Search PubMed⌕ Search

Biomedical subjects

K Boucher

Publications and source records attributed to K Boucher.

10 recordsLinked to original sources
PubMed2002

Variable selection and pattern recognition with gene expression data generated by the microarray technology.

Lack of adequate statistical methods for the analysis of microarray data remains the most critical deterrent to uncovering the true potential of these promising techniques in basic and translational biological studies. The popular practice of drawing important biological conclusions from just one replicate (slide) should be discouraged. In this paper, we discuss some modern trends in statistical analysis of microarray data with a special focus on statistical classification (pattern recognition) and variable selection. In addressing these issues we consider the utility of some distances between random vectors and their nonparametric estimates obtained from gene expression data. Performance of the proposed distances is tested by computer simulations and analysis of gene expression data on two different types of human leukemia. In experimental settings, the error rate is estimated by cross-validation, while a control sample is generated in computer simulation experiments aimed at testing the proposed gene selection procedures and associated classification rules.

Computer Simulation↗
PubMed2001

An alternative stochastic model of generation of oligodendrocytes in cell culture.

According to our previous model, oligodendrocyte--type 2 (O-2A) astrocyte progenitor cells become competent for differentiation in vitro after they complete a certain number of critical mitotic cycles. After attaining the competency to differentiate, progenitor cells divide with fixed probability p in subsequent cycles. The number of critical cycles is random; analysis of data suggests that it varies from zero to two. The present paper presents an alternative model in which there are no critical cycles, and the probability that a progenitor cell will divide again decreases gradually to a plateau value as the number of completed mitotic cycles increases. In particular all progenitor cells have the ability to differentiate from the time of plating. The Kiefer-Wolfowitz procedure is used to fit the new model to experimental data on the clonal growth of purified O-2A progenitor cells obtained from the optic nerves of 7 day old rats. The new model is shown to fit the experimental data well, indicating that it is not possible to determine whether critical cycles exist on the basis of these experimental data. In contrast to the fit of the previous model, which suggested that the addition of thyroid hormone increased the limiting probability of differentiation as the number of mitotic cycles increases, the fit of the new model suggests that the addition of thyroid hormone has almost no effect on the limiting probability of differentiation.

Animals↗
PubMed1999

The shape of the hazard function in breast carcinoma: curability of the disease revisited.

BACKGROUND: The question of curability of breast carcinoma remains controversial. Because the probability of cure essentially is an asymptotic notion, the corresponding estimation problems call for special statistical methods. Such methods should account for an intimate connection between the probability of cure and the shape of the hazard function. METHODS: The study was performed on survival data for 13,166 women with breast carcinoma identified through the Utah Cancer Registry and stratified by clinical stage and age at diagnosis. For these patients, the follow-up period was 30 years. Three estimation procedures were used for estimating the hazard function from the data: the life table estimator, a kernel counterpart of the Nelson-Aalen estimator, and a parametric estimator specifically designed for two-component hazards. The parametric estimate of the hazard function was used to provide estimates of cure rates for each category of patients. RESULTS: For all categories of patients under study, the estimated hazard functions passed through a clear-cut maximum, showing a tendency to decrease as time approached the end of a follow-up period. The hazards appeared to be nonproportional across the strata. The estimated values of the cure rate and the corresponding confidence intervals were determined for each stratum of patients with breast carcinoma. CONCLUSIONS: The results of the current study strongly suggest that cure is a possible outcome of breast carcinoma treatment. The condition of proportionality of risks is not met in breast carcinoma survival data.

Adult↗
PubMed1999

Modeling insight into spontaneous regression of tumors.

The phenomenon of spontaneous regression of benign and malignant tumors is well documented in the literature and is commonly attributed to the induction of apoptosis or activation of the immune system. We attempt at evaluating the role of random effects in this phenomenon. To this end, we consider a stochastic model of tumor growth which is descriptive of the fact that tumors are inherently prone to spontaneous regression due to the random nature of their development. The model describes a population of actively proliferating cells which may give rise to differentiated cells. The process of cell differentiation is irreversible and terminates in cell death. We formulate the model in terms of temporally inhomogeneous Markov branching processes with two types of cells so that the expected total number of neoplastic cells is consistent with the observed mean growth kinetics. Within the framework of this model, the extinction probability for proliferating cells tends to one as time tends to infinity. Given the event of nonextinction, the distribution of tumor size is asymptotically exponential. The limiting conditional distribution of tumor size is in good agreement with epidemiologic data on advanced lung cancer.

Humans↗
PubMed1999

A stochastic model of temporally regulated generation of oligodendrocytes in cell culture.

The results of our previous analyses suggest that O-2A progenitor cells become competent for differentiation in vitro after they complete a certain number of critical mitotic cycles. The number of critical cycles varies from clone to clone and should be thought of as a random variable. We propose an approach to the analysis of oligodendrocyte generation in vitro based on a stochastic model allowing for an arbitrary distribution of this random variable with a finite support. When applied to experimental data on clonal growth and differentiation of purified O-2A progenitor cells obtained from optic nerves of 1 and 7 day-old rats, the model provides a good quantitative description not only of the first two moments (mean and variance) of the number of O-2A progenitor cells and oligodendrocytes at different times after the start of experiment, but of the corresponding distributions as well. As our estimates show, there are scarcely any O-2A progenitor cells that divide in vitro more than twice before they acquire the competence for differentiation. Those O-2A cells that have undergone the critical divisions differentiate into an oligodendrocyte in each of the subsequent mitotic cycles with a certain probability. We give estimates of this probability for O-2A cells under different growth conditions. Our analysis suggests that the effect of thyroid hormone is twofold: it reduces the mean duration of the mitotic cycle for progenitor cells, and it increases the probability of their transformation into oligodendrocytes.

Animals↗
PubMed1998

Quantitative insight into proliferation and differentiation of oligodendrocyte type 2 astrocyte progenitor cells in vitro.

As part of our attempts at understanding fundamental principles that underlie the generation of nondividing terminally differentiated progeny from dividing precursor cells, we have developed approaches to a quantitative analysis of proliferation and differentiation of oligodendrocyte type 2 astrocyte (O-2A) progenitor cells at the clonal level. Owing to extensive previous studies of clonal differentiation in this lineage, O-2A progenitor cells represent an excellent system for such an analysis. Previous studies have resulted in two competing hypotheses; one of them suggests that progenitor cell differentiation is symmetric, the other hypothesis introduces an asymmetric process of differentiation. We propose a general model that incorporates both such extreme hypotheses as special cases. Our analysis of experimental data has shown, however, that neither of these extreme cases completely explains the observed kinetics of O-2A progenitor cell proliferation and oligodendrocyte generation in vitro. Instead, our results indicate that O-2A progenitor cells become competent for differentiation after they complete a certain number of critical mitotic cycles that represent a period of symmetric development. This number varies from clone to clone and may be thought of as a random variable; its probability distribution was estimated from experimental data. Those O-2A cells that have undergone the critical divisions then may differentiate into an oligodendrocyte in each of the subsequent mitotic cycles with a certain probability, thereby exhibiting the asymmetric type of differentiation.

Animals↗
PubMed1998

A model of multiple tumorigenesis allowing for cell death: quantitative insight into biological effects of urethane.

This paper considers the utility of a stochastic model of carcinogenesis proposed by Yakovlev and Polig [Math. Biosci. 132 (1996) 1-33] in the analysis of experimental data on multiple tumors induced by chemical carcinogens. The model provides a good description of published data on multiple tumors developing in the lungs of mice in response to different schedules of urethane. The distribution of pulmonary tumor counts appears to be negative binomial for each period of time after exposure to urethane. Our results suggest that the rate of administration of urethane has little effect both on the mean number of initiated cells per unit dose and on the rate of formation of lesions responsible for cell death. As our estimates show, more than 80% of initiated cells die in the course of tumor promotion. The model is robust to variations in the rate of urethane excretion given a fixed total dose of the carcinogen. Some prospects for further development of the model to allow for expansion of promoted cell clones are discussed.

Animals↗
PubMedDate not supplied

A person, not a disease.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗