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SEQOPTICS: a protein sequence clustering system.

BACKGROUND: Protein sequence clustering has been widely used as a part of the analysis of protein structure and function. In most cases single linkage or graph-based clustering algorithms have been applied. OPTICS (Ordering Points To Identify the Clustering Structure) is an attractive approach due to its emphasis on visualization of results and support for interactive work, e.g., in choosing parameters. However, OPTICS has not been used, as far as we know, for protein sequence clustering. RESULTS: In this paper, a system of clustering proteins, SEQOPTICS (SEQuence clustering with OPTICS) is demonstrated. The system is implemented with Smith-Waterman as protein distance measurement and OPTICS at its core to perform protein sequence clustering. SEQOPTICS is tested with four data sets from different data sources. Visualization of the sequence clustering structure is demonstrated as well. CONCLUSION: The system was evaluated by comparison with other existing methods. Analysis of the results demonstrates that SEQOPTICS performs better based on some evaluation criteria including Jaccard coefficient, Precision, and Recall. It is a promising protein sequence clustering method with future possible improvement on parallel computing and other protein distance measurements.

Algorithms↗

Analysis of scanning probe microscope images using wavelets.

The utility of wavelet transforms for analysis of scanning probe images is investigated. Simulated scanning probe images are analyzed using wavelet transforms and compared to a parallel analysis using more conventional Fourier transform techniques. The wavelet method introduced in this paper is particularly useful as an image recognition algorithm to enhance nanoscale objects of a specific scale that may be present in scanning probe images. In its present form, the applied wavelet is optimal for detecting objects with rotational symmetry. The wavelet scheme is applied to the analysis of scanning probe data to better illustrate the advantages that this new analysis tool offers. The wavelet algorithm developed for analysis of scanning probe microscope (SPM) images has been incorporated into the WSxM software which is a versatile freeware SPM analysis package.

Algorithms↗

Combined therapy for obese type 2 diabetes: suppertime mixed insulin with daytime sulfonylurea.

Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin, thereby postponing the need for multiple injections. This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked, placebo-controlled, parallel design, 16-week protocol. Premixed 70% NPH/30% Regular insulin was taken before supper, and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia. Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo (mean +/- SEM; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L; p less than 0.05), and had a greater decrement of glycosylated hemoglobin from baseline values (1.3 +/- 0.1 versus 0.8 +/- 0.2% A1, p less than 0.05). After 16 weeks the combined therapy group used half as much insulin as the insulin-only group (50 +/- 5 versus 101 +/- 13 units/d; p less than 0.01). Fasting serum free insulin values increased 58% from baseline after insulin therapy in the insulin-only group (p less than 0.05) but did not increase with combined therapy. Weight gain was similar in the two groups. These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone.

Adult↗

Distributed vector processing of a new local multiscale Fourier transform for medical imaging applications.

The recently developed S-transform (ST) combines features of the Fourier and Wavelet transforms; it reveals frequency variation over both space and time. It is a potentially powerful tool that can be applied to medical image processing including texture analysis and noise filtering. However, calculation of the ST is computationally intensive, making conventional implementations too slow for many medical applications. This problem was addressed by combining parallel and vector computations to provide a 25-fold reduction in computation time. This approach could help accelerate many medical image processing algorithms.

Algorithms↗

Piecewise exponential survival trees with time-dependent covariates.

Survival trees methods are nonparametric alternatives to the semiparametric Cox regression in survival analysis. In this paper, a tree-based method for censored survival data with time-dependent covariates is proposed. The proposed method assumes a very general model for the hazard function and is fully nonparametric. The recursive partitioning algorithm uses the likelihood estimation procedure to grow trees under a piecewise exponential structure that handles time-dependent covariates in a parallel way to time-independent covariates. In general, the estimated hazard at a node gives the risk for a group of individuals during a specific time period. Both cross-validation and bootstrap resampling techniques are implemented in the tree selection procedure. The performance of the proposed survival trees method is shown to be good through simulation and application to real data.

Biometry↗

Study of the point spread function (PSF) for 123I SPECT imaging using Monte Carlo simulation.

The iterative reconstruction algorithms employed in brain single-photon emission computed tomography (SPECT) allow some quantitative parameters of the image to be improved. These algorithms require accurate modelling of the so-called point spread function (PSF). Nowadays, most in vivo neurotransmitter SPECT studies employ pharmaceuticals radiolabelled with 123I. In addition to an intense line at 159 keV, the decay scheme of this radioisotope includes some higher energy gammas which may have a non-negligible contribution to the PSF. The aim of this work is to study this contribution for two low-energy high-resolution collimator configurations, namely, the parallel and the fan beam. The transport of radiation through the material system is simulated with the Monte Carlo code PENELOPE. We have developed a main program that deals with the intricacies associated with tracking photon trajectories through the geometry of the collimator and detection systems. The simulated PSFs are partly validated with a set of experimental measurements that use the 511 keV annihilation photons emitted by a 18F source. Sensitivity and spatial resolution have been studied, showing that a significant fraction of the detection events in the energy window centred at 159 keV (up to approximately 49% for the parallel collimator) are originated by higher energy gamma rays, which contribute to the spatial profile of the PSF mostly outside the 'geometrical' region dominated by the low-energy photons. Therefore, these high-energy counts are to be considered as noise, a fact that should be taken into account when modelling PSFs for reconstruction algorithms. We also show that the fan beam collimator gives higher signal-to-noise ratios than the parallel collimator for all the source positions analysed.

Fluorine Radioisotopes↗

Optimal electron and combined electron and photon therapy in the phase space of complication-free cure.

The possibility of using intensity-modulated high-energy electrons beams alone or in combination with photon beams to treat tumours located at depths from 5 cm to 25 cm has been investigated. A radiobiologically based optimization algorithm using the probability of complication-free tumour control has been used to calculate the optimal dose distributions. Two different target volumes have been used; one advanced cervical cancer with locally involved lymph nodes and one astrocytoma in the upper brain hemisphere. Treatments with only electron beams and also combinations between electron and photon beams have been investigated. The dependence of the expected treatment outcome on the beam energy and directions was investigated, and to some extent on the number of beam portals. It is shown that the beam direction intervals resulting in a high expected treatment outcome increase with increasing electron energy and also with some electron-photon combinations. For an eccentrically placed, not too deeply situated tumour surrounded by sensitive normal tissue it is shown that the expected treatment outcome can be improved by using electron beams in combination with photon beams compared with using two photon beams, and using two electron beams results in almost as high an expected treatment outcome. The possibility of improving the dose conformity from electron beams by adding photon fields parallel or orthogonal to the electron beams is demonstrated.

Algorithms↗

GARD: a genetic algorithm for recombination detection.

MOTIVATION: Phylogenetic and evolutionary inference can be severely misled if recombination is not accounted for, hence screening for it should be an essential component of nearly every comparative study. The evolution of recombinant sequences can not be properly explained by a single phylogenetic tree, but several phylogenies may be used to correctly model the evolution of non-recombinant fragments. RESULTS: We developed a likelihood-based model selection procedure that uses a genetic algorithm to search multiple sequence alignments for evidence of recombination breakpoints and identify putative recombinant sequences. GARD is an extensible and intuitive method that can be run efficiently in parallel. Extensive simulation studies show that the method nearly always outperforms other available tools, both in terms of power and accuracy and that the use of GARD to screen sequences for recombination ensures good statistical properties for methods aimed at detecting positive selection. AVAILABILITY: Freely available http://www.datamonkey.org/GARD/

Algorithms↗

FAZYTAN: a system for fast automated cell segmentation, cell image analysis and feature extraction based on TV-image pickup and parallel processing.

Cell location, segmentation and feature extraction of cell images are principal tasks of a high-resolution system for automated cytology. To perform these tasks with high speed, image processing algorithms and the architecture of a processor have to be optimized mutually. This has led to the development of a fast system for the evaluation of cytologic samples based on an optimized TV microscope, a host minicomputer with different peripheral array processors and digital image storages. The processors are optimized in speed for two-dimensional local operations to investigate neighborhood relations and morphology in cell images. Two-dimensional transformations of TV images (288 x 512 x 8 bit) can be carried out within 20 to 200 msec. The processors are able to realize linear filter functions (correlation, convolution) as well as nonlinear functions (median filtering). A set of measurements like area, circumference and connectivity can be derived parallely from one image in 20 msec. The system performs efficient and fast detection and segmentation of cells scanned in one TV frame within one second as well as the extraction of a large number of morphologic features within a few seconds. Based on these procedures, high-resolution analysis of several thousand cells of a sample within one minute will be possible.

Autoanalysis↗

Specificity of two tests for the early diagnosis of bovine paratuberculosis based on cell-mediated immunity: the Johnin skin test and the gamma interferon assay.

Paratuberculosis in cattle is a chronic debilitating infectious disease caused by Mycobacterium paratuberculosis. Control of paratuberculosis is based on tests that principally detect advanced stages of infections: faecal culture and serology. Tests measuring cell-mediated immunity (CMI) could improve control of paratuberculosis if able to diagnose mycobacterial infections earlier, before animals become infectious. A drawback of CMI tests for paratuberculosis has been a reported low specificity. This study re-examined CMI specificity and factors that may affect it. The specificities of the Johnin skin test and its in vitro equivalent, the gamma interferon (IFNgamma) assay, were estimated in 35 uninfected dairy herds. In each herd a random sample of 20 young (6-24 months old) and 20 adult (> or =24 months old) female dairy cattle were tested by both tests simultaneously. Skin test specificity was 93.5% using a skin thickness increase of > or =4mm as the cut-off value. IFNgamma assay specificity when interpreted using a newly developed algorithm was 93.6%. When interpreted according to two alternative algorithms provided by the IFNgamma kit suppliers, the assay had specificities of 66.1 and 67.0%. If the skin test and IFNgamma assay were used in parallel, and only animals positive on both tests were considered as M. paratuberculosis-infected, the specificity was 97.6%. Agreement between skin test and IFNgamma assay on 1631 total animals was fair (kappa=0.41). Antigen batch influenced the specificity of both the skin test, ranging from 92 to 95%, and the IFNgamma assay, ranging from 71 to 99% among batches. Test specificity also varied among herds ranging from 58 to 100% for the skin test and 57 to 100% for the IFNgamma assay. While factors affecting CMI test specificity and agreement need further evaluation, the high specificity and general agreement among these CMI tests, coupled with the excellent results obtained in the control of bovine tuberculosis using CMI tests, support their potential value in the early diagnosis and control of paratuberculosis.

Algorithms↗

180 degree pinhole SPET with a tilted detector and OS-EM reconstruction: phantom studies and potential clinical applications.

This study investigated the feasibility of ordered subsets expectation maximisation (OS-EM) reconstruction of pinhole single-photon emission tomography (SPET) acquired with a tilted detector head and a 180 degrees orbit. Phantom and patient data were recorded using a standard single-head camera. Reconstructions were performed using a dedicated OS-EM algorithm. Reconstructed images of line, uniformity and Picker's thyroid phantoms showed that the geometry, physical size and uniformity of the radioactive objects were preserved. For the range of radius corresponding to the patient studies, the measured full-widths at half-maximum lay between 4.90+/-0.25 mm and 6.05+/-0.25 mm. Finally, the gain in resolution associated with the use of the pinhole collimator instead of a parallel-hole collimator was highlighted in a parathyroid exploration and in a shoulder bone study.

Aged↗

AUTO3DEM--an automated and high throughput program for image reconstruction of icosahedral particles.

AUTO3DEM is an automation system designed to accelerate the computationally intensive process of three-dimensional structure determination from images of vitrified icosahedral virus particles. With minimal user input and intervention, AUTO3DEM manages the flow of data between the major image reconstruction programs, monitors the progress of the computations, and intelligently updates the input parameters as the resolution of the model is improved. It is designed to be used on any computer running the Linux or UNIX operating systems and can be run in parallel mode on multi-processor systems.

Algorithms↗

Three-dimensional ultrasound imaging of the vasculature.

With conventional ultrasonography, the diagnostician must view a series of two-dimensional images in order to form a mental impression of the three-dimensional anatomy, an efficient and time consuming practice prone to operator variability, which may cause variable or even incorrect diagnoses. Also, a conventional two-dimensional ultrasound image represents a thin slice of the patients anatomy at a single location and orientation, which is difficult to reproduce at a later time. These factors make conventional ultrasonography non-optimal for prospective or follow-up studies. Our efforts have focused on overcoming these deficiencies by developing three-dimensional ultrasound imaging techniques that are capable of acquiring B-mode, colour Doppler and power Doppler images of the vasculature, by using a conventional ultrasound system to acquire a series of two-dimensional images and then mathematically reconstructing them into a single three-dimensional image, which may then be viewed interactively on an inexpensive desktop computer. We report here on two approaches: (1) free-hand scanning, in which a magnetic positioning device is attached to the ultrasound transducer to record the position and orientation of each two-dimensional image needed for the three-dimensional image reconstruction; and (2) mechanical scanning, in which a motor-driven assembly is used to translate the transducer linearly across the neck, yielding a set of uniformly-spaced parallel two-dimensional images.

Algorithms↗

Measuring parallelism, linearity, and relative potency in bioassay and immunoassay data.

There is often a need to determine parallelism or linearity between pairs of dose-response data sets for various biological applications. This article describes a technique based on a modification of the well-known extra-sum-of-squares principle of statistical regression. The standard extra-sum-of-squares method uses an F-distributed ratio as a statistic and an F-test based on this statistic as the parallelism test. It is shown here that this metric does not directly measure the parallelism between the two curves and can often vary in opposition to actual parallelism. To overcome this problem, a metric based on a chi-square test applied directly on the chi-square-distributed extra-sum-of-squares statistic is developed, which is shown to correspond directly to parallelism. This parallelism metric does not suffer from the shortcomings of the conventional F-test-based metric, and is a more reliable and appropriate measure of parallelism. The article also shows that the choice of curve model has a large effect on the sensitivity of either metric, and that using an asymmetric model, such as the asymmetric five-parameter logistic function, a generalization of the commonly used symmetric four-parameter logistic function, is necessary when working with asymmetric dose-response data. The effect of noise, as well as the importance of correct weighting on the parallelism metrics and the relative potency, is also studied.

Algorithms↗

Spatial filtering and neocortical dynamics: estimates of EEG coherence.

The spatial statistics of scalp electroencephalogram (EEG) are usually presented as coherence in individual frequency bands. These coherences result both from correlations among neocortical sources and volume conduction through the tissues of the head. The scalp EEG is spatially low-pass filtered by the poorly conducting skull, introducing artificial correlation between the electrodes. A four concentric spheres (brain, CSF, skull, and scalp) model of the head and stochastic field theory are used here to derive an analytic estimate of the coherence at scalp electrodes due to volume conduction of uncorrelated source activity, predicting that electrodes within 10-12 cm can appear correlated. The surface Laplacian estimate of cortical surface potentials spatially bandpass filters the scalp potentials reducing this artificial coherence due to volume conduction. Examination of EEG data confirms that the coherence estimates from raw scalp potentials and Laplacians are sensitive to different spatial bandwidths and should be used in parallel in studies of neocortical dynamic function.

Algorithms↗

Relevance of accurate Monte Carlo modeling in nuclear medical imaging.

Monte Carlo techniques have become popular in different areas of medical physics with advantage of powerful computing systems. In particular, they have been extensively applied to simulate processes involving random behavior and to quantify physical parameters that are difficult or even impossible to calculate by experimental measurements. Recent nuclear medical imaging innovations such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and multiple emission tomography (MET) are ideal for Monte Carlo modeling techniques because of the stochastic nature of radiation emission, transport and detection processes. Factors which have contributed to the wider use include improved models of radiation transport processes, the practicality of application with the development of acceleration schemes and the improved speed of computers. In this paper we present a derivation and methodological basis for this approach and critically review their areas of application in nuclear imaging. An overview of existing simulation programs is provided and illustrated with examples of some useful features of such sophisticated tools in connection with common computing facilities and more powerful multiple-processor parallel processing systems. Current and future trends in the field are also discussed.

Algorithms↗

Temporal and spatial response to second-order stimuli in cat area 18.

Temporal and spatial response to second-order stimuli in cat area 18. J. Neurophysiol. 80: 2811-2823, 1998. Approximately one-half of the neurons in cat area 18 respond to contrast envelope stimuli, consisting of a sinewave carrier whose contrast is modulated by a drifting sinewave envelope of lower spatial frequency. These stimuli should fail to elicit a response from a conventional linear neuron because they are designed to contain no spatial frequency components within the cell's luminance-defined frequency passband. We measured neurons' responses to envelope stimuli by varying both the drift rate and spatial frequency of the contrast modulation. These data were then compared with the same neurons' spatial and temporal properties obtained with luminance-defined sinewave gratings. Most neurons' responses to the envelope stimuli were spatially and temporally bandpass, with bandwidths comparable with those measured with luminance gratings. The temporal responses of these neurons (temporal frequency tuning and latency) were systematically slower when tested with envelope stimuli than with luminance gratings. The simplest kind of model that can accommodate these results is one having separate, parallel streams of bandpass processing for luminance and envelope stimuli.

Algorithms↗

Single-molecule three-color FRET.

Fluorescence resonance energy transfer (FRET) measured at the single-molecule level can reveal conformational changes of biomolecules and intermolecular interactions in physiologically relevant conditions. Thus far single-molecule FRET has been measured only between two fluorophores. However, for many complex systems, the ability to observe changes in more than one distance is desired and FRET measured between three spectrally distinct fluorophores can provide a more complete picture. We have extended the single-molecule FRET technique to three colors, using the DNA four-way (Holliday) junction as a model system that undergoes two-state conformational fluctuations. By labeling three arms of the junction with Cy3 (donor), Cy5 (acceptor 1), and Cy5.5 (acceptor 2), distance changes between the donor and acceptor 1, and between the donor and acceptor 2, can be measured simultaneously. Thus we are able to show that the acceptor 1 arm moves away from the donor arm at the same time as the acceptor 2 arm approaches the donor arm, and vice versa, marking the first example of observing correlated movements of two different segments of a single molecule. Our data further suggest that Holliday junction does not spend measurable time with any of the helices unstacked, and that the parallel conformations are not populated to a detectable degree.

Algorithms↗