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Biomedical subjects

Helene H Thygesen

Publications and source records attributed to Helene H Thygesen.

2 recordsLinked to original sources

Modelling the correlation between the activities of adjacent genes in Drosophila.

BACKGROUND: Correlation between the expression levels of genes which are located close to each other on the genome has been found in various organisms, including yeast, drosophila and humans. Since such a correlation could be explained by several biochemical, evolutionary, genetic and technological factors, there is a need for statistical models that correspond to specific biological models for the correlation structure. RESULTS: We modelled the pairwise correlation between the expressions of the genes in a Drosophila microarray experiment as a normal mixture under Fisher's z-transform, and fitted the model to the correlations of expressions of adjacent as well as non-adjacent genes. We also analyzed simulated data for comparison. The model provided a good fit to the data. Further, correlation between the activities of two genes could, in most cases, be attributed to either of two factors: the two genes both being active in the same age group (adult or embryo), or the two genes being in proximity of each other on the chromosome. The interaction between these two factors was weak. CONCLUSIONS: Correlation between the activities of adjacent genes is higher than between non-adjacent genes. In the data we analyzed, this appeared, for the most part, to be a constant effect that applied to all pairs of adjacent genes.

Algorithms↗

Comparing transformation methods for DNA microarray data.

BACKGROUND: When DNA microarray data are used for gene clustering, genotype/phenotype correlation studies, or tissue classification the signal intensities are usually transformed and normalized in several steps in order to improve comparability and signal/noise ratio. These steps may include subtraction of an estimated background signal, subtracting the reference signal, smoothing (to account for nonlinear measurement effects), and more. Different authors use different approaches, and it is generally not clear to users which method they should prefer. RESULTS: We used the ratio between biological variance and measurement variance (which is an F-like statistic) as a quality measure for transformation methods, and we demonstrate a method for maximizing that variance ratio on real data. We explore a number of transformations issues, including Box-Cox transformation, baseline shift, partial subtraction of the log-reference signal and smoothing. It appears that the optimal choice of parameters for the transformation methods depends on the data. Further, the behavior of the variance ratio, under the null hypothesis of zero biological variance, appears to depend on the choice of parameters. CONCLUSIONS: The use of replicates in microarray experiments is important. Adjustment for the null-hypothesis behavior of the variance ratio is critical to the selection of transformation method.

Animals↗