. In this study, an automated analysis procedure is defined using software tools provided by the DXA manufacturer. Manual and automatic hip axis length measurements in 198 women were highly correlated (r = 0.98). Because of scaling factors of the printout, the automatic measurement was 58% longer than the manual value. Precision of the automatic measurement, based upon triplicate DXA scans of 33 women, was 0.07 cm or 0.68%. To define normative data, the hip axis length was measured from femoral DXA scans of 471 female volunteers aged 40-92 scanned on 14 different Hologic QDR-1000 systems. Mean hip axis length was 10.5 cm, with a standard deviation of 0.62 cm. No significant relationship between hip axis length and age was found (r = 0.07, P = 0.15). Based on previously reported odds ratios corrected for femoral bone density, age, height, and weight, an automatic hip axis length measurement of 11.0 cm is associated with a twofold increase in hip fracture risk compared with a woman with an average hip axis length. A hip axis length value of 11.6 cm increases hip fracture risk by a factor of 4 compared with a woman with a normal hip dimension. We conclude that the hip axis length can be easily incorporated into existing DXA hip analysis software in combination with a bone density measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Dynamic contact maps of protein structures.

The two-dimensional contact map of interresidue distances is a visual analysis technique for protein structures. We present two standalone software tools designed to be used in combination to increase the versatility of this simple yet powerful technique. First, the program Structer calculates contact maps from three-dimensional molecular structural data. The contact map matrix can then be viewed in the graphical matrix-visualization program Dotter. Instead of using a predefined distance cutoff, we exploit Dotter's dynamic rendering control, allowing interactive exploration at varying distance cutoffs after calculating the matrix once. Structer can use a number of distance measures, can incorporate multiple chains in one contact map, and allows masking of user-defined residue sets. It works either directly with PDB files, or can use the MMDB network API for reading structures.

Computer Simulation↗

Web-based self-assessments in pathology with Questionmark Perception.

Formative assessment with appropriate feedback is an effective method of promoting learning. Software tools are now available to facilitate the delivery of formative self-assessments via the World Wide Web. For the past 5 years, we have offered on-line formative self-assessments in pathology to undergraduate medical students. These assessments, which have been authored using Questionmark Perception, have proved particularly popular and have received high ratings in course evaluation surveys. Furthermore, they appear to have been effective in promoting student learning, with evidence that students made a genuine attempt to answer the questions in the assessment and that they learnt from doing so. The potential of on-line formative self-assessments for postgraduate training and continuing education in pathology so far remains untapped.

Computer-Assisted Instruction↗

Development and evaluation of different methods to assess download and display time of image web systems.

OBJECTIVES: The aim of this study was to develop and verify different methods of measuring time-to-display (TTD) for radiological images with image web systems (IWS). The process should be automatable in order to repeatedly perform a large number of measurements without human interaction. MATERIALS AND METHODS: Three methods were defined and compared with respect to usability, stability, and quality of results. Method 1 was based on Windows 2000 Performance Monitor, whereas method 2 employed phototransistors taped to the screen and connected to a separate PC. A software tool developed for method 3, which used Windows application programming interface (API) function, calls to read the color code assigned to specific pixels on the screen. RESULTS: Method 3 proved to be the most reliable and easy to automate. The accuracy is practically equivalent to method 2, but it proved to be far more automatable. Method 1 produced the largest mean error, was easily disturbed, but was also easy to set up and provided additional insights into the system's architecture especially if combined with method 3. CONCLUSIONS: To measure the performance of image distribution systems, any of these methods can be used, but method 3 proved to be superior.

Data Compression↗

Backbone solution structures of proteins using residual dipolar couplings: application to a novel structural genomics target.

Structural genomics (or proteomics) activities are critically dependent on the availability of high-throughput structure determination methodology. Development of such methodology has been a particular challenge for NMR based structure determination because of the demands for isotopic labeling of proteins and the requirements for very long data acquisition times. We present here a methodology that gains efficiency from a focus on determination of backbone structures of proteins as opposed to full structures with all sidechains in place. This focus is appropriate given the presumption that many protein structures in the future will be built using computational methods that start from representative fold family structures and replace as many as 70% of the sidechains in the course of structure determination. The methodology we present is based primarily on residual dipolar couplings (RDCs), readily accessible NMR observables that constrain the orientation of backbone fragments irrespective of separation in space. A new software tool is described for the assembly of backbone fragments under RDC constraints and an application to a structural genomics target is presented. The target is an 8.7 kDa protein from Pyrococcus furiosus, PF1061, that was previously not well annotated, and had a nearest structurally characterized neighbor with only 33% sequence identity. The structure produced shows structural similarity to this sequence homologue, but also shows similarity to other proteins, which suggests a functional role in sulfur transfer. Given the backbone structure and a possible functional link this should be an ideal target for development of modeling methods.

Amino Acid Sequence↗

Matrix2png: a utility for visualizing matrix data.

UNLABELLED: We describe a simple software tool, 'matrix2png', for creating color images of matrix data. Originally designed with the display of microarray data sets in mind, it is a general tool that can be used to make simple visualizations of matrices for use in figures, web pages, slide presentations and the like. It can also be used to generate images 'on the fly' in web applications. Both continuous-valued and discrete-valued (categorical) data sets can be displayed. Many options are available to the user, including the colors used, the display of row and column labels, and scale bars. In this note we describe some of matrix2png's features and describe some places it has been useful in the authors' work. AVAILABILITY: A simple web interface is available, and Unix binaries are available from http://microarray.cpmc.columbia.edu/matrix2png. Source code is available on request.

Color↗

ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences.

BACKGROUND: Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems--hence the need to develop novel strategies. RESULTS: We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. CONCLUSION: Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at http://aspic.algo.disco.unimib.it/aspic-devel/.

Algorithms↗

A genome-wide coverage-based pipeline for the identification of host-derived candidate DNA biomarkers from cell-free blood.

We have created a new data-analysis pipeline for the discovery of host-specific candidate DNA biomarkers derived from sequencing data of cell-free blood. Unlike approaches that rely on specific molecular or genetic signatures, our method leverages the coverage distribution of cell-free DNA sequences mapped to a reference genome, applying statistical analyses to identify informative short genomic regions for biomarker discovery. The pipeline is applicable to diverse diseases and can be used to analyze cell-free DNA sequences from plasma or serum to identify candidate biomarkers that are characteristic of disease states in mammals. Core functionalities were developed in Java and integrated with open-source software tools for the preprocessing of raw sequencing data, complemented by Python scripts for the machine-learning analysis and statistical validation. The pipeline is designed for HPC use and users can access the pipeline through a Galaxy workflow, which offers a user-friendly web interface for input selection prior to execution and analysis progress monitoring. Performance tests, carried out using duplicate sets of COVID-19 samples and controls, showed linear scalability of execution time with an increasing dataset size, as well as a substantial reduction in execution time through parallelized computation, whereby each HPC node is used to process the data of one chromosome. Further statistical tests confirmed the quality of the pipeline's results by showing that the set of identified candidate biomarkers remained stable across varying dataset sizes.

Biomarkers↗

Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR.

The human beta-globin locus is home to five genes that are regulated in a tissue-specific and developmental stage-specific manner. While the exact mode of expression remains somewhat enigmatic, a significant effort has been focused at the locus control region (LCR). The LCR is marked by five DNase I-hypersensitive sites (HS) approximately 15 kb upstream of the epsilon-globin gene. Nuclear matrix-associated regions (MARs) organize chromatin into functional domains and at least one of the HS appears bound to the nuclear matrix. We have employed an in vivo based PCR MAR assay to investigate the role of MAR-mediated regulation of the beta-globin locus. This was facilitated with a novel reaction efficiency based quantitative real-time PCR analysis software tool, Target Analysis Quantification. Using a log-linear regression strategy, discordances were eliminated. This allowed us to reliably estimate the relative amount of initial template associated with the nuclear matrix at 15 unique regions spanning the beta-globin locus in both non-expressing and expressing cell lines. A dynamic association dependent on expression status was revealed both at the LCR/5'HS region and within the second intron of the beta-globin gene. These results provide the first evidence that nuclear matrix association dynamically mediates the looping of the beta-globin locus to achieve transcriptional control.

Cell Line↗