An investigation of microRNA target regulation mechanisms using an integrative approach:
Gespeichert in:
| Beteilige Person: | |
|---|---|
| Format: | Hochschulschrift/Dissertation Buch |
| Sprache: | Englisch |
| Veröffentlicht: |
Berlin
Logos Verlag
[2015]
|
| Schlagwörter: | |
| Links: | https://d-nb.info/1072090902/04 http://deposit.dnb.de/cgi-bin/dokserv?id=5288836&prov=M&dok_var=1&dok_ext=htm http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032635768&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| Umfang: | XIV, 185 Seiten Illustrationen, Diagramme 21 cm |
| ISBN: | 9783832540050 3832540059 |
Internformat
MARC
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Datensatz im Suchindex
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|---|---|
| adam_text | CONTENTS
ABSTRACT I
ACKNOWLEDGEMENTS V
CONTENTS VII
LIST OF FIGURES IX
LIST OF TABLES XI
ABBREVIATIONS XIII
1 INTRODUCTION 1
1.1 MOTIVATION 2
.2 OUTLINE OF THE THESIS 2
1.3 NON-CODING RNA GENES 4
1.4 MIRNAS 6
1.4.1 MIRNA GENOMIC MAKEUP AND REGULATION 7
1.4.2 MIRNA BIOGENESIS 8
1.4.3 MIRNA TARGET REGULATION 10
1 4.4 MIRNAS IN HUMAN PATHOLOGIES 14
2 A COMPARATIVE ANALYSIS OF METHODS IN COMPUTATIONAL MIRNA BIOLOGY 17
2.1 BIOMFORMATICS APPROACHES 18
2.1.1 COMPUTATIONAL IDENTIFICATION OF MIRNA GENES 18
2.1.2 APPROACHES FOR THE PREDICTION AND ANALYSIS OF MIRNA TARGET GENES
20
2.1.3 STRUCTURE PREDICTION AND ANALYSIS OF SINGLE AND INTERACTING RNA
STRANDS 23
2.1.4 MIRNA EXPRESSION ANALYSIS AND FUNCTIONAL CHARACTERIZATION 28
2.1.5 MIRNA WEB RESOURCES 30
2.2 SYSTEMS BIOLOGY APPROACHES 32
2.2.1 MODELLING MIRNA TARGET REGULATION C 33
2.2.2 MIRNA REGULATORY NETWORK MODELLING 36
2.2.3 MODELLING THE ROLE OF MIRNAS IN PATHOGENESIS AND DISEASE
PROGRESSION 41
3 RECONSTRUCTION AND ANALYSIS OF NETWORKS REGULATING MIRNA TARGET HUBS
43
3.2 MOTIVATION FOR AND DESIGN OF THE CATH WORKFLOW 44
3.3 RESEARCH STRATEGY 47
3 3.1 DATA INTEGRATION 47
3 3.2 CONFIDENCE SCORES FOR MOLECULAR INTERACTION DATA 49
3.3.3 NETWORK RECONSTRUCTION AND ANALYSIS 52
3.3.4 DERIVATION OF A KINETIC MODEL 54
3.3.5 EXPERIMENTAL VALIDATION 55
3 4 CASE STUDY 56
3 4.1 MOLECULAR INTERACTION NETWORK DISPLAYS SOPHISTICATED CDKN1A
REGULATION 56
3.4.2 A PREDICTIVE MODEL OF CDKNIA REGULATION BY MULTIPLE MIRNAS 60
3.4.3 THREE MODES OF COMBINATORIAL TARGET REGULATION 62
3.4.4 WET LAB EXPERIMENTS VALIDATE MODEL STRUCTURE 65
3 4.5 MODEL SIMULATIONS PREDICT PROCESSES-SPECIFIC CDKNIA EXPRESSION 66
3.4.6 PREDICTION OF CDKNIA EXPRESSION FOR DIFFERENT TISSUES 68
3.4 7 MODULATION OF MIRNA COOPERATIVITY INFLUENCES TARGET REPRESSION
EFFICIENCY 68
VII
HTTP://D-NB.INFO/1072090902
3.4.8 MIRNA COOPERATIVITY TO ENHANCE NOISE BUFFERING 70
3.5 SUMMARY 70
3.5.1 CONFIDENCE SCORES FOR MOLECULAR INTERACTIONS 72
3.5.2 MATHEMATICAL MODELS OF MIRNA-TARGET REGULATION 72
3.5.3 MECHANISMS OF MIRNA-TARGET REGULATION 73
3.5.4 GENERALIZATION OF THE CATH WORKFLOW 76
4 PREDICTION AND VALIDATION OF COOPERATING MIRNAS AND THEIR MUTUAL
TARGETS 79
4.1 BACKGROUND 80
4.2 RESEARCH STRATEGY 83
4.2.1 PREDICTED AND VALIDATED MIRNA TARGET INTERACTIONS 83
4.2.2 SECONDARY STRUCTURE AND MINIMUM FREE ENERGY PREDICTION 84
4.2.3 TERTIARY STRUCTURE MODELLING AND MOLECULAR DYNAMICS SIMULATIONS 85
4.2.4 PREDICTION OF COMPLEX EQUILIBRIUM CONCENTRATIONS 88
425 A MECHANISTIC
MODEL
OF SYNERGISTIC
TARGET
REGULATION 88
4.2.6 DATA SHARING 92
4.3 CASE STUDY 93
4.3.1 IDENTIFICATION OF MIRNA TARGET SITES 93
4.3.2 COOPERATIVE TARGET REGULATION MAY EFFECT MOST HUMAN PROTEIN CODING
GENES 94
4.3.3 TRIPLEXES WITH CONSERVED TARGET SITES HAVE LOWER BINDING
AFFINITIES 95
4.3.4 CANONICAL RNA TRIPLEXES FORM THE THERMODYNAMICALLY MOST STABLE
STRUCTURES 96
4.3.5 MDS CAN DISCRIMINATE THERMODYNAMICALLY UNSTABLE TRIPLEXES 99
4.3.6 TRIPLEX FORMATION DEPENDS ON EQUILIBRIUM PROBABILITY DISTRIBUTION
103
4.3 7 SIMULATIONS OF MIRNA COOPERATIVITY REVEAL LANDSCAPES OF TARGET
REPRESSION 105
4.3.8 A DATABASE OF HUMAN RNA TRIPLEXES 108
4.4 SYNTHESIS OF RESULTS 109
4.4.1 WAYS TO NARROW DOWN HIGH-CONFIDENCE RNA TRIPLEXES 110
4 4 2 WHAT CAN BE LEARNED FROM 2D AND 3D MODELS OF RNA TNPLEX
STRUCTURES? 112
4 4 3 TIME CONSUMING BUT VALUABLE MDS 113
4 4 4 TARGET REGULATION EFFICIENCY REVISITED 114
4 4.5 COOPERATIVE TARGET REGULATION - A PHENOMENON WITH RELEVANCE FOR
CANCER? 114
4.4.6 GENERAL REMARKS 115
5 DISCUSSION 117
5.1 EXPLORATION OF A NEW CLASS OF NCRNA 118
5.2 THE NECESSITY OF AN INTEGRATIVE BIOINFORMATICS AND SYSTEMS BIOLOGY
APPROACH 119
5 3 OUTLOOK 121
5.4 CONCLUSION 122
APPENDIX 123
REFERENCES 159
CURRICULUM VITAE 177
PUBLICATIONS 181
THESES 185
VIII
|
| any_adam_object | 1 |
| author | Schmitz, Ulf 1978- |
| author_GND | (DE-588)1073935299 |
| author_facet | Schmitz, Ulf 1978- |
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| dewey-full | 572.865011 |
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| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572.865011 |
| dewey-search | 572.865011 |
| dewey-sort | 3572.865011 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Thesis Book |
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| indexdate | 2024-12-20T19:13:32Z |
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| language | English |
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| physical | XIV, 185 Seiten Illustrationen, Diagramme 21 cm |
| publishDate | 2015 |
| publishDateSearch | 2015 |
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| publisher | Logos Verlag |
| record_format | marc |
| spellingShingle | Schmitz, Ulf 1978- An investigation of microRNA target regulation mechanisms using an integrative approach Systembiologie (DE-588)4809615-5 gnd Computersimulation (DE-588)4148259-1 gnd Posttranskriptionelle Regulation (DE-588)4356177-9 gnd miRNS (DE-588)7736808-3 gnd |
| subject_GND | (DE-588)4809615-5 (DE-588)4148259-1 (DE-588)4356177-9 (DE-588)7736808-3 (DE-588)4113937-9 |
| title | An investigation of microRNA target regulation mechanisms using an integrative approach |
| title_auth | An investigation of microRNA target regulation mechanisms using an integrative approach |
| title_exact_search | An investigation of microRNA target regulation mechanisms using an integrative approach |
| title_full | An investigation of microRNA target regulation mechanisms using an integrative approach vorgelegt von Ulf Schmitz |
| title_fullStr | An investigation of microRNA target regulation mechanisms using an integrative approach vorgelegt von Ulf Schmitz |
| title_full_unstemmed | An investigation of microRNA target regulation mechanisms using an integrative approach vorgelegt von Ulf Schmitz |
| title_short | An investigation of microRNA target regulation mechanisms using an integrative approach |
| title_sort | an investigation of microrna target regulation mechanisms using an integrative approach |
| topic | Systembiologie (DE-588)4809615-5 gnd Computersimulation (DE-588)4148259-1 gnd Posttranskriptionelle Regulation (DE-588)4356177-9 gnd miRNS (DE-588)7736808-3 gnd |
| topic_facet | Systembiologie Computersimulation Posttranskriptionelle Regulation miRNS Hochschulschrift |
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