Universidad Autónoma de Madrid Université de Liège FACULTAD DE MEDICINA

PhD Thesis – Statistical Genetics
STATISTICAL METHODS FOR THE INTEGRATION ANALYSIS OF
–OMICS DATA (GENOMICS, EPIGENOMICS AND TRANSCRIPTOMICS):
AN APPLICATION TO BLADDER CANCER
Author
Silvia Pineda San Juan
Supervisors
Núria Malats
Spanish National Cancer Research Centre
Genetic and Molecular Epidemiology
Madrid, Spain
Kristel Van Steen
Systems and Modeling Unit
Montefiore Institute
Liége, Belgium
Madrid, Spain, September 15th, 2015
Universidad Autónoma de Madrid
FACULTAD DE MEDICINA
Departamento de Medicina Preventiva y
Salud Pública
Université de Liège
SCIENCES APPLIQUÉES
Département d’Electricité, Electronique et
Informatique

Panel Defense
Fernando Rodríguez Artalejo, Ph.D.
(Department of Preventive Medicine and Public Health, UAM, Spain)
Alfonso Valencia, Ph.D.
(Structural Biology and Biocomputing programme, CNIO, Spain)
Douglas Easton, Ph.D.
(Centre for Cancer Genetic Epidemiology, Department of Public Health, Cambridge, UK)
Monika Stoll, Ph.D.
(Department of Genetic Epidemiology, University of Munster, Germany)
Mario F. Fraga, Ph.D.
(Asturias Central University Hospital, CSIC, Spain)
Fátima Al-Shahrour, Ph.D. (Substitute)
(Translational Bioinformatics unit, CNIO, Spain)
Stephan Ossowski, Ph.D. (Substitute)
(Genomic and Epigenomic Variation Disease, CRG, Spain)

To my sister María,
To my parents,
To Mikel,

i
Acknowledgements
In the first place, I would like to thank to my supervisors, Núria Malats and Kristel Van Steen, for
their support during my entire PhD study, for her patience, motivation, enthusiasm, the
immense scientific knowledge and also personal advice that will be all very important in the
development of my career. I thank Núria for giving me the opportunity to work with her and her
group. She trusted me from the beginning and she always encouraged me with new challenges
to make me think and go deeper into each scientific issue. I thank Kristel to agree on this
collaboration and received me in her group for an entire year. I am very happy to have met and
work with both of them and I am very grateful for the opportunity of this joint PhD opportunity.
I also want to give a special thanks to Roger Milne. He guided me two first years I was in the
CNIO when I was completely lost in this new thing it was for me “research”. I learnt many things
from him scientific and personally.
I also want to thank the members of my CNIO committee thesis, Alfonso Valencia, Manuel
Hidalgo and Peter Van Der Spek for their comments and suggestions during my PhD that made
me progress on my research.
I would like to acknowledge the principal investigators, monitors and patients from the Spanish
Bladder Cancer (SBC)/EPICURO study that have generated all the data used in this thesis, and
Francisco Real who has financed the omics data generation and has contributed in many
discussions of this thesis.
I also want to thank Fernando Rodríguez Artalejo, the director of my doctoral program in the
UAM, for all the general talks we have had about science that I really enjoyed. Also to him and
to Axelle Lambotte, from the administrative office in the ULg, for all their help with the
administrative issues from both universities that have been sometimes very complicated and
frustrated.
I also want to thank all the funding support that have made possible this thesis, la Obra Social
Fundación La Caixa, the Short-Term Scientific Mission (STSM) from COST Action BM1204, and
the ULg fellowship for foreign students.
I would like to thank to all the members of the Molecular and Genetic Epidemiology group in
CNIO, to Roger, Toni, Gäelle, Salman, Mat, Raquel, Jesús, André, Alexandra, Marien, Marina that
have already left the group, to Evangelina and Mirari that are here since I started. To Paulina,
Marta, Esther and Veronica that have been the last incorporations to the group. I really want to
thank to all of them for all the discussions we have had in the group, the talks during the lunch,