Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits:
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
München
Verlag Dr. Hut
2015
|
| Edition: | 1. Auflage |
| Series: | Biologie
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | 132 Seiten Diagramme 21 cm x 14.8 cm, 309 g |
| ISBN: | 9783843923101 3843923108 |
Staff View
MARC
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| 100 | 1 | |a Prinz, Stephanie Jeanette |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits |c Stephanie Jeanette Prinz |
| 250 | |a 1. Auflage | ||
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| 338 | |b nc |2 rdacarrier | ||
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Record in the Search Index
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| adam_text | CONTENTS
1 INTRODUCTION 13
1.1 PHENOTYPIC INFORMATION 13
1.2 GENOTYPE-PHENOTYPE RELATIONS 14
1.3 DRUG ACTION 17
1.3.1 ADVERSE AND SIDE EFFECTS 18
1.3.2 DRUG TARGET DETECTION 19
1.3.3 VARIATION ON DRUG RESPONSE 21
1.4 PLIENOTYPE ONTOLOGIES AND SEMANTIC SIMILARITY APPROACHES 23
1.5 OBJECTIVE AND STRUCTURE OF THE THESIS 25
1.5.1 SYSTEMATIC ANALYSIS OF GENE PROPERTIES INFLUENCING ORGAN SYS
TEM PHENOTYPES 25
1.5.2 MOLECULAR AND CLINICAL CONNECTIONS BETWEEN DRUGS AND DISEASES 27
1.5.3 RELATIONSHIPS BETWEEN DRUGS AND GENES 27
2 RESULTS 29
2.1 TRANSLATION OF MOUSE PLIENOTYPE ANNOTATIONS TO THE MEDDRA TER
MINOLOGY 29
2.2 SYSTEMATIC ANALYSIS OF GENE PROPERTIES INFLUENCING ORGAN SYSTEM
PHENOTYPES 32
2.2.1 COMPARISON OF SOC HETEROGENEITY BETWEEN GENES, DISEASES
AND DRUGS 34
2.2.2 IMPACT OF NUMBER OF PERTURBED GENES ON DIVERSITY OF ORGAN
SYSTEM EFFECTS 35
2.2.3 SOC HETEROGENEITY OF SINGLE GENE PERTURBATIONS 37
2.2.4 ORGAN SYSTEM HETEROGENEITY DB 42
2.3 DISEASE-DRUG RELATIONSHIPS 44
2.3.1 PHENOTYPIC SIMILARITY OF INOLECULARLY RELATED DISEASES AND DRUGS
44
2.3.2 ENRICHMENT OF CLINICAL DISEASE-DRUG ASSOCIATIONS 46
2.4 DRUG-GENE RELATIONSHIPS 51
2.4.1 PHENOTYPIC SIMILARITY OF DRUGS AND GENES 51
2.4.2 BENCHMARKING OF PHENOTYPIC SIMILAR DRUG-GENE PAIRS 52
2.4.3 INTERACTIONS WITH BIOLOGICAIS 59
2.4.4 IN VITRO VALIDATION OF ESTABLISHED INTERACTIONS GO
2.4.5 EXPERIMENTAL VALIDATION OF NOVEL DRUG-TARGET, INTERACTION . . . 61
3 DISCUSSION 65
3.1 SYSTEMATIC ANALYSIS OF PHENOTYPIC INFORMATION 66
9
HTTP://D-NB.INFO/1078742499
3.1.1 SOC HETEROGENEITY 66
3.1.2 IMPLICATIONS FOR DRUG DESIGN 67
3.1.3 POLYPHARMACOLOGICAL PROPERTY OF DRUGS 68
3.2 DRUG-DISEASE SIMILARITY 70
3.3 DRUG-GENE SIMILARITY 71
3.3.1 DRUG-TARGET RELATIONSHIPS 71
3.3.2 INSIGHTS INTO DRUG SIDE EFFECTS 73
3.3.3 GENETIC VARIATION ON DRUG RESPONSES 74
3.3.4 MECHANISTIC EXPLANATIONS FOR NON-OBVIOUS ASSOCIATIONS .... 75
3.3.5 BIOLOGICALS 77
3.4 EXPERIMENTAL VALIDATION OF NOVEL DRUG-TARGET INTERACTION 78
3.5 LIMITATIONS 80
3.6 OUTLOOK 83
4 MATERIAL AND METHODS 85
4.1 PHENOTYPIC DATA 86
4.1.1 DRUG PHENOTYPIC INFORMATION (SIDE EFFECTS) 86
4.1.2 DISEASE PHENOTYPIC INFORMATION (SIGNS AND SYMPTOMS) .... 86
4.1.3 PHENOTYPIC INFORMATION FROM SINGLE GENE PERTURBATIONS IN MICE 87
4.1.4 MAPPING OF MAMMALIAN PHENOTYPE ONTOLOGY TERMS TO MED-
DRA 87
4.2 MEDDRA 88
4.3 SOC HETEROGENEITY 89
4.4 GENE PROPERTIES RELATED TO ORGAN SYSTEM PHENOTYPES 90
4.4.1 EXPRESSION DATA 90
4.4.2 TISSUE EXPRESSION HETEROGENEITY 90
4.4.3 BETWEENNESS CENTRALITY 90
4.4.4 ESSENTIAL GENES 91
4.4.5 CELLULAR LOCALIZATIONS OF GENE PRODUCTS 91
4.5 RELATIONSHIPS BETWEEN DRUGS, DISEASES AND GENES 92
4.5.1 DRUG TARGETS 92
4.5.2 DISEASE GENES 92
4.5.3 ADVERSE DRUG REACTION-DISEASE PAIRS 92
4.5.4 INDICATIONS AND CONTRAINDICATIONS 92
4.5.5 CLINICAL TRIALS 93
4.6 PHENOTYPIC SIMILARITY MEASURE 93
4.6.1 ADAPTION OF PHENOTYPIC SIMILARITY MEASURE OF DRUGS AND
MOUSE GENES TO THE POLYPHARINACOLOGICAL PROPERTY OF DRUGS . . 95
4.7 BENCHMARKING OF PHENOTYPIC SIMILARITY MEASURE 95
4.7.1 BENCHMARKING OF DRUG-DISEASE RELATIONSHIPS 97
4.7.2 BENCHMARKING OF DRUG-GENE RELATIONSHIPS 98
4.8 EXPERIMENTAL VALIDATION OF NOVEL DRUG-TARGET- INTERACTION 100
4.9 KNIME 102
4.10 CYTOSCAPE 102
10
5 SUMMARY 103
6 APPENDIX 105
C.L TABLES 105
G.2 SUPPLEMENTAL FIGURES 107
6.2.1 SOC HETEROGENEITY DISTRIBUTIONS OF HUMAN DISEASE GENE OR-
THOLOGUES OF ESSENTIAL AND NONESSENTIAL MOUSE GENES 107
G.2.2 ASSESSMENT OF THE EFFECT OF POTENTIAL ANNOTATION BIAS ON THE
CONCLUSIONS OF THE SOC HETEROGENEITY STUDY 108
6.2.3 PRECISION IN THE DETECTION OF DRUG-TARGET- INTERACTIONS 112
6.2.4 DATA DISTRIBUTION OF PHARMACOGENETIC ASSOCIATIONS 112
6.3 ABBREVIATIONS 117
GENE GLOSSARY 119
BIBLIOGRAPHY 121
11
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| any_adam_object | 1 |
| author | Prinz, Stephanie Jeanette |
| author_facet | Prinz, Stephanie Jeanette |
| author_role | aut |
| author_sort | Prinz, Stephanie Jeanette |
| author_variant | s j p sj sjp |
| building | Verbundindex |
| bvnumber | BV043221508 |
| classification_tum | BIO 750d MED 940d |
| ctrlnum | (OCoLC)951889316 (DE-599)BVBBV043221508 |
| dewey-full | 570 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 570 - Biology |
| dewey-raw | 570 |
| dewey-search | 570 |
| dewey-sort | 3570 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Medizin |
| edition | 1. Auflage |
| format | Thesis Book |
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| id | DE-604.BV043221508 |
| illustrated | Not Illustrated |
| indexdate | 2024-07-10T07:20:54Z |
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| isbn | 9783843923101 3843923108 |
| language | English |
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| physical | 132 Seiten Diagramme 21 cm x 14.8 cm, 309 g |
| publishDate | 2015 |
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| publisher | Verlag Dr. Hut |
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| series2 | Biologie |
| spelling | Prinz, Stephanie Jeanette Verfasser aut Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits Stephanie Jeanette Prinz 1. Auflage München Verlag Dr. Hut 2015 132 Seiten Diagramme 21 cm x 14.8 cm, 309 g txt rdacontent n rdamedia nc rdacarrier Biologie Dissertation Technische Universität München 2015 Genotyp (DE-588)4601328-3 gnd rswk-swf Maus (DE-588)4169148-9 gnd rswk-swf Symptom (DE-588)4184217-0 gnd rswk-swf Modellorganismus (DE-588)1028601360 gnd rswk-swf Pharmakologie (DE-588)4045687-0 gnd rswk-swf Phänotyp (DE-588)4248244-6 gnd rswk-swf Mouse Phenotypic Traits Genotype-Phenotype Relationships Drug Side Effects (DE-588)4113937-9 Hochschulschrift gnd-content Maus (DE-588)4169148-9 s Modellorganismus (DE-588)1028601360 s Genotyp (DE-588)4601328-3 s Phänotyp (DE-588)4248244-6 s Pharmakologie (DE-588)4045687-0 s Symptom (DE-588)4184217-0 s b DE-604 Verlag Dr. Hut (München) (DE-588)10174118-2 pbl DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028644396&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Prinz, Stephanie Jeanette Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits Genotyp (DE-588)4601328-3 gnd Maus (DE-588)4169148-9 gnd Symptom (DE-588)4184217-0 gnd Modellorganismus (DE-588)1028601360 gnd Pharmakologie (DE-588)4045687-0 gnd Phänotyp (DE-588)4248244-6 gnd |
| subject_GND | (DE-588)4601328-3 (DE-588)4169148-9 (DE-588)4184217-0 (DE-588)1028601360 (DE-588)4045687-0 (DE-588)4248244-6 (DE-588)4113937-9 |
| title | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits |
| title_auth | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits |
| title_exact_search | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits |
| title_full | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits Stephanie Jeanette Prinz |
| title_fullStr | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits Stephanie Jeanette Prinz |
| title_full_unstemmed | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits Stephanie Jeanette Prinz |
| title_short | Analysis of genotype-phenotype relationships based on drug side effects, disease symptoms and mouse phenotypic traits |
| title_sort | analysis of genotype phenotype relationships based on drug side effects disease symptoms and mouse phenotypic traits |
| topic | Genotyp (DE-588)4601328-3 gnd Maus (DE-588)4169148-9 gnd Symptom (DE-588)4184217-0 gnd Modellorganismus (DE-588)1028601360 gnd Pharmakologie (DE-588)4045687-0 gnd Phänotyp (DE-588)4248244-6 gnd |
| topic_facet | Genotyp Maus Symptom Modellorganismus Pharmakologie Phänotyp Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028644396&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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