Cover Page
The handle http://hdl.handle.net/1887/19044 holds various files of this Leiden University dissertation.
Author: Anvar, Seyed Yahya
Title: Converging models for transcriptome studies of human diseases : the case of oculopharyngeal muscular dystrophy
Issue Date: 2012-06-06
1 1PB one parent Bayesian network
A A adenine Ala alanine
B BIC Bayes information criterion BNC Bayesian network classifier
C C cytosine
CDF cumulative distribution function CS citrate synthase
CSA cross-sectional area CV cross-validation
D D.E. differentially expressed DAG directed acyclic graph
DAVID database for annotation, visualization, and integrated discovery DNA deoxyribonucleic acid
DUB deubiquitinating enzyme
E E1 ubiquitin-activating enzyme E2 ubiquitin-conjugating enzyme E3 ubiquitin ligase
EDL extensor digitorum longus muscle EF embryonic fibroblast
expPABPN1 expanded Poly(A) Binding Protein Nuclear 1
F FDR false discovery rate
abbreviations
ABBREVIATIONS
190
FVB friend virus B inbred
G G guanine GO gene ontology GT global test
H HF heterochromatic foci
I IND independent
INI intranuclear inclusion
K KEGG Kyoto Encyclopedia of genes and genomes KS Kolmogorov-Smirnov test
L LAS literature-aided association study
M MCMC Markov chain Monte Carlo
MDIC multiple datasets with increasing complexity MIC maximal information coefficient
mRNA messenger ribonucleic acid MyHC myosin heavy chain
N NBC naïve Bayes classifier ND non-deregulated
NPB unlimited Bayesian network NS not significant
NT non-transduced
O OPMD oculopharyngeal muscular dystrophy
P PABPN1 poly(A) binding protein nuclear 1 PCA principal component analysis PPI protein-protein interaction
R RIN RNA integration number RNA-Seq RNA sequencing
RT qPCR reverse transcription polymerase chain reaction
S SNB selective naïve Bayes SOL soleus muscle SSE sum squared error
T T thymine
ABBREVIATIONS
TA tibialis anterior muscle TAN tree augmented network
U Ub ubiquitin
UPS ubiquitin-proteasome system UTR un-translated region
W WT wild-type
Y YFP yellow fluorescent protein
Seyed Yahya Anvar was born on October 11, 1980, in Tehran, Iran. He attended Roozbeh High School, specialised in Mathematics and Physics, in Tehran and graduated in the summer of 1998. He then was admitted to the Industrial Engineering programme at Azad University, Tehran. During the period from 1998 to 2001, he worked as a member of design and develop- ment team at Book City Co., project monitoring and consultancy at Negah Multimedia Co., and system manager and web administrator at Book City online stores. From fall 2002 until July 2006, he did a Bachelors of Information Technology at the Eastern Mediterranean University located in Famagusta (Gazima�usa), Cyprus, and graduated with high-honour. During this time he re-�usa), Cyprus, and graduated with high-honour. During this time he re-usa), Cyprus, and graduated with high-honour. During this time he re- ceived seven high-honour scholarships and one honour scholarship from the Rector.
In September 2006 he began a Masters of Bioinformatics at the Brunel University in London, UK, and received his Masters with distinction in 2007. The work presented as part of his Masters dissertation, entitled Incremental Bayesian Network Models, led to his participation in collabora- tion between dr. Allan Tucker at the Brunel University and dr. Peter-Bram ’t Hoen at the Leiden University Medical Center. He then began to develop new methods to apply Bayesian networks for modelling multiple transcriptome datasets related to myogenesis.
Starting November 2008 he began a PhD at Leiden University, situated at the Center for Human and Clinical Genetics at the Leiden University Medical Center under the supervision of Prof. dr.
Silvère van der Maarel and co-supervision of dr. Peter-Bram ’t Hoen, dr. Vered Raz, and dr. Al-ère van der Maarel and co-supervision of dr. Peter-Bram ’t Hoen, dr. Vered Raz, and dr. Al-re van der Maarel and co-supervision of dr. Peter-Bram ’t Hoen, dr. Vered Raz, and dr. Al- lan Tucker. The PhD focused on the fascinating nature and value of interdisciplinary studies of human disorders. In this thesis, Yahya and colleagues have shown that engaging in the study of diverse biological systems, in the light of evolutionary mechanisms and shared molecular fea- tures (in a rare disease such as oculopharyngeal muscular dystrophy), enabled them to uncover insights on a broad spectrum of conditions and phenomena such as ageing of skeletal muscles and protein aggregation disorders. To do this, he collaborated with centres such as Brunel Univer- sity (dr. Allan Tucker and dr. Veronica Vinciotti), Radboud University Nijmegen Medical Center (Prof. dr. Baziel van Engelen), University of Copenhagen (dr. John Vissing), and Royal Holloway University of London (Prof. dr. George Dickson). During this work, he attended and presented his work at numerous national and international conferences including Netherlands Bioinformatics Conference (NBIC), European Molecular Biology Organization (EMBO), European Society of Hu- man Genetics (ESHG), American Society of Human Genetics and International Congress of Human Genetics (ASHG/ICHG), and International Conference on Intelligent Systems for Molecular Biology (ISMB).
curriculum vitae
CURRICULUM VITAE
194
During his time at LUMC, Yahya has reviewed for number of journals including Bioinformatics, BMC Bioinformatics, PLoS ONE, and BMC Genomics. He was involved in Bioinformatics, Compu- tational Biology of Complex diseases and Ageing (FOS) workshop and MGC course on Technology Facilities. He has also helped organising the Human and Clinical Genetics Party 2009 and Human and Clinical Genetics Day Out 2010.
On May 1, 2011 he received a postdoctoral position at Leiden University Medical Center, Center for Human and Clinical Genetics. He now moves on to the intriguing era of the state-of-the-art genome and transcriptome sequencing. He continues with developing new methodologies to model associations and regulatory relationships. These advancements help to better understand the global organization of networks and biological responses in the study of human genetic dis- orders and other biological conditions. In a slightly different strand, he also has great interests in fine arts, literature, and sports.
Now, it is so that I conclude my thesis by acknowledging the immense efforts and help from a large group of people that made this journey possible. I do not know, cannot guess and have no way of finding out the significance of these contributions. I do know, however, that without them this work would not have been completed. Hereby, I wish to express my grati- tude to those that made this dream a reality.
“The process of scientific discovery is, in fact, a continual flight from wonder.” Albert Einstein
First, none of this would have been possible without Silvère, Peter-Bram, Vered, and Allan. I wish to thank them for giving me the opportunity to work on an interdisciplinary and challenging project. Their fascination with the newest developments in the field of systems biology has made this journey an ultimate learning and rewarding experience which I enjoyed greatly.
“Knowledge is knowing a tomato is a fruit; Wisdom is not putting it in a fruit salad.”
I would have been lost in my project without the guidance of Peter-Bram, Vered, and Allan. Their genuine commitment, hard work and broad area of knowledge inspired me to live each day as if a new fascinating project had just begun. Nevertheless, to paraphrase Darwin, a bioinformatician is a blind man in a dark room looking for a black cat which isn’t there. As curious I might be to try new ideas, it has always been their questions and criticism that enlightened me to find my way around. Thank you for your kindness, friendship, and encouragements.
“I would rather walk with a friend in the dark, than alone in the light.” Helen Keller
I would like to thank my OPMD family, Andrea, Nisha, Eleonora, Hellen, Erik, Daphne, and Merel, not only for being colleagues but as for being good friends, fun times, and their generous support throughout this period. I would like to thank Andrea for playing a key part in our group and for her important contribution on almost every manuscript we wrote. Special thanks to the Frants group for all your help, fun coffee breaks, and interesting conversations. I would like to thank Antoine, Peter T., Dwi, Antonietta, and Laura for friendship, fun times, your enthusiasm, and helpful discussions. A very especial thank to Anita and Babs for their support throughout all the years. Finally, thanks to all others in the Human Genetics department for your help, contribu- tions, and friendship.
“No! Bioinformaticians are not lazy or boring. They are just protective of their seats.”
From the bioinformatics-core, thanks to Judith, Maarten, Herman, Eleni, Irina, Jelle, Erik, Marco, Kostas, and Harish for helpful discussions, friendship, and despite what is perceived by others,
acknowledgement
Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning. Winston Churchill
“ ”
ACKNOWLEDGEMENT
198
thanks for good times. From the LGTC, thanks to Michel, Jeroen, Martijn, Michael, Henk, Ken, Sophie, Yavuz, Arnoud, Rolf for your support and giving me the chance to work in such a great environment. From the Brunel University, thanks Veronica for your collaborative work and con- structive discussions.
“Best friends are those who, when you show up at their door with a dead body, say nothing, grab a shovel, and follow you.”
I’d like to thank my friends for all the memories, good times, laughs, and for your precious friend- ship. Thanks Malin, Elisenda, Jelrik, and Roel for fun times and unforgettable memories. I’ll cher- ish them forever. Thanks Shayan, Saba, Kin, James, Ravi, and Ali E. for your friendship and good times we had back in London. Thanks to Caroline, Rob, Liz, and Reuben for your friendship.
Thank you for empowering me to make my dreams come true and to stand by me.
“The only true wisdom is in knowing you know nothing.” Socrates
First, I would like to thank Ali for our nightlong debates, constructive discussions, and his sup- port. For me, the biggest breakthroughs that helped me decide to go on this path were due to those penetrating conversations. I have to thank Saied, the great, for making this journey a joyful and fun experience. Your sincere friendship helped me through thick and thin.
During all the years of fun, stress, and hard work, I have to thank Fleur for standing by me and making my life truly brilliant. Your patience with me and your unconditional support and com- passion made my life a living dream. Thank you to Oma, Jaap Jan, Inge, and Lisa for welcoming me into your lives and making me feel at home.
Finally, thank you to all of my family. None of this would be possible without the help and sup- port of my siblings. Special thanks to Checkad for playing a big part in enabling me to move for- ward. No word can express my gratitude towards my Mom and Dad. Your passion for knowledge, your encouraging attitude towards one’s betterment, and your ambitious dreams inspired me the most. Your true devotion and lasting belief in me made a dream a reality. For that I love you and I am most grateful. Thank you.
Seyed Yahya Anvar
