SEARCH · Search PubMed

Results for “Ensemble methods”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed2004

Bayesian ensemble approach to error estimation of interatomic potentials.

Using a Bayesian approach a general method is developed to assess error bars on predictions made by models fitted to data. The error bars are estimated from fluctuations in ensembles of models sampling the model-parameter space with a probability density set by the minimum cost. The method is applied to the development of interatomic potentials for molybdenum using various potential forms and databases based on atomic forces. The calculated error bars on elastic constants, gamma-surface energies, structural energies, and dislocation properties are shown to provide realistic estimates of the actual errors for the potentials.

Bayes Theorem↗

PubMed2002

Gene expression data analysis of human lymphoma using support vector machines and output coding ensembles.

The large amount of data generated by DNA microarrays was originally analysed using unsupervised methods, such as clustering or self-organizing maps. Recently supervised methods such as decision trees, dot-product support vector machines (SVM) and multi-layer perceptrons (MLP) have been applied in order to classify normal and tumoural tissues. We propose methods based on non-linear SVM with polynomial and Gaussian kernels, and output coding (OC) ensembles of learning machines to separate normal from malignant tissues, to classify different types of lymphoma and to analyse the role of sets of coordinately expressed genes in carcinogenic processes of lymphoid tissues. Using gene expression data from "Lymphochip", a specialised DNA microarray developed at Stanford University School of Medicine, we show that SVM can correctly separate normal from tumoural tissues, and OC ensembles can be successfully used to classify different types of lymphoma. Moreover, we identify a group of coordinately expressed genes related to the separation of two distinct subgroups inside diffuse large B-cell lymphoma (DLBCL), validating a previous Alizadeh's hypothesis about the existence of two distinct diseases inside DLBCL.

Artificial Intelligence↗

PubMed1998

Improved anti-G protection boosts sortie generation ability.

BACKGROUND: There is a need for evaluation of new G protection equipment. HYPOTHESIS: There is no difference between the two anti-G ensembles on affecting subjects' ability to tolerate multiple simulated aerial combat sorties. METHODS: There were 15 subjects wearing the standard CSU-13 B/P anti-G ensemble (STD) or COMBAT EDGE/ATAGS (CE/ATAGS) ensemble who were exposed to 3 centrifuge-based simulated air combat sorties during a 2-h period. Each sortie consisted of four different G-profiles: 1) a gradual onset profile; 2) simulated air combat maneuver consisting of +4.5 to +7 Gz plateaus (4.5-7 SACM); 3) simulated air combat maneuver derived from actual fighter maneuvers with peaks up to +9 Gz (TACM); 4) simulated air combat maneuver consisting of +5.0 to +9.0 Gz plateaus (5-9 SACM). Each sortie was separated by a 20-min rest period. We measured heart rate, peripheral light loss (PLL), subjective effort level, subjective fatigue level, and reported recovery time. RESULTS: There were no incidents of unintended G-induced loss of consciousness (G-LOC) with CE/ATAGS. There were four incidents of unintended G-LOC with STD. At the end of the third sortie, with CE/ATAGS, mean heart rate was lower during the 4.5-7 SACM (p < 0.001) and the TACM (p < 0.001); PLL was less during all three rapid onset profiles (p < 0.01); subjects reported less effort during the 4.5-7 SACM (p < 0.001), the TACM and the 5-9 SACM (p < 0.01); reported fatigue was significantly lower (p < 0.001); and reported recovery times were nearly halved (p < 0.01). CONCLUSION: CE/ATAGS provided significantly greater G-protection than the standard anti-G ensemble. There was no G-LOC with CE/ATAGS. This greater protection should be of significant operational value in enhancing sortie generation capability by increasing fighter aircrew G-tolerance and decreasing aircrew fatigue.

Adult↗

PubMed2006

Phase transitions and criticality in small systems: vapor-liquid transition in nanoscale spherical cavities.

Phase transformations in fluids confined to nanoscale pores, which demonstrate characteristic signatures of first-order phase transitions, have been extensively documented in experiments and molecular simulations. They are characterized by a pronounced hysteresis, which disappears above a certain temperature. A rigorous interpretation of these observations represents a fundamental problem from the point of view of statistical mechanics. Nanoscale systems are essentially small, finite volume systems, in which the concept of the thermodynamic limit is no longer valid, and the statistical ensembles are not equivalent. Here, we present a rigorous approach to the description and molecular simulations of phase transitions and criticality in small confined systems, as illustrated by the example of vapor-liquid transition (capillary condensation) in spherical cavities. The method is based on the analysis of the canonical ensemble isotherms, which can be generated by the gauge cell Monte Carlo simulation method. The method allows one to define the critical temperature of phase transition, conditions of phase equilibrium, limits of stability of metastable states, and nucleation barriers, which determine hysteretic phase transformations.

Journal Article↗

PubMed2007

Application of single molecule Förster resonance energy transfer to protein folding.

Protein folding is a process characterized by a large degree of conformational heterogeneity. In such cases, classical experimental methods yield only mean values, averaged over large ensembles of molecules. The microscopic distributions of conformations, trajectories, or sequences of events often remain unknown, and with them the underlying molecular mechanisms. Signal averaging can be avoided by observing individual molecules. A particularly versatile method is highly sensitive fluorescence detection. In combination with Förster resonance energy transfer, distances and conformational dynamics can be investigated in single molecules. This chapter introduces the practical aspects of applying this method to protein folding.

Chromatography, High Pressure Liquid↗

PubMed2003

Enhanced diffusion-edited NMR spectroscopy of mixtures using chromatographic stationary phases.

We introduce an analytical method that combines in one pot the advantages of column chromatography separation and NMR structural analysis. The separation of the NMR spectra of the components of a mixture can be achieved according to their apparent diffusion rates [James, T. L. and McDonald, G. G. (1973) J. Magn. Reson. 58, 58-61]. We show that the separation of the spectral components, corresponding to single molecular species, can be enhanced by order of magnitudes upon addition of a typical stationary phase used in HPLC. The solid phase imbibed by the mixture for analysis is an heterogeneous ensemble, so that solid-state NMR methods (high-resolution magic angle spinning) are necessary to recover high-resolution spectra. We demonstrate applications of this combination of high-resolution magic angle spinning and NMR diffusometry on test mixtures for direct (silica gel) and inverse (C18) columns. However, many common chromatographic supports available for HPLC should be readily adaptable for use with this technique.

Journal Article↗

PubMed2005

Determination of nanocrystal sizes: a comparison of TEM, SAXS, and XRD studies of highly monodisperse CoPt3 particles.

One of the most fundamental tasks in nanoscience is the accurate determination of particle sizes. Various methods have been developed to elucidate the mean particle diameter and the standard deviation for an ensemble of nanocrystals. However, good agreement between the results from different methods is not always encountered in the literature. In this study, we investigate colloidally prepared, highly monodisperse CoPt3 nanoparticles by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and powder X-ray diffraction (XRD). The results are compared in order to examine to which extent agreement is obtained by the different techniques when applied to small nanocrystals in the size range below 10 nm. In particular, the applicability of the simple Scherrer formula for size determination from the broadening of XRD reflections is checked. When the different techniques are correctly applied, the results from all methods are in good agreement.

Journal Article↗

PubMed2004

Absolute quantification strategies in proteomics based on mass spectrometry.

The strong need for quantitative information in proteomics has fueled the development of mass spectrometry-based analytical methods that are able to determine protein abundances. This article reviews mass spectrometry experiments aimed at providing an absolute quantification of proteins. The experiments make use of the isotope-dilution concept by spiking a known amount of synthetic, isotope-labeled reference peptide into the analyte sample. Quantification is achieved by comparing the mass spectrometry signal intensities of the reference with an endogenous peptide that is generated upon proteolytic cleavage of the target protein. In an analogous manner, the level of post-translational modification at a distinct residue within a target protein can be determined. Among the strengths of absolute quantification are low detection limits reaching subfemtomole levels, a high dynamic range spanning approximately five orders of magnitude, low requirements for sample clean-up, and a fast and straightforward method development. Recent studies have demonstrated the compatibility of absolute quantification with various mass spectrometry readout techniques and sample purification steps such as 1D gel electrophoresis, size-exclusion chromatography, isoelectric peptide focusing, strong cation exchange and reversed phase or affinity chromatography. Under ideal conditions, quantification errors and coefficients of variation below 5% have been reported. However, the fact that at the start of the experiment the analyte is a protein and the internal standard is a peptide, severe quantification errors may result due to the selection of unsuitable reference peptides and/or imperfect protein proteolysis. Within the ensemble of mass spectrometry-based quantification methods, absolute quantification is the method of choice in cases where absolute numbers, many repetitive experiments or precise levels of post-translational modifications are required for a few, preselected species of interest. Consequently, prominent application areas include biomarker quantification, the study of post-translational modifications such as phosphorylation or ubiquitination and the comparison of concentrations of interacting proteins.

Amino Acid Sequence↗

PubMed1998

Optimizing energy potentials for success in protein tertiary structure prediction.

BACKGROUND: Success in solving the protein structure prediction problem relies on the choice of an accurate potential energy function. for a single protein sequence, it has been shown that the potential energy function can be optimized for predictive success by maximizing the energy gap between the correct structure and the ensemble of random structures relative to the distribution of the energies of these random structures (the Z-score). Different methods have been described for implementing this procedure for an ensemble of database proteins. Here, we demonstrate a new approach. RESULTS: For a single protein sequence, the probability of success (i.e the probability that the folded state is the lowest energy state) is derived. We then maximize the average probability of success for a set of proteins to obtain the optimal potential energy function. This results in maximum attention being focused on the proteins whose structures are difficult but not impossible to predict. CONCLUSIONS: Using a lattice model of proteins, we show that the optimal interaction potentials obtained by our method are both more accurate and more likely to produce successful predictions than those obtained by other averaging procedures.

Computer Simulation↗

PubMed2000

Unraveling the symmetry ambiguity in a hexamer: calculation of the R6 human insulin structure.

Crystallographic and NMR studies of insulin have revealed a highly flexible molecule with a range of different aggregation and structural states; the importance of these states for the function of the hormone is still unclear. To address this question, we have studied the solution structure of the insulin R6 symmetric hexamer using NMR spectroscopy. Structure determination of symmetric oligomers by NMR is complicated due to 'symmetry ambiguity' between intra- and intermonomer NOEs, and between different classes of intermonomer NOEs. Hence, to date, only two symmetric tetramers and one symmetric pentamer (VTB, B subunit of verotoxin) have been solved by NMR: there has been no other symmetric hexamer or higher-order oligomer. Recently, we reported a solution structure for R6 insulin hexamer. However, in that study, a crystal structure was used as a reference to resolve ambiguities caused by the threefold symmetry; the same method was used in solving VTB. Here, we have successfully recalculated R6 insulin using the symmetry-ADR method, a computational strategy in which ambiguities are resolved using the NMR data alone. Thus the obtained structure is a refinement of the previous R6 solution structure. Correlated motions in the final structural ensemble were analysed using a recently developed principal component method; this suggests the presence of two major conformational substates. The study demonstrates that the solution structure of higher-order symmetric oligomers can be determined unambiguously from NMR data alone, using the symmetry-ADR method. This success bodes well for future NMR studies of higher-order symmetric oligomers. The correlated motions observed in the structural ensemble suggest a new insight into the mechanism of phenol exchange and the T6 <--> R6 transition of insulin in solution.

Binding Sites↗

PubMed2006

A rate equation approach to elucidate the kinetics and robustness of the TGF-beta pathway.

We present a rate equation model for the TGF-beta pathway in endothelial cells together with novel measurements. This pathway plays a prominent role in inter- and intracellular communication and subversion can lead to cancer, fibrosis vascular disorders, and immune diseases. The model successfully describes the kinetics of experimental data and also correctly predicts the behavior in experiments where the system is perturbed. A novel method in this context, simulated tempering, is used to fit the model parameters to the data. It provides an ensemble of high quality solutions, which are analyzed with clustering methods and display a hierarchical structure highlighting distinct parameter subspaces with biological interpretations. This analysis discriminates between different biological mechanisms to achieve a transient signal from a sustained TGF-beta input, where one mechanism is to use a negative feedback to turn the signal off. Further analysis in terms of parameter sensitivity reveals that this negative feedback loop in TGF-beta signaling renders the system global robustness. This sheds light upon the role of the Smad7 protein in this system.

Computer Simulation↗

PubMed1987

Direct measurement of the velocity of the metachronal wave in beating cilia.

Recently a computerized electro-optical method was developed which enables one to simultaneously measure the frequency and the wavelength of the metachronal waves in beating cilia. The method is based on measurement of scattered light from two areas at a given distance apart. The distance between measured areas can be varied from zero to hundreds of microns. The relative ease of the measurement and data analysis of this method enable one to create large statistical ensembles in order to obtain reliable averages. In this work we show that in addition to the previously mentioned parameters this system can measure directly the velocity of the metachronal wave. It was found that the average velocity in the tissue culture from frog's palate epithelium at room temperature is approximately 270 micron/sec, about twice the average particle velocity at the frog's palate.

Animals↗

PubMed2004

Differences in hippocampal neuronal population responses to modifications of an environmental context: evidence for distinct, yet complementary, functions of CA3 and CA1 ensembles.

Understanding how the hippocampus processes information critical for establishing spatial and declarative memories will benefit greatly from determining not only what kind of information the hippocampus registers, but also how this information is processed across the different hippocampal subfields. We addressed this question using a novel immediate-early gene-based brain-imaging method (Arc/H1a catFISH) that allows comparisons of neuronal ensembles activated by two experiences separated by approximately 30 min. Rats exposed to the same environment twice activated CA3 and CA1 ensembles with a similarly high degree of overlap. Changing the identity or configuration of local cues, or changing distal cues, activated CA3 and CA1 ensembles with reduced overlap. Yet, the overlap was greater in CA3 than in CA1. In contrast, rats exposed to two completely different environments activated CA3 and CA1 ensembles with low overlap, and this overlap was even lower in CA3 compared with CA1. Thus, CA3 has a discontinuous, whereas CA1 has a graded, population response to alterations of an environment. Additionally, as indicated by the percentage of active neurons, the context representation was more sparse in CA3 (approximately 18%) than in CA1 (approximately 35%). Finally, CA3 and CA1 activity levels were not correlated within a session, arguing against a simple coactivation of these regions. Instead, the within-rat ratio of CA3/CA1 cell activity was correlated across sessions, suggesting that the balance of CA3/CA1 activity is individual specific. Taken together, these findings suggest that CA3 and CA1 neuronal ensembles perform distinct, yet complementary, functions in the processing of spatial and contextual information.

Animals↗

PubMed2000

Mapping of statistical physics to information theory with application to biological systems.

The problem of achieving a mapping of formalisms in statistical physics and theoretical biology to information theory is discussed using an example for canonical ensembles. We extend the meaning of the Handscomb Monte-Carlo method to a general recipe for the transformation from a "configuration" space to a "sentence" space. The ensemble of "sentences" and its corresponding source uncertainty function are introduced. A possible mapping procedure based on a generalization of the Handscomb representation is described. For a biological illustration, we present a way to introduce a pathway representation to describe metabolic processes in living systems.

Animals↗

PubMed2003

The revision of the model of primary energy conversion in purple bacteria.

A simulation method is suggested which enables one to check whether a model for excitation energy exchange in an ensemble of dye molecules fits available experimental data. In particular, this method may deal with photosynthetic units (PSUs) in which excitation migration in antenna chlorophylls and their substantial trapping in reaction centers (RCs) take place. Its application to the purple bacteria has proved that the model, which was generally accepted during the last 20-30 years, is in contradiction with recent experimental facts and thus requires modernization. Two physical mechanisms are discussed: femtosecond polarization of mobile hydrogen atoms near the reaction center special pair ("water latch"), and the presence of excitons delocalized over several core-bacteriochlorophylls (BChls). Our considerations give evidence that neither of these mechanisms alone can resolve the conflict, but their cumulative action appears to be sufficient. Unfortunately, these mechanisms were as yet only partially addressed experimentally.

Bacteriochlorophylls↗

PubMed2004

Do alternate methods of analysing motor evoked potentials give comparable results?

This study assessed the reliability of alternate methods of analysis of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We recorded two sets of MEPs (Time 1 and Time 2) at the optimal scalp sites for both the right first dorsal interosseous (FDI) and flexor carpi ulnaris (FCU) at two different stimulation intensities in 10 healthy subjects. MEP magnitude was determined in each of the following three ways: the mean peak-to-peak amplitude and area of the 20 individual responses; the amplitude and area of the ensemble averaged waveform; and the amplitude and area of the maximal response. There was no significant difference in amplitude or area for either muscle using any of the three methods between Time 1 and 2. However, the ensemble average (area and amplitude) was significantly smaller that the mean MEP, and the maximal MEP amplitude was significantly larger. Intraclass correlation analysis demonstrated that reliability of MEP measures over time was poor regardless of method. Reliability was similar between methods for FDI, but FCU had lower reliability values for the mean and ensemble average methods than the maximal method.

Adult↗

PubMed2003

Simulating structural and thermodynamic properties of carcinogen-damaged DNA.

A pair of stereoisomeric covalent adducts to guanine in double-stranded DNA, derived from the reaction of mutagenic and tumorigenic metabolites of benzo[a]pyrene, have been well characterized structurally and thermodynamically. Both high-resolution NMR solution structures and an array of thermodynamic data are available for these 10S (+)- and 10R (-)-trans-anti -[BP]-N(2)-dG adducts in double-stranded deoxyoligonucleotides. The availability of experimentally well-characterized duplexes containing these two stereoisomeric guanine adducts provides an opportunity for evaluating the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method for computing thermodynamic properties from molecular dynamics ensembles. We have carried out 3-ns molecular dynamics simulations, using NMR solution structures as the starting models for the 10S (+)- and 10R (-)-trans-anti-dG adducts in a DNA duplex 11-mer using AMBER 6.0. We employed the MM-PBSA method to compute the free energies, enthalpies, and entropies of the two adducts. Our complete thermodynamic analysis agrees quite well with the full experimental thermodynamic characterization of these adducts, showing essentially equal stabilities of the two adducts. We also calculated the nuclear Overhauser effect (NOE) distances from the molecular dynamics trajectories, and compared them against the experimental NMR-derived NOE distances. Our results showed that the simulated structures are in good agreement with the NMR experimental NOE data. Furthermore, the molecular dynamics simulations provided new structural and biological insights. Specifically, the puzzling observation that the BP aromatic ring system in the 10S (+)-trans-anti-dG adduct is more exposed to the aqueous solvent than the 10R (-)-trans-anti-dG adduct, is rationalized in terms of the adduct structures. The structural and thermodynamic features of these stereoisomeric adducts are also discussed in relation to their reported low susceptibilities to nucleotide excision repair.

Base Sequence↗

PubMed2002

Automated detection and elimination of periodic ECG artifacts in EEG using the energy interval histogram method.

An automated method for electrocardiogram (ECG)-artifact detection and elimination is proposed for application to a single-channel electroencephalogram (EEG) without a separate ECG channel for reference. The method is based on three characteristics of ECG artifacts: the spike-like property, the periodicity and the lack of correlation with the EEG. The method involves a two-step process: ECG artifact detection using the energy interval histogram (EIH) method and ECG artifact elimination using a modification of ensemble average subtraction. We applied a smoothed nonlinear energy operator to the contaminated EEG, which significantly emphasized the ECG artifacts compared with the background EEG. The EIH method was initially proposed to estimate the rate of false positives (FPs) and false negatives (FNs) that were necessary to determine the optimal threshold for the detection of the ECG artifact. As a postprocessing step, we used two types of threshold adjusting algorithms that were based on the periodicity of the ECG R-peaks. The technique was applied to four whole-night sleep EEG recordings from four subjects with severe obstructive sleep apnea syndrome, from which a total of 132878 heartbeats were monitored over 31.8 h. We found that ECG artifacts were successfully detected and eliminated with FP = 0.017 and FN = 0.074 for the epochs where the elimination process is necessarily required.

Algorithms↗