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\babel@toc {english}{}
\babel@toc {french}{}
\babel@toc {english}{}
\contentsline {chapter}{Acknowledgements}{i}{chapter*.1}
\contentsline {chapter}{Abstract (English/Fran\IeC {\c c}ais/Deutsch)}{iii}{chapter*.2}
\babel@toc {french}{}
\babel@toc {english}{}
\contentsline {chapter}{\numberline {1}Introduction}{1}{chapter.1}
\contentsline {chapter}{Introduction}{1}{chapter.1}
\contentsline {section}{\numberline {1.1}About chromatin}{1}{section.1.1}
\contentsline {subsection}{\numberline {1.1.1}The chromatin structure}{2}{subsection.1.1.1}
\contentsline {subsection}{\numberline {1.1.2}The chromatin is dynamic}{2}{subsection.1.1.2}
\contentsline {subsection}{\numberline {1.1.3}About nucleosome positioning}{4}{subsection.1.1.3}
\contentsline {section}{\numberline {1.2}About transcription factors}{7}{section.1.2}
\contentsline {subsection}{\numberline {1.2.1}TF co-binding}{7}{subsection.1.2.1}
\contentsline {section}{\numberline {1.3}Gene regulation in a nutshell}{9}{section.1.3}
\contentsline {subsection}{\numberline {1.3.1}The chromatin barrier}{9}{subsection.1.3.1}
\contentsline {subsection}{\numberline {1.3.2}TFs cooperative binding}{9}{subsection.1.3.2}
\contentsline {subsection}{\numberline {1.3.3}Pioneer TFs}{10}{subsection.1.3.3}
\contentsline {subsection}{\numberline {1.3.4}Regulatory elements}{10}{subsection.1.3.4}
\contentsline {subsection}{\numberline {1.3.5}The genome goes 3D}{11}{subsection.1.3.5}
\contentsline {section}{\numberline {1.4}Measuring chromatin features}{12}{section.1.4}
\contentsline {subsection}{\numberline {1.4.1}Measuring TF binding in vivo}{12}{subsection.1.4.1}
\contentsline {subsection}{\numberline {1.4.2}Measuring TF binding in vitro}{13}{subsection.1.4.2}
\contentsline {subsection}{\numberline {1.4.3}Measuring nucleosome occupancy}{14}{subsection.1.4.3}
\contentsline {subsection}{\numberline {1.4.4}Digital footprinting}{15}{subsection.1.4.4}
\contentsline {section}{\numberline {1.5}Modeling sequence specificity}{17}{section.1.5}
\contentsline {subsubsection}{The physics approach to PWMs}{17}{section.1.5}
\contentsline {subsubsection}{The statistical mechanic approach to PWMs}{18}{equation.1.5.2}
\contentsline {subsection}{\numberline {1.5.1}Aligning binding sites}{19}{subsection.1.5.1}
\contentsline {subsection}{\numberline {1.5.2}Platitudes}{20}{subsection.1.5.2}
\contentsline {subsection}{\numberline {1.5.3}Predicting binding sites}{20}{subsection.1.5.3}
\contentsline {section}{\numberline {1.6}Over-represented patterns discovery}{21}{section.1.6}
\contentsline {section}{\numberline {1.7}General aims of this work}{23}{section.1.7}
\contentsline {chapter}{\numberline {2}Laboratory resources}{25}{chapter.2}
\contentsline {chapter}{Laboratory resources}{25}{chapter.2}
\contentsline {section}{\numberline {2.1}Mass Genome Annotation repository}{25}{section.2.1}
\contentsline {subsection}{\numberline {2.1.1}MGA content and organization}{26}{subsection.2.1.1}
\contentsline {subsection}{\numberline {2.1.2}Conclusions}{27}{subsection.2.1.2}
\contentsline {section}{\numberline {2.2}Eukaryotic Promoter Database}{28}{section.2.2}
\contentsline {subsection}{\numberline {2.2.1}EPDnew now annotates (some of) your mushrooms and vegetables}{29}{subsection.2.2.1}
\contentsline {subsection}{\numberline {2.2.2}Increased mapping precision in human}{30}{subsection.2.2.2}
\contentsline {subsection}{\numberline {2.2.3}Integration of EPDnew with other resources}{31}{subsection.2.2.3}
\contentsline {subsection}{\numberline {2.2.4}Conclusions}{31}{subsection.2.2.4}
\contentsline {subsection}{\numberline {2.2.5}Methods}{31}{subsection.2.2.5}
\contentsline {subsubsection}{Motif occurrence profiles}{31}{subsection.2.2.5}
\contentsline {chapter}{\numberline {3}ENCODE peaks analysis}{33}{chapter.3}
\contentsline {chapter}{ENCODE peaks analysis}{33}{chapter.3}
\contentsline {section}{\numberline {3.1}Data}{34}{section.3.1}
\contentsline {section}{\numberline {3.2}ChIPPartitioning : an algorithm to identify chromatin architectures}{35}{section.3.2}
\contentsline {subsection}{\numberline {3.2.1}Data realignment}{37}{subsection.3.2.1}
\contentsline {section}{\numberline {3.3}Nucleosome organization around transcription factor binding sites}{37}{section.3.3}
\contentsline {section}{\numberline {3.4}The case of CTCF, RAD21, SMC3, YY1 and ZNF143}{40}{section.3.4}
\contentsline {section}{\numberline {3.5}CTCF and JunD interactomes}{46}{section.3.5}
\contentsline {section}{\numberline {3.6}EBF1 binds nucleosomes}{48}{section.3.6}
\contentsline {section}{\numberline {3.7}Discussion}{50}{section.3.7}
\contentsline {section}{\numberline {3.8}Methods}{51}{section.3.8}
\contentsline {subsection}{\numberline {3.8.1}Data and data processing}{51}{subsection.3.8.1}
\contentsline {subsection}{\numberline {3.8.2}Classification of MNase patterns}{52}{subsection.3.8.2}
\contentsline {subsection}{\numberline {3.8.3}Quantifying nucleosome array intensity from classification results}{53}{subsection.3.8.3}
\contentsline {subsection}{\numberline {3.8.4}Peak colocalization}{54}{subsection.3.8.4}
\contentsline {subsection}{\numberline {3.8.5}NDR detection}{54}{subsection.3.8.5}
\contentsline {subsection}{\numberline {3.8.6}CTCF and JunD interactors}{57}{subsection.3.8.6}
\contentsline {subsection}{\numberline {3.8.7}EBF1 and nucleosome}{58}{subsection.3.8.7}
\contentsline {chapter}{\numberline {4}SPar-K}{61}{chapter.4}
\contentsline {section}{\numberline {4.1}Algorithm}{62}{section.4.1}
\contentsline {section}{\numberline {4.2}Implementation}{63}{section.4.2}
\contentsline {section}{\numberline {4.3}Benchmarking}{63}{section.4.3}
\contentsline {subsection}{\numberline {4.3.1}K-means}{66}{subsection.4.3.1}
\contentsline {subsection}{\numberline {4.3.2}ChIPPartitioning}{66}{subsection.4.3.2}
\contentsline {subsection}{\numberline {4.3.3}Data}{66}{subsection.4.3.3}
\contentsline {subsection}{\numberline {4.3.4}Performances}{67}{subsection.4.3.4}
\contentsline {section}{\numberline {4.4}Partition of DNase and MNase data}{67}{section.4.4}
\contentsline {section}{\numberline {4.5}Conclusions}{70}{section.4.5}
\contentsline {chapter}{\numberline {5}SMiLE-seq data analysis}{71}{chapter.5}
\contentsline {chapter}{SMiLE-seq data analysis}{71}{chapter.5}
\contentsline {section}{\numberline {5.1}Introduction}{71}{section.5.1}
\contentsline {section}{\numberline {5.2}Hidden Markov Model Motif discovery}{73}{section.5.2}
\contentsline {section}{\numberline {5.3}Binding motif evaluation}{74}{section.5.3}
\contentsline {section}{\numberline {5.4}Results}{75}{section.5.4}
\contentsline {section}{\numberline {5.5}Conclusions}{77}{section.5.5}
\contentsline {chapter}{\numberline {6}PWMScan}{79}{chapter.6}
\contentsline {section}{\numberline {6.1}Algorithms}{79}{section.6.1}
\contentsline {subsection}{\numberline {6.1.1}Scanner algorithm}{80}{subsection.6.1.1}
\contentsline {subsection}{\numberline {6.1.2}Matches enumeration and mapping}{80}{subsection.6.1.2}
\contentsline {section}{\numberline {6.2}PMWScan architecture}{81}{section.6.2}
\contentsline {section}{\numberline {6.3}Benchmark}{83}{section.6.3}
\contentsline {section}{\numberline {6.4}Conclusions}{85}{section.6.4}
\contentsline {chapter}{\numberline {7}Chromatin accessibility of monocytes}{87}{chapter.7}
\contentsline {section}{\numberline {7.1}Monitoring TF binding}{87}{section.7.1}
\contentsline {section}{\numberline {7.2}The advent of single cell DGF}{88}{section.7.2}
\contentsline {section}{\numberline {7.3}Open issues}{88}{section.7.3}
\contentsline {section}{\numberline {7.4}Data}{88}{section.7.4}
\contentsline {section}{\numberline {7.5}Identifying over-represented signals}{89}{section.7.5}
\contentsline {subsection}{\numberline {7.5.1}ChIPPartitioning algorithm}{89}{subsection.7.5.1}
\contentsline {subsection}{\numberline {7.5.2}EMSequence algorithm}{89}{subsection.7.5.2}
\contentsline {subsubsection}{without shift and flip}{91}{figure.caption.35}
\contentsline {subsubsection}{with shift and flip}{91}{equation.7.5.2}
\contentsline {subsection}{\numberline {7.5.3}EMJoint algorithm}{93}{subsection.7.5.3}
\contentsline {subsection}{\numberline {7.5.4}Data realignment}{94}{subsection.7.5.4}
\contentsline {subsection}{\numberline {7.5.5}Soft aggregation plots}{94}{subsection.7.5.5}
\contentsline {section}{\numberline {7.6}Data processing}{95}{section.7.6}
\contentsline {section}{\numberline {7.7}Results}{95}{section.7.7}
\contentsline {subsection}{\numberline {7.7.1}Aligning the binding sites}{95}{subsection.7.7.1}
\contentsline {subsection}{\numberline {7.7.2}Exploring individual TF classes}{97}{subsection.7.7.2}
\contentsline {section}{\numberline {7.8}Discussions}{99}{section.7.8}
\contentsline {section}{\numberline {7.9}Methods}{100}{section.7.9}
\contentsline {subsection}{\numberline {7.9.1}Code availability}{100}{subsection.7.9.1}
\contentsline {subsection}{\numberline {7.9.2}Data sources}{100}{subsection.7.9.2}
\contentsline {subsection}{\numberline {7.9.3}Data post-processing}{101}{subsection.7.9.3}
\contentsline {subsection}{\numberline {7.9.4}Model extension}{101}{subsection.7.9.4}
\contentsline {subsection}{\numberline {7.9.5}Extracting data assigned to a class}{102}{subsection.7.9.5}
\contentsline {subsection}{\numberline {7.9.6}Programs}{104}{subsection.7.9.6}
\contentsline {subsection}{\numberline {7.9.7}Fragment classes}{105}{subsection.7.9.7}
\contentsline {subsection}{\numberline {7.9.8}Simulated sequences}{106}{subsection.7.9.8}
\contentsline {subsection}{\numberline {7.9.9}Binding site prediction}{106}{subsection.7.9.9}
\contentsline {subsection}{\numberline {7.9.10}Realignment using JASPAR motifs}{107}{subsection.7.9.10}
\contentsline {subsection}{\numberline {7.9.11}Per TF sub-classes}{109}{subsection.7.9.11}
\contentsline {chapter}{\numberline {8}Discussion}{111}{chapter.8}
\contentsline {chapter}{Discussion}{111}{chapter.8}
\contentsline {chapter}{\numberline {9}Published articles}{115}{chapter.9}
\vspace {\normalbaselineskip }
\contentsline {chapter}{\numberline {A}Supplementary material}{117}{appendix.A}
\contentsline {section}{\numberline {A.1}ENCODE peaks analysis supplementary material}{118}{section.A.1}
\contentsline {section}{\numberline {A.2}SPar-K supplementary material}{128}{section.A.2}
\contentsline {section}{\numberline {A.3}SMiLE-seq supplementary material}{141}{section.A.3}
\contentsline {section}{\numberline {A.4}Chromatin accessibility of monocytes supplementary material}{141}{section.A.4}
\contentsline {subsection}{\numberline {A.4.1}Fragment size analysis}{141}{subsection.A.4.1}
\contentsline {subsection}{\numberline {A.4.2}Measuring open chromatin and nucleosome occupancy}{142}{subsection.A.4.2}
\contentsline {subsection}{\numberline {A.4.3}Evaluation of EMSequence and ChIPPartitioning}{145}{subsection.A.4.3}
\contentsline {subsubsection}{EMSequence}{145}{subsection.A.4.3}
\contentsline {subsubsection}{ChIPPartitioning}{148}{figure.caption.56}
\contentsline {subsection}{\numberline {A.4.4}Other supplementary figures}{151}{subsection.A.4.4}
\contentsline {chapter}{Bibliography}{155}{section*.64}
\contentsline {chapter}{Bibliography}{168}{appendix*.65}
\contentsline {chapter}{Curriculum Vitae}{169}{section*.66}
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