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Porting Forensic Dna Analysis to Deep Sequencing Porting Forensic Dna Analysis \ PORTING FORENSIC DNA ANALYSIS TO DEEP SEQUENCING PORTING FORENSIC DNA ANALYSIS PORTING FORENSIC DNA ANALYSIS TO DEEP SEQUENCING Christophe Van Neste Christophe Van Christophe Van Neste \ FACULTY OF PHARMACEUTICAL SCIENCES Porting Forensic DNA Analysis To Deep Sequencing Van Neste Christophe Promotor: Prof. D. Deforce Co-promotor: Prof. W. Van Criekinge Co-promotor: Prof. F. Van Nieuwerburgh June 2015 Porting Forensic DNA Analysis To Deep Sequencing Van Neste CHRISTOPHE Dissertation presented in fulfillment of the requirements for the degree of Doctor in Pharmaceutical Sciences Examination committee: Prof. dr. apr. C. Stove, chair Prof. dr. apr. D. Deforce, promotor Prof. dr. ir. W. Van Criekinge, co-promotor Prof. dr. apr. F. Van Nieuwerburgh, co-promotor Prof. dr. B. Bekaert (KU Leuven) Prof. dr. E. De Baere (UGent) Prof. dr. ir. T. De Meyer (UGent) Dr. T. Sijen (NFI, Den Haag) N. Oldroyd (Illumina, London) © 2015 Ghent University – Faculty of Pharmaceutical Sciences Uitgegeven in eigen beheer, Van Neste Christophe, Ottergemsesteenweg 460, B-9000 Ghent (Belgium) Alle rechten voorbehouden. Niets uit deze uitgave mag worden vermenigvuldigd en/of openbaar gemaakt worden door middel van druk, fotokopie, microfilm, elektronisch of op welke andere wijze ook zonder voorafgaande schriftelijke toestemming van de uitgever. All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm, electronic or any other means without written permission from the publisher. ISBN 978-90-5989-804-2 Dedicated to Anastasiya, Sophia and Elena i Preface Here, in front of you is a work of writing. I am not a writer. Although I am officially a philosopher and writing and philosophy seem to go hand in hand in history, as a philosopher I would categorize myself more as a Socratic type. The first people I therefore want to thank is anyone who is reading this. Thank you and bear with me. Although some of the paragraphs could potentially have been written better, some of the paragraphs (including some of the ones just mentioned) do contain some interesting points. Nonetheless, I also thank you for reading it critically. Science and philosophy can only go ahead by scrutinizing all our thoughts. A general thank you to the members of my examination committee for their critical suggestions. My first concrete thanks have to go to my supervisors, Dieter, Wim and Filip. They each played a unique role in the realization of this dissertation. Professor Dieter Deforce, I sincerely thank you for having given me the opportunity to work in your laboratory. You have been the material cause that gave me the possibility to do research in the exciting domain of forensics and without your help there simply would not have been a dissertation. Professor Wim Van Criekinge, a long time ago, in a faculty far far away, you inspired me as a bioinformatician. Little did I know that I would become one myself. Thank you for having been the formal cause in this project. And then there is my efficient cause, professor Filip Van Nieuwerburgh. Sharing the same office, you were the one that kept me going ahead, day to day. I have not counted the number of ii PREFACE iii arguments we had. Sometimes our office sound[ed|s] like the argument clinic, but I sincerely thank you for it. Science cannot go ahead by people thinking exactly the same. And I think we can agree on this, that we both are open-minded enough to change our minds, when the evidence is presented before us. As my material cause was and is the material cause of many, I now embark on the journey of thanking everyone that I met during my years at LabFBT. Mado, as a scientist, although I am your senior in age, you were definitely an inspiration and full of helpful advice in my first two PhD years. Unfortunately, the only thing that remains of your female touch in the office, is your broken yellow thee pot. Nicky, without being cynical, I have to thank you for not having finished your initial analysis of the 454 data. I hope the endeavors you undertook after LabFBT fared you well, and will continue to do so. Bert, you took over Nicky’s cursed seat and could not dispel it. Nonetheless, in the good year you were working here, we had a blast. I am happy that we kept in touch and are still friends. Sander, you are now sitting in the same seat, I am 99.999% sure that the spell has been lifted and foresee a great academic career if you continue your work exactly so. Yannick, so much weight has fallen off my shoulders when you arrived. All the extra time I could put into my doctorate is definitely thanks to you. Dieter, although I was first skeptical of having a fifth member of the office (oxygen-wise), you are a valued addition, and not afraid to participate to the argument clinic when necessary. On my journey, I now leave the IT-crowd behind, and go upstairs, to the strange world of proteomics. Katleen, I definitely have to start with you. I was only just working here, when you already invited me to your PhD defense and shortly after that your wedding. You are such a warm person. Maarten, you are such a crazy person, lovely. Always fun to hear your travel stories, first going around the world, now more down to earth (“Remy boom vallen”;). Marlies, as Mado’s backup you were often in our office to chit-chat on quality and other items. Thank you for the cheerful distractions. Sandra, your persistence in your project and the effort you put in learning some bioinformatics were very inspiring. Trees, thanks for the discussions on forensics, I hope we will have iv PREFACE many more, as it seems a shared passion. Pieter, it was fun having you as a running partner. Thanks for the philosophical talks. For the record: do not forget, I still owe you a kebab. Liesbeth, always there to lighten up the company with your lovely jokes and laughter. Veerle, thanks for all the old tips and new tricks on finishing a PhD. Bart, thanks for finally having chosen python over R. Except for not having a chair, you are the sixth member of our office. It is always a pleasure seeing you enter, and hearing what new scheme you have come up with. Paulien, you always have a fresh perspective to offer. Ellen, you are a whirlwind of energy. Your enthusiasm is infectious. Shahid, I hope you are doing well in Brussels. Elisabeth, you are an excellent kubb captain. It must be the reason why we are finally winning. Lieselot, for a brief moment I thought you were going to be the new Mado in our office, but understandably you fled away from all the IT jokes. Senne, thanks for introducing me again to the wet lab. I will do my best to guide you further in the dry lab. Yens, it will be funny to see you at the other side of the bar. I think a mustache would fit you when you suit up. Sofie, thanks for being a sometimes fellow commuter. It makes getting home after a late team-building activity so much easier. Laura, after this long paragraph I am speechless, but I was determined to include everyone, even the ones that just started, so thank you and good luck. Back on the ground floor, I first have to thank Inge, Astrid and Nadine. Your help with organization and administration has been invaluable to me. Thank you Leen for your sunny personality. A special thanks to David and the forensic analysts: Eveli[en|ne], Petra, Sabine, Saskia and Sylvie. You are the intended end-users of much of the work in this dissertation. I hope we can work closer together in the near future, to make a better program for the forensic community. At the university level, my thanks go to the Multidisciplinary Research Partnership ’Bioinformatics: from nucleotides to networks’ for providing funding for my PhD. It also inspired collaborations: Tim, thanks for the adventures in statistics; Klaas and Michiel, thanks for the experience in scrutinizing documentation. Who knew that my PhD would also take me to the USA? In the first place, I have PREFACE v to thank Cydne. Thank you for your support and always friendly disposition. It gave me the courage to ask about the internship as I figured - worst case scenario - you would have let me known that it was not possible in the nicest of ways. John, thank you for really having made it possible. Mayank, I learned so much from you there, many thanks. The entire BaseSpace team: the kickball breaks were amazing, thanks for including me. Thank you Felix for the talks on statistics. Thanks to anyone I might be forgetting at Illumina. In the final part of this preface, I like to thank the people who are most important to me personally. Thanks mama and papa, specifically for having tolerated me to be a student up to the well-rounded age of 33 (a mature Hobbit now). Thanks Karen and Frederik, for your support and encouragement. Danke nana en bompa, om altijd in mij geloofd te hebben. Grazie Margarita e Salvatore, per tutto l’aiuto materiale e spirituale. Спасибо Георгий и Ольга, даже если вы далеко живете, вы всегда в моем сердце. And finally, thank you Anastasiya. You mean everything to me, I would not have been able to write a single letter without your constant care and love! Ты мой мир, и ты приносишь мне мир. Я тебя люблю! Thank you specifically for the amazing logos and cover design.
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