Each cancer is unique: it reflects the underlying genetic make-up of the patient and the stochastic mutational processes that occur within the tumour. This uniqueness suggests that each patient should receive a personalized type of therapy. Current predictions of a cancer patient’s outcome or prognosis are highly inaccurate. To aid in the prediction of patient prognosis based on highthroughput molecular datasets I have worked to optimize each step of the experimental pipeline: platform annotation, experimental design, consideration of tumour heterogeneity, data pre-processing and statistical analysis, and feature selection. First, a 12k CpG Island clone library was sequenced and annotated using a BLAT analysis. Second, microarrays built using this library were used in a fully-saturated study to evaluate the importance of ChIP-chip experimental design parameters. Third, intra-tumour heterogeneity was shown to influence specific pathways in a large fraction of genes. Fourth, a systematic empirical evaluation of 19,446 combinations of microarray analysis methods identified key steps of the analysis process and provided insight into their optimization. Finally, the combination of a two-stage experimental design and a novel semi-supervised algorithm yielded a six-gene, mRNA abundance-based classifier that could divide non-small cell lung cancer patients into two groups with significantly different outcomes in four independent validation cohorts. Further, a permutation study showed that millions of six-gene markers exist, but that ours ranked amongst the top 99.98% of all six-gene markers. The knowledge gained from these studies provides a key foundation for the development of personalized therapies for cancer patients.

Proefschr. Rijksuniversiteit Groningen. / Met bibliogr., lit.opg.-Met samenvatting in het Nederlands.

Thesis Erasmus University Rotterdam. / With bibliogr., with a summary in Dutch.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Northeastern University, 2008. / Title from title page (viewed March 9, 2009). Graduate School of Arts and Sciences, Dept. of Chemistry and Chemical Biology. Includes bibliographical references (p. 255-279).

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 127-146) Also available in print.

Diss. (sammanfattning) Göteborg : Univ., 2008. / Härtill 3 uppsatser.

Thesis (Ph. D.)--Colorado State University, 2004. / Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 148-187).