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Biomedical subjects

Russ Wolfinger

Publications and source records attributed to Russ Wolfinger.

3 recordsLinked to original sources

Generalizable mass spectrometry mining used to identify disease state biomarkers from blood serum.

We bring a "spectrum" of classical data mining and statistical analysis methods to bear on discrimination of two groups of spectra from 24 diseased and 17 normal patients. Our primary goal is to accurately estimate the generalizability of this small dataset. After an aggressive preprocessing step that reduces consideration to only 55 peaks, we conduct over 35 out-of-sample cross-validation simulations of logistic regression, binary decision trees, and linear discriminant analysis. Misclassification rates grow worse as the size of the holdout sample increases, with many exceeding 30 percent. The ability to generalize is clearly tempered by the statistical, instrumentation, and biophysical characteristics of the study.

Biomarkers↗

Mixed models for assessing correlation in the presence of replication.

The need to assess correlation in settings where multiple measurements are available on each of the variables of interest often arises in environmental science. However, this topic is not covered in introductory statistics texts. Although several ad hoc approaches can be used, they can easily lead to invalid conclusions and to a difficult choice of an appropriate measure of the correlation. Lam et al. approached this problem by using maximum likelihood estimation in cases where the replicate measurements are linked over time, but the method requires specialized software. We reanalyze the data of Lam et al. using PROC MIXED in SAS and show how to obtain the parameter estimates of interest with just a few lines of code. We then extend Lam et al.'s method to settings where the replicate measurements are not linked. Analysis of the unlinked case is illustrated with data from a study designed to assess correlations between indoor and outdoor measurements of benzene concentration in the air.

Environmental Monitoring↗

A systematic statistical linear modeling approach to oligonucleotide array experiments.

We outline and describe steps for a statistically rigorous approach to analyzing probe-level Affymetrix GeneChip data. The approach employs classical linear mixed models and operates on a gene-by-gene basis. Forgoing any attempts at gene presence or absence calls, the method simultaneously considers the data across all chips in an experiment. Primary output includes precise estimates of fold change (some as low as 1.1), their statistical significance, and measures of array and probe variability. The method can accommodate complex experiments involving many kinds of treatments and can test for their effects at the probe level. Furthermore, mismatch probe data can be incorporated in different ways or ignored altogether. Data from an ionizing radiation experiment on human cell lines illustrate the key concepts.

Cells, Cultured↗