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\babel@toc {english}{}
\babel@toc {french}{}
\babel@toc {english}{}
\contentsline {chapter}{Acknowledgements}{i}{chapter*.1}
\contentsline {chapter}{Preface}{iii}{chapter*.2}
\contentsline {chapter}{Abstract (English/Fran\IeC {\c c}ais/Deutsch)}{v}{chapter*.3}
\babel@toc {german}{}
\babel@toc {english}{}
\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 component features}{12}{section.1.4}
\contentsline {subsection}{\numberline {1.4.1}Measuring nucleosome occupancy}{12}{subsection.1.4.1}
\contentsline {subsection}{\numberline {1.4.2}Measuring TF binding in vivo}{13}{subsection.1.4.2}
\contentsline {subsection}{\numberline {1.4.3}Measuring TF binding in vitro}{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.1.5.1}
\contentsline {subsection}{\numberline {1.5.1}Aligning binding sites}{19}{subsection.1.5.1}
\contentsline {subsection}{\numberline {1.5.2}Platitudes}{19}{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}{20}{section.1.6}
\contentsline {chapter}{\numberline {2}Laboratory resources}{23}{chapter.2}
\contentsline {chapter}{Laboratory resources}{23}{chapter.2}
\contentsline {section}{\numberline {2.1}Mass Genome Annotation repository}{23}{section.2.1}
\contentsline {subsection}{\numberline {2.1.1}MGA content and organization}{24}{subsection.2.1.1}
\contentsline {subsection}{\numberline {2.1.2}Conclusions}{26}{subsection.2.1.2}
\contentsline {section}{\numberline {2.2}Eukaryotic Promoter Database}{27}{section.2.2}
\contentsline {subsection}{\numberline {2.2.1}EPDnew now annotates (some of) your mushrooms and vegetables}{28}{subsection.2.2.1}
\contentsline {subsection}{\numberline {2.2.2}Increased mapping precision in human}{29}{subsection.2.2.2}
\contentsline {subsection}{\numberline {2.2.3}Integration of EPDnew with other resources}{29}{subsection.2.2.3}
\contentsline {subsection}{\numberline {2.2.4}Conclusions}{30}{subsection.2.2.4}
\contentsline {subsection}{\numberline {2.2.5}Methods}{30}{subsection.2.2.5}
\contentsline {subsubsection}{Motif occurrence profiles}{30}{subsection.2.2.5}
\contentsline {chapter}{\numberline {3}ENCODE peaks analysis}{31}{chapter.3}
\contentsline {chapter}{ENCODE peaks analysis}{31}{chapter.3}
\contentsline {section}{\numberline {3.1}Data}{31}{section.3.1}
\contentsline {section}{\numberline {3.2}ChIPPartitioning : an algorithm to identify chromatin architectures}{33}{section.3.2}
\contentsline {subsection}{\numberline {3.2.1}Data realignment}{34}{subsection.3.2.1}
\contentsline {section}{\numberline {3.3}Nucleosome organization around transcription factor binding sites}{35}{section.3.3}
\contentsline {section}{\numberline {3.4}The case of CTCF, RAD21, SMC3, YY1 and ZNF143}{37}{section.3.4}
\contentsline {section}{\numberline {3.5}CTCF and JunD interactomes}{41}{section.3.5}
\contentsline {section}{\numberline {3.6}EBF1 binds nucleosomes}{45}{section.3.6}
\contentsline {section}{\numberline {3.7}Discussion}{48}{section.3.7}
\contentsline {section}{\numberline {3.8}Methods}{48}{section.3.8}
\contentsline {subsection}{\numberline {3.8.1}Data and data processing}{48}{subsection.3.8.1}
\contentsline {subsection}{\numberline {3.8.2}Classification of MNase patterns}{49}{subsection.3.8.2}
\contentsline {subsection}{\numberline {3.8.3}Quantifying nucleosome array intensity from classification results}{50}{subsection.3.8.3}
\contentsline {subsection}{\numberline {3.8.4}Peak colocalization}{51}{subsection.3.8.4}
\contentsline {subsection}{\numberline {3.8.5}NDR detection}{52}{subsection.3.8.5}
\contentsline {subsection}{\numberline {3.8.6}CTCF and JunD interactors}{54}{subsection.3.8.6}
\contentsline {subsection}{\numberline {3.8.7}EBF1 and nucleosome}{55}{subsection.3.8.7}
\contentsline {chapter}{\numberline {4}SPar-K}{57}{chapter.4}
\contentsline {section}{\numberline {4.1}Algorithm}{57}{section.4.1}
\contentsline {section}{\numberline {4.2}Implementation}{58}{section.4.2}
\contentsline {section}{\numberline {4.3}Benchmarking}{59}{section.4.3}
\contentsline {subsection}{\numberline {4.3.1}K-means}{59}{subsection.4.3.1}
\contentsline {subsection}{\numberline {4.3.2}ChIPPartitioning}{62}{subsection.4.3.2}
\contentsline {subsection}{\numberline {4.3.3}Data}{62}{subsection.4.3.3}
\contentsline {subsection}{\numberline {4.3.4}Performances}{63}{subsection.4.3.4}
\contentsline {section}{\numberline {4.4}Partition of DNase and MNase data}{63}{section.4.4}
\contentsline {section}{\numberline {4.5}Conclusions}{63}{section.4.5}
\contentsline {chapter}{\numberline {5}SMiLE-seq data analysis}{67}{chapter.5}
\contentsline {chapter}{SMiLE-seq data analysis}{67}{chapter.5}
\contentsline {section}{\numberline {5.1}Introduction}{67}{section.5.1}
\contentsline {section}{\numberline {5.2}Hidden Markov Model Motif discovery}{69}{section.5.2}
\contentsline {section}{\numberline {5.3}Binding motif evaluation}{70}{section.5.3}
\contentsline {section}{\numberline {5.4}Results}{71}{section.5.4}
\contentsline {section}{\numberline {5.5}Conclusions}{73}{section.5.5}
\contentsline {chapter}{\numberline {6}PWMScan}{75}{chapter.6}
\contentsline {section}{\numberline {6.1}Algorithms}{75}{section.6.1}
\contentsline {subsection}{\numberline {6.1.1}Scanner algorithm}{76}{subsection.6.1.1}
\contentsline {subsection}{\numberline {6.1.2}Matches enumeration and mapping}{76}{subsection.6.1.2}
\contentsline {section}{\numberline {6.2}PMWScan architecture}{77}{section.6.2}
\contentsline {section}{\numberline {6.3}Benchmark}{79}{section.6.3}
\contentsline {section}{\numberline {6.4}Conclusions}{81}{section.6.4}
\contentsline {chapter}{\numberline {7}Chromatin accessibility of monocytes}{83}{chapter.7}
\contentsline {section}{\numberline {7.1}Monitoring TF binding}{83}{section.7.1}
\contentsline {section}{\numberline {7.2}The advent of single cell DGF}{84}{section.7.2}
\contentsline {section}{\numberline {7.3}Open issues}{84}{section.7.3}
\contentsline {section}{\numberline {7.4}Data}{84}{section.7.4}
\contentsline {section}{\numberline {7.5}Identifying over-represented signals}{85}{section.7.5}
\contentsline {subsection}{\numberline {7.5.1}ChIPPartitioning : an algorithm to identify over-represented read patterns}{85}{subsection.7.5.1}
\contentsline {subsection}{\numberline {7.5.2}EMSequence : an algorithm to identify over-represented sequences}{85}{subsection.7.5.2}
\contentsline {subsubsection}{without shift and flip}{87}{figure.caption.36}
\contentsline {subsubsection}{with shift and flip}{87}{equation.7.5.2}
\contentsline {subsection}{\numberline {7.5.3}EMJoint : an algorithm to identify over-represented sequences and chromatin architectures}{88}{subsection.7.5.3}
\contentsline {subsection}{\numberline {7.5.4}Data realignment}{89}{subsection.7.5.4}
\contentsline {section}{\numberline {7.6}Results}{90}{section.7.6}
\contentsline {subsection}{\numberline {7.6.1}Fragment size analysis}{92}{subsection.7.6.1}
\contentsline {subsection}{\numberline {7.6.2}Measuring open chromatin and nucleosome occupancy}{92}{subsection.7.6.2}
\contentsline {subsection}{\numberline {7.6.3}Evaluation of EMSequence and ChIPPartitioning}{94}{subsection.7.6.3}
\contentsline {subsubsection}{EMSequence}{95}{subsection.7.6.3}
\contentsline {subsubsection}{ChIPPartitioning}{97}{figure.caption.41}
\contentsline {section}{\numberline {7.7}Aligning the binding sites}{99}{section.7.7}
\contentsline {section}{\numberline {7.8}Exploring individual TF classes}{103}{section.7.8}
\contentsline {section}{\numberline {7.9}Discussions}{103}{section.7.9}
\contentsline {section}{\numberline {7.10}Perspectives}{104}{section.7.10}
\contentsline {section}{\numberline {7.11}Methods}{105}{section.7.11}
\contentsline {subsection}{\numberline {7.11.1}Partitioning programs}{105}{subsection.7.11.1}
\contentsline {subsection}{\numberline {7.11.2}Fragment classes}{105}{subsection.7.11.2}
\contentsline {subsection}{\numberline {7.11.3}Simulated sequences}{106}{subsection.7.11.3}
\contentsline {subsection}{\numberline {7.11.4}Realignment using JASPAR motifs}{106}{subsection.7.11.4}
\contentsline {subsection}{\numberline {7.11.5}Model extension}{108}{subsection.7.11.5}
\contentsline {subsection}{\numberline {7.11.6}Extracting data assigned to a class}{108}{subsection.7.11.6}
\contentsline {subsection}{\numberline {7.11.7}Peak processing}{111}{subsection.7.11.7}
\contentsline {subsection}{\numberline {7.11.8}Per TF classes}{111}{subsection.7.11.8}
\contentsline {subsection}{\numberline {7.11.9}Per TF sub-classes}{111}{subsection.7.11.9}
\contentsline {chapter}{\numberline {8}Discussion}{113}{chapter.8}
\contentsline {chapter}{Discussions}{113}{chapter.8}
\vspace {\normalbaselineskip }
\contentsline {chapter}{\numberline {A}An appendix}{117}{appendix.A}
\contentsline {section}{\numberline {A.1}Supplementary figures}{117}{section.A.1}
\contentsline {chapter}{Bibliography}{149}{section*.66}
\contentsline {chapter}{Bibliography}{161}{appendix*.67}
\contentsline {chapter}{Curriculum Vitae}{163}{section*.68}

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