Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Schlagworte: | |
| Online-Zugang: | kostenfrei https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20121220-1113756-0-0 Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. Sprache |
| Beschreibung: | IV, 163 S. Ill., graph. Darst. |
Internformat
MARC
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| 100 | 1 | |a Peis, Regina |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |c Regina Peis |
| 264 | 1 | |c 2012 | |
| 300 | |a IV, 163 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Zsfassung in dt. Sprache | ||
| 502 | |a München, Techn. Univ., Diss., 2012 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 776 | 0 | 8 | |i Erscheint auch als |n Online-Ausgabe |o urn:nbn:de:bvb:91-diss-20121220-1113756-0-0 |
| 856 | 4 | 1 | |u http://mediatum.ub.tum.de/node?id=1113756 |x Verlag |z kostenfrei |3 Volltext |
| 856 | 4 | |u https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20121220-1113756-0-0 |x Resolving-System | |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025932629&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 912 | |a ebook | ||
| 999 | |a oai:aleph.bib-bvb.de:BVB01-025932629 | ||
Datensatz im Suchindex
| _version_ | 1804150261841657856 |
|---|---|
| adam_text | IMAGE 1
CONTENTS
ABSTRACT 1
ZUSAINMENFASSUNG 3
1 INTRODUCTION 5
1.1 NEURODEGENERATION 5
1.1.1 ALZHEIMER S DISEASE 5
1.1.2 PARKINSON S DISEASE 6
1.1.3 STRESS AND DEPRESSION 7
1.2 REGULATORY MECHANISMS 8
1.2.1 TRANSCRIPTION FACTOR BINDING SITES 8
1.2.2 SINGLE NUCLEOTIDE POLYMORPHISMS 9
1.2.3 MICRORNAS 9
1.3 TFBS PROMOTER ANALYSIS (GENOMATIX) 10
1.4 MICROARRAY ANALYSIS 11
1.5 MICRORNA TARGET SITE PREDICTION AND DATABASES 12
1.6 BIOINFORMATICS ANALYSIS 13
1.6.1 STATISTICAL METHODS 13
1.6.2 SUPPORT VECTOR MACHINE AND RECURSIVE FEATURE ELIMINATION . . 14
1.6.3 BICLUSTERING 16
1.7 AIM OF THE THESIS 17
2 MATERIAL AND METHODS 1 9
2.1 BIOINFORMATICS IDENTIFICATION OF MODULES OF TRANSCRIPTION FACTOR
BINDING
SITES 19
2.1.1 IN SILICO PROMOTER ANALYSIS 19
2.1.2 MICROARRAY DATASETS 19
2.1.3 MULTIVARIATE ANALYSIS 20
2.1.4 ENRICHMENT ANALYSIS 22
2.1.5 LITERATURE MINING 22
2.2 MSVM-RFE AND BICLUST APPLICATION 23
2.2.1 DEPRESSION: HIGH AND LOW REACTIVITY 23
HTTP://D-NB.INFO/1036704726
IMAGE 2
CONTENTS
2.2.2 PARKINSON S DISEASE: DJ-1 KNOCKOUT 25
2.3 TFBS IN KEY GENES OF PARKINSON S DISEASE 26
2.3.1 TFBS PREDICTION IN PARKIN AND OPAL 26
2.3.2 MAPT AND SNCA - SNPS IN TFBSS 27
2.3.3 TFBSS PREDICTION IN PRKAA1, PRKAA2 AND PRKAG1 . . . 27 2.4
MICRORNAS BINDING TO ADAM10 28
2.4.1 MIRNA TARGET SITE PREDICTION DATABASES 28
2.4.2 MIRNA TARGET PREDICTION 28
2.4.3 EXTRACTION OF BEST MIRNA PREDICTIONS 29
2.4.4 STATISTICAL ANALYSIS 31
2.4.5 LITERATURE MINING AND PATHWAY ANALYSIS 31
2.4.6 EXPERIMENTAL VALIDATION 31
3 RESULTS 3 4
3.1 BIOINFORMATICS IDENTIFICATION OF MODULES OF TRANSCRIPTION FACTOR
BINDING
SITES : . . . 34
3.1.1 WORKFLOW 34
3.1.2 MODULES AND CONFIRMATIONS OF TFBSS AND AD-RISK GENES . . . 41
3.1.3 FIRST MODULE CTCF-EGRF-SP1F 45
3.1.4 SECOND MODULE CTCF-SP1F-ZBPF 45
3.1.5 ADDITIONAL INFORMATION OF THE THIRD MODULE KLFS-SP1F-ZBPF 46 3.2
MSVM-RFE AND BICLUST APPLICATION TO OTHER MICROARRAY DATASETS . . 47
3.2.1 HR VERSUS LR MICROARRAY 47
3.2.2 DJ-1 KNOCKOUT MICROARRAY 51
3.3 TFBSS IN KEY GENES OF PARKINSON S DISEASE 55
3.3.1 ATF4 BINDING SITE IN PARKIN PROMOTER 55
3.3.2 NFKB BINDING SITES IN THE PROMOTER OF OPAL 56
3.3.3 SNPS IN TFBSS OF MAPT AND SNCA PROMOTER AND FIRST INTRON 57 3.3.4
TFBSS IN PRKAA1, PRKAA2 AND PRKAG1 58
3.4 COMPUTATIONAL IDENTIFICATION AND EXPERIMENTAL VALIDATION OF
MICRORNAS BINDING TO ADAM10 61
3.4.1 MICRORNA PREDICTION 61
3.4.2 PREDICTION OF MIRNA TARGET GENES AND THEIR RELATION TO AD . 65
3.4.3 GENE ONTOLOGY 66
3.4.4 LITERATURE MINING 68
3.4.5 EXPERIMENTAL VALIDATION OF BIOINFORMATICALLY PREDICTED MIRNAS 69
4 DISCUSSION 7 1
4.1 EVALUATION OF BIOINFORMATICS APPROACH 71
II
IMAGE 3
CONTENTS
4.1.1 IDENTIFICATION OF TFBS MODULES IN AD KEY GENES AND COREGULATED
GENES 71
4.1.2 EVALUATION OF MSVM-RFE METHOD 72
4.1.3 ESTABLISHED WORKFLOW FOR MIRNA TARGET SITE PREDICTION . . . . 74
4.1.4 PREDICTION OF MIRNA TARGET GENES AND THEIR RELATION TO AD . 75
4.1.5 GWAS 76
4.2 REGULATORY NETWORK IN ALZHEIMER S DISEASE 77
4.2.1 TFBSS MODULES AND THEIR RELATION TO AD 77
4.2.2 MICRORNAS PREDICTED TO REGULATE ADAM10 83
4.3 REGULATORY NETWORK IN PARKINSON S DISEASE 89
4.3.1 CREB/ATF BINDING SITE IN PARKIN PROMOTER 89
4.3.2 SNPS MATCHING TFBSS IN MAPT AND SNCA REGULATORY REGION 89 4.3.3
COMMON TFBSS IN PRKAA1, PRKAA2 AND PRKAG1 . . . 90 4.3.4 PD RELATED
GENES IDENTIFIED IN A DJ-1 KNOCKOUT MOUSE MODEL 91 4.3.5 NFKB PATHWAY
RELATED TO PD 94
4.3.6 REGULATORY NETWORK OF PD GENES AS WELL AS PREDICTED AND VAL
IDATED TFBSS 95
4.4 REGULATORY NETWORK IN STRESS AND NEURODEGENERATION 97
4.4.1 DEPRESSION RELATED PATHWAYS IDENTIFIED IN HR/LR MOUSE MODELS 97
4.4.2 THE LINK BETWEEN DEPRESSION AND AD 98
4.4.3 THE ROLE OF MITOCHONDRIA IN DEPRESSION AND PD 100
4.4.4 MAPK PATHWAY ASSOCIATED TO AD AND DEPRESSION 101
4.5 HYPOTHETICAL REGULATORY MOLECULAR NETWORK IN NEURODEGENERATIVE DIS
EASES 103
5 CONCLUSION 1 0 6
BIBLIOGRAPHY 1 0 8
APPENDIX 1 3 1
LIST OF ABBREVIATIONS 131
LIST OF FIGURES 135
LIST OF TABLES 137
TARGET GENES OF TFBS MODULES 139
ENRICHMENT ANALYSIS 151
DJ-1 KNOCKOUT MICROARRAY: GENES ADJUSTED P-VALUE 0.35 153
MAPT AND SNCA - SNPS IN TFBSS 154
PREDICTED MICRORNA TARGET GENES 156
DANKSAGUNG 160
III
IMAGE 4
CONTENTS
LEBENSLAUF 162
IV
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| spelling | Peis, Regina Verfasser aut Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods Regina Peis 2012 IV, 163 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. Sprache München, Techn. Univ., Diss., 2012 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:91-diss-20121220-1113756-0-0 http://mediatum.ub.tum.de/node?id=1113756 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20121220-1113756-0-0 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025932629&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Peis, Regina Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |
| subject_GND | (DE-588)4113937-9 |
| title | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |
| title_auth | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |
| title_exact_search | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |
| title_full | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods Regina Peis |
| title_fullStr | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods Regina Peis |
| title_full_unstemmed | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods Regina Peis |
| title_short | Prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |
| title_sort | prediction of new regulatory molecular networks in neurodegenerative diseases with the help of bioinformatical methods |
| topic_facet | Hochschulschrift |
| url | http://mediatum.ub.tum.de/node?id=1113756 https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20121220-1113756-0-0 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025932629&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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