Essays on spatial point processes and bioinformatics
This thesis consists of two separate parts. The first part consists of one paper and considers problems concerning spatial point processes and the second part includes three papers in the field of bioinformatics.The first part of the thesis is based on a forestry problem of estimating the number of trees in a region by using the information in an aerial photo, showing the area covered by the trees. The positions of the trees are assumed to follow either a binomial point process or a hard-core Strauss process. Furthermore, discs of equal size are used to represent the tree-crowns. We provide formulas for the expectation and the variance of the relative vacancy for both processes. The formulas are approximate for the hard-core Strauss process. Simulations indicate that the approximations are accurate. The second part of this thesis focuses on pre-processing of microarray data. The microarray technology can be used to measure the expression of thousands of genes simultaneously in a single experiment. The technique is used to identify genes that are differentially expressed between two populations, e.g. diseased versus healthy individuals. This information can be used in several different ways, for example as diagnostic tools and in drug discovery.The microarray technique involves a number of complex experimental steps, where each step introduces variability in the data. Pre-processing aims to reduce this variation and is a crucial part of the data analysis. Paper II gives a review over several pre-processing methods. Spike-in data are used to describe how the different methods affect the sensitivity and bias of the experiment.An important step in pre-processing is dye-normalization. This normalization aims to remove the systematic differences due to the use of different dyes for coloring the samples. In Paper III a novel dye-normalization, the MC-normalization, is proposed. The idea behind this normalization is to let the channels’ individual intensities determine the correction, rather than the average intensity which is the case for the commonly used MA-normalization. Spike-in data showed that the MC-normalization reduced the bias for the differentially expressed genes compared to the MA-normalization.The standard method for preserving patient samples for diagnostic purposes is fixation in formalin followed by embedding in paraffin (FFPE). In Paper IV we used tongue-cancer microRNA-microarray data to study the effect of FFPE-storage. We suggest that the microRNAs are not equally affected by the storage time and propose a novel procedure to remove this bias. The procedure improves the ability of the analysis to detect differentially expressed microRNAs.
Source Type:Doctoral Dissertation
Keywords:SOCIAL SCIENCES; Statistics, computer and systems science; Statistics; Coverage process; vacancy; microarray; pre-processing; sensitivity; bias; dye-normalization; FFPE; storage time effects; Statistics; statistik
Date of Publication:01/01/2010