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The probability heuristics model of syllogistic reasoning.

A probability heuristic model (PHM) for syllogistic reasoning is proposed. An informational ordering over quantified statements suggests simple probability based heuristics for syllogistic reasoning. The most important is the "min-heuristic": choose the type of the least informative premise as the type of the conclusion. The rationality of this heuristic is confirmed by an analysis of the probabilistic validity of syllogistic reasoning which treats logical inference as a limiting case of probabilistic inference. A meta-analysis of past experiments reveals close fits with PHM. PHM also compares favorably with alternative accounts, including mental logics, mental models, and deduction as verbal reasoning. Crucially, PHM extends naturally to generalized quantifiers, such as Most and Few, which have not been characterized logically and are, consequently, beyond the scope of current mental logic and mental model theories. Two experiments confirm the novel predictions of PHM when generalized quantifiers are used in syllogistic arguments. PHM suggests that syllogistic reasoning performance may be determined by simple but rational informational strategies justified by probability theory rather than by logic.

Algorithms↗

Risk-based modeling of early warning systems for pollution accidents.

An early warning system is a mechanism for detecting, characterizing and providing notification of a source water contamination event (spill event) in order to mitigate the impact of contamination. Spill events are highly probabilistic occurrences with major spills, which can have very significant impacts on raw water sources of drinking water, being relatively rare. A systematic method for designing and operating early warning systems that considers the highly variable, probabilistic nature of many aspects of the system is described. The methodology accounts for the probability of spills, behavior of monitoring equipment, variable hydrology, and the probability of obtaining information about spills independent of a monitoring system. Spill Risk, a risk-based model using Monte Carlo simulation techniques has been developed and its utility has been demonstrated as part of an AWWA Research Foundation sponsored project. The model has been applied to several hypothetical river situations and to an actual section of the Ohio River. Additionally, the model has been systematically applied to a wide range of conditions in order to develop general guidance on design of early warning systems.

Accidents↗

Prediction of splice sites with dependency graphs and their expanded bayesian networks.

MOTIVATION: Owing to the complete sequencing of human and many other genomes, huge amounts of DNA sequence data have been accumulated. In bioinformatics, an important issue is how to predict the complete structure of genes from the genomic DNA sequence, especially the human genome. A crucial part in the gene structure prediction is to determine the precise exon-intron boundaries, i.e. the splice sites, in the coding region. RESULTS: We have developed a dependency graph model to fully capture the intrinsic interdependency between base positions in a splice site. The establishment of dependency between two position is based on a chi2-test from known sample data. To facilitate statistical inference, we have expanded the dependency graph (which is usually a graph with cycles that make probabilistic reasoning very difficult, if not impossible) into a Bayesian network (which is a directed acyclic graph that facilitates statistical reasoning). When compared with the existing models such as weight matrix model, weight array model, maximal dependence decomposition, Cai et al.'s tree model as well as the less-studied second-order and third-order Markov chain models, the expanded Bayesian networks from our dependency graph models perform the best in nearly all the cases studied. AVAILABILITY: Software (a program called DGSplicer) and datasets used are available at http://csrl.ee.nthu.edu.tw/bioinf/ CONTACT: cclu@ee.nthu.edu.tw.

Bayes Theorem↗

Validation of probabilistic predictions.

Current advances in high-speed computing and increased availability of statistical software have led to widespread use of statistical methods for the development of computerized protocols predictive of binary health outcomes. If these predictive algorithms are to be used in settings other than those for which they were developed, e.g., applied in a different geographic setting or extrapolated for use in a slightly different population, then they should be carefully validated to ensure appropriate application. Miller et al. (Stat Med. 1991) provided a comprehensive methodology for external validation of logistic prediction models, and applied these methods in a temporal validation setting. In this article, the authors emphasize how these methods can be applied to general forms of probabilistic predictions and provide several SAS macros for computation of the desired statistics.

Adolescent↗

Performance of threading scoring functions designed using new optimization method.

We present a new procedure for optimization of a threading scoring function. A scoring function is usually formulated in terms of the structural environment states that describe the protein fold model. We propose a method for the optimal selection of those structural environment states that naturally follows from the probabilistic description of the threading problem and is done prior to threading experiments. We demonstrate the selection of the optimal structural environment states for the solvent exposure of the amino acid position, and present the results of threading experiments performed using scoring functions designed with and without the optimization of the structural environment states. These results confirm that the optimal scoring function predicts the sequence-to-structure alignments most accurately. Threading experiments performed with 15 optimally designed scoring functions show that the correlation coefficient between the information content of the amino acid distribution that determines the scoring function and the accuracy of the optimal sequence-to-structure alignment is 0.94.

Amino Acid Sequence↗

Markov random field modeling in posteroanterior chest radiograph segmentation.

Previously, the authors presented an algorithm that identifies lung regions in a digitized posteroanterior chest radiograph (DCR) by labeling each pixel as either lung or nonlung. In this manuscript, the inherent flexibility of this algorithm is demonstrated as the algorithm is generalized to identify multiple anatomical regions in a DCR. Specifically, each pixel is classified as belonging to one of six anatomical region types: lung, subdiaphragm, heart, mediastinum, body, or background. The algorithm determines the optimal set of pixel classifications, xOPT, for a given set of DCR pixel gray level values y via a probabilistic approach that defines xOPT as the particular segmentation that maximizes the conditional distribution P(x/y). A spatially varying Markov random field (MRF) model is used that incorporates spatial and textural information of each possible region type. MRF modeling provides the form of P(x/y), and Iterated Conditional Modes is used to converge to the distribution maximum of P(x/y) thus obtaining the optimal segmentation for a given DCR. Results show the algorithm being able to correctly classify 90.0% +/- 3.4% of the pixels in a DCR.

Algorithms↗

Performance assessments of nuclear waste repositories: a dialogue on their value and limitations.

Performance Assessment (PA) is the use of mathematical models to simulate the long-term behavior of engineered and geologic barriers in a nuclear waste repository; methods of uncertainty analysis are used to assess effects of parametric and conceptual uncertainties associated with the model system upon the uncertainty in outcomes of the simulation. PA is required by the U.S. Environmental Protection Agency as part of its certification process for geologic repositories for nuclear waste. This paper is a dialogue to explore the value and limitations of PA. Two "skeptics" acknowledge the utility of PA in organizing the scientific investigations that are necessary for confident siting and licensing of a repository; however, they maintain that the PA process, at least as it is currently implemented, is an essentially unscientific process with shortcomings that may provide results of limited use in evaluating actual effects on public health and safety. Conceptual uncertainties in a PA analysis can be so great that results can be confidently applied only over short time ranges, the antithesis of the purpose behind long-term, geologic disposal. Two "proponents" of PA agree that performance assessment is unscientific, but only in the sense that PA is an engineering analysis that uses existing scientific knowledge to support public policy decisions, rather than an investigation intended to increase fundamental knowledge of nature; PA has different goals and constraints than a typical scientific study. The "proponents" describe an ideal, six-step process for conducting generalized PA, here called probabilistic systems analysis (PSA); they note that virtually all scientific content of a PA is introduced during the model-building steps of a PSA; they contend that a PA based on simple but scientifically acceptable mathematical models can provide useful and objective input to regulatory decision makers. The value of the results of any PA must lie between these two views and will depend on the level of knowledge of the site, the degree to which models capture actual physical and chemical processes, the time over which extrapolations are made, and the proper evaluation of health risks attending implementation of the repository. The challenge is in evaluating whether the quality of the PA matches the needs of decision makers charged with protecting the health and safety of the public.

Geological Phenomena↗

On some formulas in a partnership model from the perspective of a semi-Markov process.

Many deterministic models of sexually transmitted diseases, as well as population models in general, contain elements of stochastic or statistical reasoning. An example of such a model is that of Dietz and Hadeler (1988) concerning sexually transmitted diseases in which there is partnership formation and dissolution. Among the interesting formulas in this paper, which enter into the analysis of the model, are those for the expected number of partners a male or female has during a lifetime. To a probabilist such formulas suggest the possibility that some stochastic process may be constructed so as to yield these formulas as well as others that may be of interest. The principal purpose of this paper is to demonstrate that such a stochastic process does indeed exist in the form of a three state semi-Markov process in continuous time with stationary laws of evolution and with a one-step density matrix determined by four parameters which were interpreted as constant latent risk functions in the classical theory of competing risks. This construction of a semi-Markov process not only provides a framework for the systematic derivation of the formulas of Dietz and Hadeler but also suggests pathways for extensions to the age-dependent case.

Female↗

External control in Markovian genetic regulatory networks: the imperfect information case.

Probabilistic Boolean Networks, which form a subclass of Markovian Genetic Regulatory Networks, have been recently introduced as a rule-based paradigm for modeling gene regulatory networks. In an earlier paper, we introduced external control into Markovian Genetic Regulatory networks. More precisely, given a Markovian genetic regulatory network whose state transition probabilities depend on an external (control) variable, a Dynamic Programming-based procedure was developed by which one could choose the sequence of control actions that minimized a given performance index over a finite number of steps. The control algorithm of that paper, however, could be implemented only when one had perfect knowledge of the states of the Markov Chain. This paper presents a control strategy that can be implemented in the imperfect information case, and makes use of the available measurements which are assumed to be probabilistically related to the states of the underlying Markov Chain.

Algorithms↗

Mapping protein energy landscapes with amide hydrogen exchange and mass spectrometry: I. A generalized model for a two-state protein and comparison with experiment.

Protein amide hydrogen exchange (HDX) is a convoluted process, whose kinetics is determined by both dynamics of the protein and the intrinsic exchange rate of labile hydrogen atoms fully exposed to solvent. Both processes are influenced by a variety of intrinsic and extrinsic factors. A mathematical formalism initially developed to rationalize exchange kinetics of individual amide hydrogen atoms is now often used to interpret global exchange kinetics (e.g., as measured in HDX MS experiments). One particularly important advantage of HDX MS is direct visualization of various protein states by observing distinct protein ion populations with different levels of isotope labeling under conditions favoring correlated exchange (the so-called EX1 exchange mechanism). However, mildly denaturing conditions often lead to a situation where the overall HDX kinetics cannot be clearly classified as either EX1 or EX2. The goal of this work is to develop a framework for a generalized exchange model that takes into account multiple processes leading to amide hydrogen exchange, and does not require that the exchange proceed strictly via EX1 or EX2 kinetics. To achieve this goal, we use a probabilistic approach that assigns a transition probability and a residual protection to each equilibrium state of the protein. When applied to a small protein chymotrypsin inhibitor 2, the algorithm allows complex HDX patterns observed experimentally to be modeled with remarkably good fidelity. On the basis of the model we are now in a position to begin to extract quantitative dynamic information from convoluted exchange kinetics.

Algorithms↗

Probabilistic methods in BCI research.

This paper suggests a probabilistic treatment of the signal processing part of a brain-computer interface (BCI). We suggest two improvements for BCIs that cannot be obtained easily with other data driven approaches. Simply by using one large joint distribution as a model of the entire signal processing part of the BCI, we can obtain predictions that implicitly weight information according to its certainty. Offline experiments reveal that this results in statistically significant higher bit rates. Probabilistic methods are also very useful to obtain adaptive learning algorithms that can cope with nonstationary problems. An experimental evaluation shows that an adaptive BCI outperforms the equivalent static implementations, even when using only a moderate number of trials. This suggests that adaptive translation algorithms might help in cases where brain dynamics change due to learning effects or fatigue.

Algorithms↗

Dynamical model of signal propagation in the heart.

We present a simple model, describing the propagation of a travelling signal in a media that is intended to model phenomena in cardiac tissue. The model is a caricature designed to examine some characteristics of a propagating medium that can support spontaneous and non-stimulated fibrillation behaviour. The model consists of a large number of weakly interacting components, each of which operates according to a simplified set of rules. Specifically it is a form of cellular automaton, with the introduction of probabilistic nature in terms of a random refractory period.

Computer Simulation↗

DT-Planner: an environment for managing dynamic decision problems.

The problem of formulating plans under uncertainty and coping with dynamic decision problems is a major task of both artificial intelligence and control theory applications in medicine. In this paper we will describe a software package, called DT-Planner, designed to represent and solve dynamic decision problems that can be modelled as Markov decision processes, by exploiting a novel graphical formalism, called influence view. An influence view is a directed acyclic graph that depicts the probabilistic relationships between the problem state variables in a generic time transition; additional variables, called event variables, may be added, in order to describe the conditional independencies between state variables. By using the specified conditional independence structure, an influence view may allow a parsimonious specification of a Markov decision process. DT-Planner lets the user specify and manage models through a user-friendly graphical interface, and implements efficient for policy determination algorithms. DT-Planner is written in C with Open Interface libraries and can be obtained, for non commercial use, via anonymous ftp without charge.

Algorithms↗

Segmentation of brain tumors in 4D MR images using the hidden Markov model.

Tumor size is an objective measure that is used to evaluate the effectiveness of anticancer agents. Responses to therapy are categorized as complete response, partial response, stable disease and progressive disease. Implicit in this scheme is the change in the tumor over time; however, most tumor segmentation algorithms do not use temporal information. Here we introduce an automated method using probabilistic reasoning over both space and time to segment brain tumors from 4D spatio-temporal MRI data. The 3D expectation-maximization method is extended using the hidden Markov model to infer tumor classification based on previous and subsequent segmentation results. Spatial coherence via a Markov Random Field was included in the 3D spatial model. Simulated images as well as patient images from three independent sources were used to validate this method. The sensitivity and specificity of tumor segmentation using this spatio-temporal model is improved over commonly used spatial or temporal models alone.

Brain Neoplasms↗

Novel probabilistic method for precisely correcting the QT interval for heart rate in telemetered dogs and cynomolgus monkeys.

INTRODUCTION: QT intervals are not regulated on a beat-to-beat cadence, but are strongly influenced by the preceding heart rate history (hysteresis). ECG sampling, when performed over sufficiently long periods, results in the detection of ranges of different QT values for each discrete RR interval. Given the potential impact of QT hysteresis in QT interval rate-correction procedures, we hypothesized that, physiologically, the QT interval exists as a probabilistic variable where the exact value corresponding to any RR interval is precisely estimated from the associated QT population. METHODS: Digital ECGs were collected for 18-21 h in telemetered dogs (n=7) and cynomolgus monkeys (n=7) employing epicardial ECG leads for accurate T(end) detection, and analyzed by computerized algorithms. Descriptive statistics were calculated for raw QT values in 10 ms RR increments. Individual rate-corrected QT (QTc) formulae were derived from the slopes of log-transformed QT-RR data where each QT point was the mean of >250 beats/RR increment. The aptness of this QTc model was assessed by residual analysis. RESULTS: Beat-to-beat ECG analysis demonstrated that for all discrete cycle lengths, the associated raw QT intervals were normally distributed populations, spanning approximately 30-40 and 45-100 ms in the dog and cynomolgus monkey, respectively. In both species, QTc was stable (< or =5 ms variation) over all physiological RR intervals. DISCUSSION: The probabilistic treatment of raw QT interval populations natively associated to any RR interval provides hysteresis-free raw QT estimates which can be accurately modeled, allowing the derivation of a precise QTc value. Previous unawareness of the probabilistic nature of the QT interval explains the historical failure of numerous QT rate-correction formulae to correctly solve this scientific issue. Importantly, QT distribution analysis has the potential to provide, for the first time, a universal and sensitive method for QT heart rate-correction, providing a robust method for nonclinical and clinical cardiac safety investigations of repolarization delay.

Algorithms↗

Mining functional modules in genetic networks with decomposable graphical models.

In recent years, graphical models have become an increasingly important tool for the structural analysis of genome-wide expression profiles at the systems level. Here we present a new graphical modelling technique, which is based on decomposable graphical models, and apply it to a set of gene expression profiles from acute lymphoblastic leukemia (ALL). The new method explains probabilistic dependencies of expression levels in terms of the concerted action of underlying genetic functional modules, which are represented as so-called "cliques" in the graph. In addition, the method uses continuous-valued (instead of discretized) expression levels, and makes no particular assumption about their probability distribution. We show that the method successfully groups members of known functional modules to cliques. Our method allows the evaluation of the importance of genes for global cellular functions based on both link count and the clique membership count.

Gene Expression Profiling↗

Computer simulation of growth of anastomosing microvascular networks.

Stochastic growth of polygonal microvascular networks was simulated on computer by dichotomous terminal branching and bridging (anastomosing with an existing segment). The model was applied to describe microvascular growth into a rectangular plane from the sides when vessels bifurcate in a probabilistic manner. The angle of bifurcation was drawn from a normal distribution, the mean of which was varied between 40 degrees and 80 degrees. The resulting networks contained an average of 88-104 nodes of which 30-38% were due to bridging. Number of nodes, number of branches, number of vascular polygons and a fractal dimension representing the density of nodes were calculated for each simulated network. Capillary density increased when mean angle of bifurcation was increased between 40 degrees and 80 degrees. Distributions of normalized vessel lengths and polygon shapes were compared with those of a mesenteric vascular network. The distributions were not found to be significantly different (p less than 0.05) for most values of the mean angle of bifurcation, matching best for the mean bifurcation angle of 50 degrees. Vascular polygons had an average shape between pentagonal and hexagonal for the mesenteric network as well as for all values of the mean bifurcation angle used in this study.

Capillaries↗

Prediction error as a linear function of reward probability is coded in human nucleus accumbens.

Reward probability has been shown to be coded by dopamine neurons in monkeys. Phasic neuronal activation not only increased linearly with reward probability upon expectation of reward, but also varied monotonically across the range of probabilities upon omission or receipt of rewards, therefore modeling discrepancies between expected and received rewards. Such a discrete coding of prediction error has been suggested to be one of the basic principles of learning. We used functional magnetic resonance imaging (fMRI) to show that the human dopamine system codes reward probability and prediction error in a similar way. We used a simple delayed incentive task with a discrete range of reward probabilities from 0%-100%. Activity in the nucleus accumbens of human subjects strongly resembled the phasic responses found in monkey neurons. First, during the expectation period of the task, the fMRI signal in the human nucleus accumbens (NAc) increased linearly with the probability of the reward. Second, during the outcome phase, activity in the NAc coded the prediction error as a linear function of reward probabilities. Third, we found that the Nac signal was correlated with individual differences in sensation seeking and novelty seeking, indicating a link between individual fMRI activation of the dopamine system in a probabilistic paradigm and personality traits previously suggested to be linked with reward processing. We therefore identify two different covariates that model activity in the Nac: specific properties of a psychological task and individual character traits.

Adult↗