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Biomedical subjects

Andrei Y Yakovlev

Publications and source records attributed to Andrei Y Yakovlev.

4 recordsLinked to original sources

Utility of correlation measures in analysis of gene expression.

The role of the correlation structure of gene expression data are two-fold: It is a source of complications and useful information at the same time. Ignoring the strong stochastic dependence between gene expression levels in statistical methodologies for microarray data analysis may deteriorate their performance. However, there is a host of valuable information in the correlation structure that deserves a closer look. A proper use of correlation measures can remedy deficiencies of currently practiced methods that are focused too heavily on strong effects in terms of differential expression of genes. The present paper discusses the utility of correlation measures in microarray data analysis and gene regulatory network reconstruction, along with various pitfalls in both research areas that have been uncovered in methodological studies. These issues have broad applicability to all genomic studies examining the biology, diagnosis, and treatment of neurological disorders.

Animals↗

The University of Rochester model of breast cancer detection and survival.

This paper presents a biologically motivated model of breast cancer development and detection allowing for arbitrary screening schedules and the effects of clinical covariates recorded at the time of diagnosis on posttreatment survival. Biologically meaningful parameters of the model are estimated by the method of maximum likelihood from the data on age and tumor size at detection that resulted from two randomized trials known as the Canadian National Breast Screening Studies. When properly calibrated, the model provides a good description of the U.S. national trends in breast cancer incidence and mortality. The model was validated by predicting some quantitative characteristics obtained from the Surveillance, Epidemiology, and End Results data. In particular, the model provides an excellent prediction of the size-specific age-adjusted incidence of invasive breast cancer as a function of calendar time for 1975-1999. Predictive properties of the model are also illustrated with an application to the dynamics of age-specific incidence and stage-specific age-adjusted incidence over 1975-1999.

Age Factors↗

Effect of screening and adjuvant therapy on mortality from breast cancer.

BACKGROUND: We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS: A consortium of investigators developed seven independent statistical models of breast-cancer incidence and mortality. All seven groups used the same sources to obtain data on the use of screening mammography, adjuvant treatment, and benefits of treatment with respect to the rate of death from breast cancer. RESULTS: The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28 to 65 percent (median, 46 percent), with adjuvant treatment contributing the rest. The variability across models in the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty associated with estimating the benefit of screening. CONCLUSIONS: Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States.

Adult↗

Multivariate exploratory tools for microarray data analysis.

The ultimate success of microarray technology in basic and applied biological sciences depends critically on the development of statistical methods for gene expression data analysis. The most widely used tests for differential expression of genes are essentially univariate. Such tests disregard the multidimensional structure of microarray data. Multivariate methods are needed to utilize the information hidden in gene interactions and hence to provide more powerful and biologically meaningful methods for finding subsets of differentially expressed genes. The objective of this paper is to develop methods of multidimensional search for biologically significant genes, considering expression signals as mutually dependent random variables. To attain these ends, we consider the utility of a pertinent distance between random vectors and its empirical counterpart constructed from gene expression data. The distance furnishes exploratory procedures aimed at finding a target subset of differentially expressed genes. To determine the size of the target subset, we resort to successive elimination of smaller subsets resulting from each step of a random search algorithm based on maximization of the proposed distance. Different stopping rules associated with this procedure are evaluated. The usefulness of the proposed approach is illustrated with an application to the analysis of two sets of gene expression data.

Algorithms↗