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PubMed2001

Variations on probabilistic suffix trees: statistical modeling and prediction of protein families.

MOTIVATION: We present a method for modeling protein families by means of probabilistic suffix trees (PSTs). The method is based on identifying significant patterns in a set of related protein sequences. The patterns can be of arbitrary length, and the input sequences do not need to be aligned, nor is delineation of domain boundaries required. The method is automatic, and can be applied, without assuming any preliminary biological information, with surprising success. Basic biological considerations such as amino acid background probabilities, and amino acids substitution probabilities can be incorporated to improve performance. RESULTS: The PST can serve as a predictive tool for protein sequence classification, and for detecting conserved patterns (possibly functionally or structurally important) within protein sequences. The method was tested on the Pfam database of protein families with more than satisfactory performance. Exhaustive evaluations show that the PST model detects much more related sequences than pairwise methods such as Gapped-BLAST, and is almost as sensitive as a hidden Markov model that is trained from a multiple alignment of the input sequences, while being much faster.

Algorithms↗
PubMedDate not supplied

Information flow, expectations and job search: rural-to-urban migration process in India.

"Probabilistic migration models assume that search for urban jobs is entirely an urban-based activity and that employment in free-entry activities is a transitional phase during which migrants are actively searching for formal sector employment. This paper tests the empirical validity of these assumptions using data, collected by the author in a sample survey in Delhi [India] in 1975-76, on 1,400 migrants from rural areas." Evidence is presented "that the migration process postulated in probabilistic models is not realistic in the case of Delhi. Over one-half of the sample had moved to Delhi after lining up specific jobs; a sizeable proportion expected to enter on arrival activities generally considered to be characterized by freedom of entry; and the majority of entrants into free-activities did not search for alternative employment and were engaged in the same activities at the time of the survey."

Asia↗
PubMed2025

Novel Predictive Spatial Biomarker in Non-Small Cell Lung Carcinoma: The Diversity of Niches Unlocking Treatment Sensitivity (DONUTS).

Probabilistic spatial modelling techniques developed on large-scale tumor-immune Atlases (~35M individually mapped cells; 50,000 high power fields) were used to characterize predictive features of treatment-responsive lung cancer. We identified CD8+FoxP3+ cell density as a robust pre-treatment biomarker for outcomes across disease stages and therapy types. In parallel, single-cell RNAseq studies of CD8+FoxP3+ T-cells revealed an activated, early effector phenotype, substantiating an anti-tumor role, and contrasting with CD4+FoxP3+ T-regulatory cells. A spatial biomarker was developed using an empirical probabilistic model to define the immediate cell neighbors or niche surrounding CD8+FoxP3+ cells and proximity to the tumor-stromal boundary. The resultant 'Diversity of Niches Unlocking Treatment Sensitivity (DONUTS)' are more prevalent than the CD8+FoxP3+ cells themselves, mitigating sampling error in small biopsies. Further, the DONUTS only require four markers, are additive to PD-L1, and associate with tertiary lymphoid structure counts. Taken together, the DONUTS represent a next-generation predictive biomarker poised for clinical implementation.

AstroPath↗
PubMed2002

Probabilistic fasteners with parabolic elements: biological system, artificial model and theoretical considerations.

Probabilistic fasteners are attachment devices composed of two surfaces covered with cuticular micro-outgrowths. Friction-based fasteners demonstrate high frictional forces when the surfaces come into contact. Attachment in this case is based on the use of the surface profile and mechanical properties of materials, and is fast, precise and reversible. The best-studied examples composed of parabolic elements are the wing-locking mechanism in beetles and the head arrester in dragonflies. This study combines experimental data of force measurements, obtained in an artificial model system, and theoretical considerations based on the simple model of behaviour of probabilistic fasteners with parabolic elements. Elements of the geometry in both cases correspond to the biological prototypes. Force measurements on the artificial system show that the attachment force is strongly dependent on the load force. At small loads, the increase of attachment is very slow, whereas rapid increase of attachment was detected at higher loads. At very high loads, a saturation of the attachment force was revealed. A simple explanation of the attachment principle is that with an increasing load elements of both surfaces slide into gaps of the corresponding part. This results in an increase of lateral loading forces acting on elements. High lateral forces lead to an increase of friction between single sliding elements. An analytical model which describes behaviour of the probabilistic fasteners with parabolic elements is proposed.

Animals↗
PubMed2005

Decision-analytical model with lifetime estimation of costs and health outcomes for one-time screening for abdominal aortic aneurysm in 65-year-old men.

BACKGROUND: Abdominal aortic aneurysm (AAA) causes about 2 per cent of all deaths in men over the age of 65 years. A major improvement in operative mortality would have little impact on total mortality, so screening for AAA has been recommended as a solution. The cost-effectiveness of a programme that invited 65-year-old men for ultrasonographic screening was compared with current clinical practice in a decision-analytical model. METHODS: In a probabilistic Markov model, costs and health outcomes of a screening programme and current clinical practice were simulated over a lifetime perspective. To populate the model with the best available evidence, data from published papers, vascular databases and primary research were used. RESULTS: The results of the base-case analysis showed that the incremental cost per gained life-year for a screening programme compared with current practice was 7760, and that for a quality-adjusted life-year was 9700. The probability of screening being cost-effective was high. CONCLUSION: A financially and practically feasible screening programme for AAA, in which men are invited for ultrasonography in the year in which they turn 65, appears to yield positive health outcomes at a reasonable cost.

Aged↗
PubMed2003

Measures of importance for economic analysis based on decision modeling.

In probabilistic economic analysis, the uncertainty concerning input parameters is quantified, and determines the level of uncertainty over the optimal decision. Researchers from a wide range of disciplines employ mathematical models to simulate complex processes. Common through many such disciplines is the conduct of importance analysis to determine those input parameters that contribute most to the uncertainty over the optimal decision based on the results of the analysis. In this study, we compare a range of potential importance measures to see how they compare with methods used in economic analysis. Techniques were classified as variance/correlation, information, probability, entropy, or elasticity-based measures. A selection of the most commonly used measures were applied to an economic model of treatment for patients with Parkinson's disease. Techniques were evaluated in terms of their ranking of variables, complexity, and interpretation.

Cost-Benefit Analysis↗
PubMed2007

Computation of likelihood ratios in fingerprint identification for configurations of any number of minutiae.

Recent court challenges have highlighted the need for statistical research on fingerprint identification. This paper proposes a model for computing likelihood ratios (LRs) to assess the evidential value of comparisons with any number of minutiae. The model considers minutiae type, direction and relative spatial relationships. It expands on previous work on three minutiae by adopting a spatial modeling using radial triangulation and a probabilistic distortion model for assessing the numerator of the LR. The model has been tested on a sample of 686 ulnar loops and 204 arches. Features vectors used for statistical analysis have been obtained following a preprocessing step based on Gabor filtering and image processing to extract minutiae data. The metric used to assess similarity between two feature vectors is based on an Euclidean distance measure. Tippett plots and rates of misleading evidence have been used as performance indicators of the model. The model has shown encouraging behavior with low rates of misleading evidence and a LR power of the model increasing significantly with the number of minutiae. The LRs that it provides are highly indicative of identity of source on a significant proportion of cases, even when considering configurations with few minutiae. In contrast with previous research, the model, in addition to minutia type and direction, incorporates spatial relationships of minutiae without introducing probabilistic independence assumptions. The model also accounts for finger distortion.

Dermatoglyphics↗
PubMed1999

Using probabilistic neural networks to model the toxicity of chemicals to the fathead minnow (Pimephales promelas): a study based on 865 compounds.

We investigate the use of probabilistic neural networks (PNN) to model the acute toxicity (96-hr LC50) to the fathead minnow (Pimephales promelas) based on a 865 chemicals data set. In contrast to most other toxicological models, the octanol/water partition coefficient is not used as input parameter. The information fed into the neural network is solely based on simple molecular descriptors as can be derived from the chemicals' structures and indicates the potential of this approach as general methodology for the estimation of toxicological effects of chemicals.

Animals↗
PubMed2005

Human microRNA prediction through a probabilistic co-learning model of sequence and structure.

MicroRNAs (miRNAs) are small regulatory RNAs of approximately 22 nt. Although hundreds of miRNAs have been identified through experimental complementary DNA cloning methods and computational efforts, previous approaches could detect only abundantly expressed miRNAs or close homologs of previously identified miRNAs. Here, we introduce a probabilistic co-learning model for miRNA gene finding, ProMiR, which simultaneously considers the structure and sequence of miRNA precursors (pre-miRNAs). On 5-fold cross-validation with 136 referenced human datasets, the efficiency of the classification shows 73% sensitivity and 96% specificity. When applied to genome screening for novel miRNAs on human chromosomes 16, 17, 18 and 19, ProMiR effectively searches distantly homologous patterns over diverse pre-miRNAs, detecting at least 23 novel miRNA gene candidates. Importantly, the miRNA gene candidates do not demonstrate clear sequence similarity to the known miRNA genes. By quantitative PCR followed by RNA interference against Drosha, we experimentally confirmed that 9 of the 23 representative candidate genes express transcripts that are processed by the miRNA biogenesis enzyme Drosha in HeLa cells, indicating that ProMiR may successfully predict miRNA genes with at least 40% accuracy. Our study suggests that the miRNA gene family may be more abundant than previously anticipated, and confer highly extensive regulatory networks on eukaryotic cells.

Algorithms↗
PubMed1992

Covariation in natural causal induction.

The covariation component of everyday causal inference has been depicted, in both cognitive and social psychology as well as in philosophy, as heterogeneous and prone to biases. The models and biases discussed in these domains are analyzed with respect to focal sets: contextually determined sets of events over which covariation is computed. Moreover, these models are compared to our probabilistic contrast model, which specifies causes as first and higher order contrasts computed over events in a focal set. Contrary to the previous depiction of covariation computation, the present assessment indicates that a single normative mechanism--the computation of probabilistic contrasts--underlies this essential component of natural causal induction both in everyday and in scientific situations.

Cognition↗
PubMed1993

Probabilistic constraint satisfaction with structural models: application to organ modeling by radial contours.

One of the key challenges within medical information sciences is the development of useful models for biological structure and its variability. Many biomedical problems involve the elucidation of structure (for example, from experimental data or from imaging studies), and structural models can often drive the process of inferring precise structure from data. Ideally, model-driven data interpretation combines knowledge about the generic features of a class of biological structures (as contained within a model) with data that provide specific information (often noisy) about a particular instance of the class. In this paper we briefly discuss model-driven determination of biological structure as an example of a structural constraint satisfaction problem. We describe a probabilistic implementation of structural constraint satisfaction, and show that our formulation of a particular organ modeling technology (Radial Contour Models) exhibits promising performance. Our results demonstrate the utility of probabilistic models for the solution of structural constraint satisfaction problems.

Computer Simulation↗
PubMed2004

Uro-gramma: the importance of updating the predictive model.

OBJECTIVES: Uro-gramma is a probabilistic predictive model of pathological staging of prostate cancer (Pca) from preoperative parameters (PSA, clinical Gs, clinical stage) published in 2000. Aim of this study is to improve Uro-gramma, updating it, to take into account the continuous evolution of the population. MATERIALS AND METHODS: From 1998 to 2000, 991 Pca patients have undergone radical prostatectomy in several Italian urological centers. Inclusion criteria were: preoperative PSA < 50 ng/ml, clinical stage < or = T3c, availability of a bioptic Gs and pathological staging. A predictive model has been estimated for each year and its behaviour on the following years tested, using Hosmer and Lemeshow tests, which compare the expected rate with the observed one. RESULTS: The mean age was 66.3 years. Pca familiarity was present in 3.2% of the patients in 1998, 2.6% in 1999 and 7.4% in 2000. PSA values < 10 have increased (from 41% to 47%) and those > 10 decreased (from 59% to 53%). The mean number of bioptic samples per patient has increased from 4.9 to 6, while clinical and pathologic Gs have remained stable. An increase in the rate of organ confined Pca has been noticed, either clinically (87.4% in 1998, 92% in 2000) or pathologically (55.2% in '98, 57% in 2000). Staging lymphadenectomy has been performed in 88% of the pts in 1998, 94.2% in 1999 and 94.5% in 2000, whereas the % of N+ patients has moved from 11.3% in 1998 to 9.8% in 2000. CONCLUSIONS: Uro-gramma update results show that the mean estimate error has fallen from 6.4% to 1.2%. The new model strengthens the previous one and confirms its validity, but it also underlines the need of a constant update to take into account the continuous evolution of the population and of the methods of diagnosis and staging.

Aged↗
PubMed1997

Transition probability cell cycle model. Part I--Balanced growth.

A cell cycle model based on the concept of a transition probability first proposed by Smith & Martin has been implemented as a differential equation model. The probabilistic A-state is modeled as a lumped parameter while the deterministic B-phase is modeled as a distributed parameter, and analytical solutions for both the population and the fraction of labeled mitosis (FLM) curves are derived under balanced growth conditions. Contributions toward cell cycle variability by single and double random transitions are considered. A double transition model provides a more realistic description of the cell cycle time distribution. For gross cell population behavior, a single transition from the A-state to the B-phase may provide acceptable approximation. In spite of the simplification, the single transition Smith & Martin model is shown to describe the gradual asynchronization of a cell population.

Animals↗
PubMed2000

Wide-coverage probabilistic sentence processing.

This paper describes a fully implemented, broad-coverage model of human syntactic processing. The model uses probabilistic parsing techniques, which combine phrase structure, lexical category, and limited subcategory probabilities with an incremental, left-to-right "pruning" mechanism based on cascaded Markov models. The parameters of the system are established through a uniform training algorithm, which determines maximum-likelihood estimates from a parsed corpus. The probabilistic parsing mechanism enables the system to achieve good accuracy on typical, "garden-variety" language (i.e., when tested on corpora). Furthermore, the incremental probabilistic ranking of the preferred analyses during parsing also naturally explains observed human behavior for a range of garden-path structures. We do not make strong psychological claims about the specific probabilistic mechanism discussed here, which is limited by a number of practical considerations. Rather, we argue incremental probabilistic parsing models are, in general, extremely well suited to explaining this dual nature--generally good and occasionally pathological--of human linguistic performance.

Cognition↗
PubMed2002

Analysis of solvent central nervous system toxicity and ethanol interactions using a human population physiologically based kinetic and dynamic model.

The effect of acute ethanol-mediated inhibition of m-xylene metabolism on central nervous system (CNS) depression in the human worker population was investigated using physiologically based pharmacokinetic (PBPK) models and probabilistic random (Monte Carlo) sampling. PBPK models of inhaled m-xylene and orally ingested ethanol were developed and combined by a competitive enzyme (CYP2E1) inhibition model. Human interindividual variability was modeled by combining estimated statistical distributions of model parameters with the deterministic PBPK models and multiple random or Monte Carlo simulations. A simple threshold pharmacodynamic model was obtained by simulating m-xylene kinetics in human studies where CNS effects were observed and assigning the peak venous blood m-xylene concentration (C(V,max)) as the dose surrogate of toxicity. Probabilistic estimates of an individual experiencing CNS disturbances given exposure to the current UK occupational exposure standard (100 ppm time-weighted average over 8 h), with and without ethanol ingestion, were obtained. The probability of experiencing CNS effects given this scenario increases markedly and nonlinearly with ethanol dose. As CYP2E1-mediated metabolism of other occupationally relevant organic compounds may be inhibited by ethanol, simulation studies of this type should have an increasingly significant role in the chemical toxicity risk assessment.

Administration, Oral↗
PubMed2000

Is causal induction based on causal power? Critique of Cheng (1997).

The authors empirically evaluate P. W. Cheng's (1997) power PC theory of causal induction. They reanalyze some published data taken to support the theory and show instead that the data are at variance with it. Then, they report 6 experiments in which participants evaluated the causal relationship between a fictitious chemical and DNA mutations. The power PC theory assumes that participants' estimates are based on the causal power p of a potential cause, where p is the contingency between the cause and the effect normalized by the base rate of the effect. Three of the experiments used a procedure in which causal information was presented trial by trial. For these experiments, the power PC theory was contrasted with the predictions of the probabilistic contrast model and the Rescorla-Wagner theory. For the remaining 3 experiments, a summary presentation format was employed to which only the probabilistic contrast model and the power PC theory are applicable. The power PC theory was unequivocally contradicted by the results obtained in these experiments, whereas the other 2 theories proved to be satisfactory.

Adult↗
PubMed1980

Extant models of the psychophysical function: a comparison.

Previous research has tested the efficacy of the deterministic-sensory model versus probabilistic-sensory-learning model for psychophysical relationships when cognitive factors were manipulated. The present study attempted to expand those findings by holding cognitive factors constant and varying a perceptual factor within a stimulus class. Subjects made magnitude estimations of skin-area contact for each of two sets of weights which varied identically in surface area but different in that one set also varied in accelerative force whereas the other did not. A power function was obtained only for that set which varied with respect to accelerative force, supporting the deterministic-sensory model. These results are consistent with those of electro-physiological studies which have related transducer activity to the dynamic component of a mechanical stimulus. It was suggested that better conceptualization of "cognitive" and "perceptual" factors is needed before further research in this area is undertaken.

Adolescent↗
PubMedDate not supplied

Estimating human exposure to selected motor vehicle pollutants using the NEM series of models: lessons to be learned.

This paper reviews the use of exposure modeling by the Ambient Standards Branch (ASB) of EPA's Office of Air Quality Planning and Standards. The Branch uses exposure assessments to evaluate health risks associated with attainment of alternative National Ambient Air Quality Standards (NAAQS). This paper examines the history of the NAAQS Exposure Model (NEM) and probabilistic NEM (pNEM) models and the role that they have played in NAAQS reviews of lead, carbon monoxide, nitrogen dioxide, and oxygen. Trends in how the following substantive issues were addressed in the NEM series of models are reviewed: (1) exposure and dose metrics; (2) microenvironmental (mu e) concentration estimation; and (3) human activity and breathing rate simulation. In response to an outside peer review of its recent exposure assessments, ASB is deemphasizing modeling the entire population in favor of limited modeling of narrowly defined "sensitive groups." In addition, ASB increasingly is focusing its exposure assessments on those human activities that lead to high intake dose, or high intake dose rate. Examples are provided that highlight these changes in emphasis.

Adult↗