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Improving design, execution and analysis of transcriptomics experimentation

Bruning, O.

Publication date

2015

Document Version

Final published version

Link to publication

Citation for published version (APA):

Bruning, O. (2015). Improving design, execution and analysis of transcriptomics

experimentation.

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Improving Design, Execution &

Analysis of Transcriptomics

Experimentation

Oskar Bruning

Improving Design, Execution & Analysis of T

ranscriptomics Experimentation

O. Bruning

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Improving Design, Execution and Analysis

of Transcriptomics Experimentation

ACADEMISCH PROEFSCHRIFT

ter verkrijging van de graad van doctor

aan de Universiteit van Amsterdam op gezag van de Rector Magnificus

prof. dr. D.C. van den Boom

ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel

op donderdag 19 november 2015, te 10:00 uur

door

Oskar Bruning

geboren te Sliedrecht

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Promotiecommissie:

Promotor(es): Prof. dr. W.J. Stiekema Universiteit van Amsterdam

Copromotor(es): Dr. T.M. Breit Universiteit van Amsterdam

Overige leden: Prof. dr. S. Brul Universiteit van Amsterdam Prof. dr. M.A. Haring Universiteit van Amsterdam Prof. dr. J. Heringa Vrije Universiteit Amsterdam Dr. ir. H.C.J. Hoefsloot Universiteit van Amsterdam Prof. dr. H.P. Spaink Universiteit Leiden

Prof. dr. H. van Steeg Leids Universitair Medisch Centrum

Faculteit der Natuurwetenschappen, Wiskunde en Informatica

The research described in this thesis was carried out at the University of Amsterdam, Swammerdam Institute for Life Sciences, RNA Biology & Applied Bioinformatics.

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“If we knew what it was we were doing, it would not be called research, would it?”

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Table of Contents

Chapter 1: General introduction 7

Chapter 2: The absence of ser389 phosphorylation in p53 affects the basal gene expression level of many p53-dependent genes and alters the biphasic response to uv exposure in

mouse embryonic fibroblasts 17

Chapter 3: Serious complications in gene-expression studies with stress perturbation: An example of UV-exposed p53-mutant

mouse embryonic fibroblasts 45

Chapter 4: RNA isolation for transcriptomics of human and mouse

small skin biopsies 57

Chapter 5: A range finding protocol to support design for transcriptomics experimentation: examples of in-vitro

and in-vivo murine UV exposure 67

Chapter 6: Confounding factors in the transcriptome analysis of an

in-vivo exposure experiment 87

Chapter 7: Concluding Remarks or “Valuable lessons-learne in

transcriptomics experimentation” 117 Summary 126 Samenvatting 130 Published Chapters 134 Acknowledgements/Dankwoord/Danksagung 136 Curriculum vitae 139

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