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At least 289 records · Page 16Linked to original sources

Inferring gene regulatory networks from time series data using the minimum description length principle.

MOTIVATION: A central question in reverse engineering of genetic networks consists in determining the dependencies and regulating relationships among genes. This paper addresses the problem of inferring genetic regulatory networks from time-series gene-expression profiles. By adopting a probabilistic modeling framework compatible with the family of models represented by dynamic Bayesian networks and probabilistic Boolean networks, this paper proposes a network inference algorithm to recover not only the direct gene connectivity but also the regulating orientations. RESULTS: Based on the minimum description length principle, a novel network inference algorithm is proposed that greatly shrinks the search space for graphical solutions and achieves a good trade-off between modeling complexity and data fitting. Simulation results show that the algorithm achieves good performance in the case of synthetic networks. Compared with existing state-of-the-art results in the literature, the proposed algorithm exceptionally excels in efficiency, accuracy, robustness and scalability. Given a time-series dataset for Drosophila melanogaster, the paper proposes a genetic regulatory network involved in Drosophila's muscle development. AVAILABILITY: Available from the authors upon request.

Algorithms↗

Probability of conduction deficit as related to fiber length in random-distribution models of peripheral neuropathies.

This paper presents a set of probabilistic models which reproduce the proximodistal gradient of sensory deficit in peripheral neuropathies, on the basis of the occurrence of axonal dysfunction as a result of randomly distributed abnormalities. The models, which are based on conduction block, loss of temporal coherence, and weak interactions between nerve fibers, demonstrate that randomly distributed axonal dysfunction provides a sufficient condition for distal sensory deficit. The models predict a marked reduction in the length for normal sensory conduction with small increases in the probability of axomal dysfunction, providing a possible correlate for the rapid clinical progression of some neuropathies. The hypothesis that weak interactions between fibers result in paresthesiae in peripheral neuropathies is also discussed.

Humans↗

Modeling cellular systems and aging processes: I. Mathematics of cell system models-a review.

A review of the literature on mathematical models of populations of cellular systems is presented. Continuous, discrete, and stochastic models are presented in a semihistorical manner as a prelude to answering the question of how to model an asynchronously dividing cellular system. This analysis is then broadened, in an attempt to broach the more general question of modeling the distribution of a set or collection of cell properties through an asynchronously dividing cellular system. Such properties might be cell motility, cell cycle length, time to mitosis, or number of epigenetic particles. It is shown that one fruitful approach to this modeling question is a coupled continuous-probabilistic model. The ramifications of this type of formalism are discussed.

Aging↗

Radiation environment induced by cosmic ray particle fluxes in the International Space Station orbit according to recent galactic and solar cosmic ray models.

Radiation characteristics (particle fluxes, doses, and LET spectra) are calculated for spacecraft in the International Space Station orbit. The calculations are made in terms of the dynamic model for galactic cosmic rays and the probabilistic model for solar cosmic rays developed at the Institute of Nuclear Physics of Moscow State University.

Cosmic Radiation↗

Modelling behavioral syndromes using Bayesian networks.

In this paper Bayesian networks modelling is applied to a multidimensional model of depression. The characterization of the probabilistic model exploits expert knowledge to associate latent concentrations of neurotransmitters and symptoms. An evolution perspective is also considered. Specific criteria are introduced to detect the influence of the latent variable on the observation of symptoms. The Bayesian analysis is carried out using Gibbs sampling technique which is implemented in the BUGS software. The estimation phase leads to the selection of symptoms entering into the definition of behavioral syndromes. Results on real data are discussed. The last section deals with simulation experiments. Simulation results confirm our methodological choices. Results of the paper can enlarge to the central problem of the management of latent variables in Bayesian networks modelling.

Artificial Intelligence↗

Enhanced protein domain discovery by using language modeling techniques from speech recognition.

Most modern speech recognition uses probabilistic models to interpret a sequence of sounds. Hidden Markov models, in particular, are used to recognize words. The same techniques have been adapted to find domains in protein sequences of amino acids. To increase word accuracy in speech recognition, language models are used to capture the information that certain word combinations are more likely than others, thus improving detection based on context. However, to date, these context techniques have not been applied to protein domain discovery. Here we show that the application of statistical language modeling methods can significantly enhance domain recognition in protein sequences. As an example, we discover an unannotated Tf_Otx Pfam domain on the cone rod homeobox protein, which suggests a possible mechanism for how the V242M mutation on this protein causes cone-rod dystrophy.

Algorithms↗

Preferential flow in municipal solid waste and implications for long-term leachate quality: valuation of laboratory-scale experiments.

In this paper, we study and quantify pollutant concentrations after long-term leaching at relatively low flow rates and residual concentrations after heavy flushing of a 0.14 m3 municipal solid waste sample. Moreover, water flow and solute transport through preferential flow paths are studied by model interpretation of experimental break-through curves (BTCs), generated by tracer tests. In the study it was found that high concentrations of chloride remain after several pore volumes of water have percolated through the waste sample. The residual concentration was found to be considerably higher than can be predicted by degradation models. For model interpretations of the experimental BTCs, two probabilistic model approaches were applied, the transfer function model and the Lagrangian transport formulation. The experimental BTCs indicated the presence of preferential flow through the waste mass and the model interpretation of the BTCs suggested that between 19 and 41% of the total water content participated in the transport of solute through preferential flow paths. In the study, the occurrence of preferential flow was found to be dependent on the flow rate in the sense that a high flow rate enhances the preferential flow. However, to fully quantify the possible dependence between flow rate and preferential flow, experiments on a broader range of experimental conditions are suggested. The chloride washout curve obtained over the 4-year study period shows that as a consequence of the water flow in favoured flow paths, bypassing other parts of the solid waste body, the leachate quality may reflect only the flow paths and their surroundings. The results in this study thus show that in order to improve long-term prediction of the leachate quality and quantity the magnitude of the preferential water flow through a landfill must be taken into account.

Chlorides↗

Modeling the level of contamination of Staphylococcus aureus in ready-to-eat kimbab in Korea.

The risk of Staphylococcus aureus in ready-to-eat kimbab (rice rolled in laver) sold in Korea was evaluated by a mathematical modeling approach. Four nodes were constructed from preparation at retail to consumption. A predictive microbial growth model and survey data were combined with probabilistic modeling to simulate the level of S. aureus in a single kimbab at the time of consumption. We estimated the mean level of S. aureus to be 2.92 log CFU/g for a typical kimbab (150 to 200 g each) at the time of consumption. Our model also showed that 29.73% of the kimbabs had > or = 100,000 S. aureus CFU/g, which poses some risk of illness, since some level of enterotoxin would be expected from toxigenic strains. However, because of the lack of dose-response models for staphylococcal enterotoxin, the final level of S. aureus in the kimbabs could not be used to estimate how many people would become ill from eating them. Correlation sensitivity results showed that consumer eating patterns and initial contamination levels at retail stores were the most significant risk factors for illness and that temperature control under 10 degrees C was a critical control point in kimbab retail establishments to prevent the growth of S. aureus.

Colony Count, Microbial↗

Lessons learned studying design issues for lunar and Mars settlements.

In a study of lunar and Mars settlement concepts, an analysis was made of fundamental design assumptions in five technical areas against a model list of occupational and environmental health concerns. The technical areas included the proposed science projects to be supported, habitat and construction issues, closed ecosystem issues, the "MMM" issues (mining, material processing, and manufacturing), and the human elements of physiology, behavior, and mission approach. Four major lessons were learned. First it is possible to relate public health concerns to complex technological development in a proactive design mode, which has the potential for long-term cost savings. Second, it became very apparent that prior to committing any nation or international group to spending the billions to start and complete a lunar settlement, over the next century, that a significantly different approach must be taken from those previously proposed, to solve the closed ecosystem and "MMM" problems. Third, it also appears that the health concerns and technology issues to be addressed for human exploration into space are fundamentally those to be solved for human habitation of the Earth (as a closed ecosystem) in the 21st century. Finally, it is proposed that ecosystem design modeling must develop new tools, based on probabilistic models as a step up from closed circuit models.

Aerospace Medicine↗

A generalized HLA prediction model for related donor matches.

This article derives a generalized probabilistic model for predicting HLA matches from a population of family members consisting of all blood-related descendants of one pair of patient's grandparents, excluding parents and siblings, for three subsequent generations. This consists of the patient's children, blood-related aunts/uncles, first cousins, first cousins once removed and nephews/nieces. (It is assumed that the patient's siblings and parents were tested prior but did not produce a match.) The model uses family pedigree information and haplotype frequency data to estimate the likelihood of a match. Results are given for many ethnic groupings. These results indicate that such a family search frequently approximates or exceeds the 0.25 success rate of a single sibling search when the patient possesses a common haplotype within the patient's ethnic population, and the family members are also of the same ethnic origin. Families of the same lineage averaging more than two children/nuclear family substantially exceed the 0.25 rate. The results degrade only modestly for the two children/nuclear family scenario when first cousins once removed are excluded from the search. Among the study's larger nations of Japan, the United States and the United Kingdom, approximately 15-20% of the population can potentially benefit from such searches. These percentages are much higher for the study's smaller countries.

HLA Antigens↗

Economic evaluation of tiotropium and salmeterol in the treatment of chronic obstructive pulmonary disease (COPD) in Greece.

OBJECTIVE: The objective of the study was to assess the cost-effectiveness of two therapeutic alternatives for chronic obstructive pulmonary disease in the Greek National Health Service (NHS) setting. METHODS: A Markov probabilistic model was used to compare tiotropium with salmeterol. A Monte Carlo simulation with 5000 cases was run in the probabilistic analysis. The model was designed to compute the expected time spent in each state, the expected number of exacerbations occurring and the expected treatment cost per patient. Probabilities were extracted from clinical trials, resource utilisation and cost data from a Greek university hospital. RESULTS: Quality adjusted life years were 0.70 (95% Uncertainty Interval [UI]: 0.63 to 0.77) in the tiotropium arm and 0.68 (95% UI: 0.60 to 0.75) in the salmeterol arm; a difference of 0.02 (95% UI: -0.08 to 0.13). Exacerbations reached 0.85 (95% UI: 0.80 to 0.91) in the tiotropium arm and 1.02 (95% UI: 0.84 to 1.21) in the salmeterol arm, a difference of -0.17 (95% UI: -0.37 to 0.02). Estimates of the mean annual cost per patient were euro2504 (euro2122 to euro2965) in the tiotropium arm and euro2655 (euro2111 to euro3324) in the salmeterol arm, a difference of -euro151 (-euro926 to euro580). Stochastic analysis showed that tiotropium may have an advantage in reducing exacerbations. The probability that tiotropium is cost-effective was 65% at a ceiling value of euro0 and reached 77% at a ceiling ratio of euro1000. Results stay fairly constant in various sensitivity analyses. CONCLUSION: Even though tiotropium is more expensive to buy than salmeterol in the Greek NHS (using Greek costs there was no statistically significant difference in total costs between tiotropium and salmeterol), overall, during the course of a year, it is actually associated with a lower prevalence of exacerbations and lower treatment costs and thus may represent a viable and cost-effective alternative in the Greek NHS setting.

Albuterol↗

Multiple reservoir model of neurotransmitter release by a cochlear inner hair cell.

A probabilistic model is described for transmitter release from hair cells, auditory neuron EPSP's, and discharge patterns. The present model assumes that several reservoirs of neurotransmitter exist, having individual probability-of-release functions centered at successively higher intensities. The model accurately mimics the adaptation of successive EPSP amplitudes of the afferent neuron of the goldfish sacculus and, for mammalian auditory-nerve fibers, the adaptation of neural discharge rate, the saturation of onset and steady-state neural rate versus intensity, and the change in neural rate in response to incremental stimuli. The model also produces realistic interval and period histograms. The data shown support the hypothesis that multiple populations of neurotransmitter are involved in the afferent hair-cell synapses.

Action Potentials↗

Intensity-based protein identification by machine learning from a library of tandem mass spectra.

Tandem mass spectrometry (MS/MS) has emerged as a cornerstone of proteomics owing in part to robust spectral interpretation algorithms. Widely used algorithms do not fully exploit the intensity patterns present in mass spectra. Here, we demonstrate that intensity pattern modeling improves peptide and protein identification from MS/MS spectra. We modeled fragment ion intensities using a machine-learning approach that estimates the likelihood of observed intensities given peptide and fragment attributes. From 1,000,000 spectra, we chose 27,000 with high-quality, nonredundant matches as training data. Using the same 27,000 spectra, intensity was similarly modeled with mismatched peptides. We used these two probabilistic models to compute the relative likelihood of an observed spectrum given that a candidate peptide is matched or mismatched. We used a 'decoy' proteome approach to estimate incorrect match frequency, and demonstrated that an intensity-based method reduces peptide identification error by 50-96% without any loss in sensitivity.

Algorithms↗

Learning multiple evolutionary pathways from cross-sectional data.

We introduce a mixture model of trees to describe evolutionary processes that are characterized by the ordered accumulation of permanent genetic changes. The basic building block of the model is a directed weighted tree that generates a probability distribution on the set of all patterns of genetic events. We present an EM-like algorithm for learning a mixture model of K trees and show how to determine K with a maximum likelihood approach. As a case study, we consider the accumulation of mutations in the HIV-1 reverse transcriptase that are associated with drug resistance. The fitted model is statistically validated as a density estimator, and the stability of the model topology is analyzed. We obtain a generative probabilistic model for the development of drug resistance in HIV that agrees with biological knowledge. Further applications and extensions of the model are discussed.

Algorithms↗

Mtreemix: a software package for learning and using mixture models of mutagenetic trees.

SUMMARY: Mixture models of mutagenetic trees constitute a class of probabilistic models for describing evolutionary processes that are characterized by the accumulation of permanent genetic changes. They have been applied to model the accumulation of chromosomal gains and losses in tumor development and the development of drug resistance-associated mutations in the HIV genome.Mtreemix is a software package for estimating mutagenetic trees mixture models from observed cross-sectional data and for using these models for predictions. We provide programs for model fitting, model selection, simulation, likelihood computation and waiting time estimation. AVAILABILITY: Mtreemix, including source code, documentation, sample data files and precompiled Solaris and Linux binaries, is freely available for non-commercial users at http://mtreemix.bioinf.mpi-sb.mpg.de/

Algorithms↗

Improved model for specimen classification based on single-cell classifiers.

We consider probabilistic models for specimen classification procedures based on systems which classify individual cells as normal or abnormal. The models which we consider generalize those discussed previously by Castleman and White (Anal. Quant. Cytol. 2:117-122, 1980; Cytometry 2:155-158, 1981) and by Timmers and Gelsema (Cytometry 6:22-25, 1985). In particular, they include the biologically plausible possibility that the specimen contains cells which are intermediate between the extremes of normal and abnormal. We find that if these additional cells occur differentially in normal and abnormal specimens, then specimen classification can become substantially more efficient when the cell classifier has different error rates for these cells.

Cervix Uteri↗

A simple model of the thermal prebiotic oligomerization of amino acids.

We construct a probabilistic model with the aid of the Markov chain formalism to describe and give a physico-chemical justification to an oligomerization process of a set of amino acids under certain prebiotic conditions. Such chemical process shows a remarkable bias in the polymer products that our model can explain. Some predictions and limitations are also discussed.

Amino Acids↗

A model of aging and a shape of the observed force of mortality.

A probabilistic model of aging is considered. It is based on the assumption that a random resource, a stochastic process of aging (wear) and the corresponding anti-aging process are embedded at birth. A death occurs when the accumulated wear exceeds the initial random resource. It is assumed that the anti-aging process decreases wear in each increment. The impact of environment (lifestyle) is also taken into account. The corresponding relations for the observed and the conditional hazard rate (force of mortality) are obtained. Similar to some demographic models, the deceleration of mortality phenomenon is explained via the concept of frailty. Simple examples are considered.

Aged↗