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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 阮雪芬(Hsueh-Fen Juan) | |
| dc.contributor.author | Kai-Pu Chen | en |
| dc.contributor.author | 陳凱普 | zh_TW |
| dc.date.accessioned | 2021-05-13T08:40:57Z | - |
| dc.date.available | 2018-02-24 | |
| dc.date.available | 2021-05-13T08:40:57Z | - |
| dc.date.copyright | 2016-02-24 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-01-21 | |
| dc.identifier.citation | 1. Merlini, L., et al., Scoliosis in spinal muscular atrophy: natural history and management. Dev Med Child Neurol, 1989. 31(4): p. 501-8.
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Gabanella, F., et al., Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One, 2007. 2(9): p. e921. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/4037 | - |
| dc.description.abstract | 脊髓型肌肉萎縮症和脊髓側索硬化症是由運動神經元退化及伴隨肌肉萎縮的致命性疾病，雖然兩者的致病突變基因不同，但兩者間有共同表現的症狀。為了探討兩疾病間可能的共同致病機制，我們分別建立了脊髓型肌肉萎縮症和脊髓側索硬化症的差異化蛋白質共表現網絡(DCPINs)。我們在此利用gene ontology將有差異的蛋白質網絡做功能上的分群，接著我們討論講疾病間模組的關係性。藉由結合靜態的蛋白質網絡以及mRNA的基因表現量的分析，我們找到了錯誤的蛋白質交互作用可能會導致細胞中鈣離子循環失控。我們發現對抗鈣離子及熱所導致的細胞壓力有關的蛋白質交互作用。此外，我們也找到和蛋白質ubiquitination與proteasome降解相關的蛋白質交互作用。同時我們進一步發現和ATP生成相關之缺失的蛋白質作用也出現在粒線體複合體I, III及V，並加以進行探討。參與RNA剪接作用的蛋白質snRNPs的一部分組成蛋白-七環Sm蛋白，也在兩個疾病中被發現有較低的相關性並可能進階導致snRNPs生成的失敗。在本篇論文中，我們認為這兩疾病的肌肉中所產生的細胞壓力，於疾病發生時可能扮演了很重要的角色。 | zh_TW |
| dc.description.abstract | Spinal muscular atrophy (SMA) and¬ amyotrophic lateral sclerosis (ALS) are two devastating diseases caused by motor neuron degeneration and accompanied with muscle weakness. Though the mutated genes causing SMA and ALS are different, some of the phenotypes are the same in both diseases. To understand the possibility of common and dysregulated mechanisms between SMA and ALS, differentially co-expressed protein interaction networks (DCPINs) are constructed in SMA and ALS respectively. Gene ontology analysis is applied to help us realize the functions of these disrupted protein interactions. Both SMA and ALS related modules were further isolated and discussed. By means of integrative analysis using static protein interaction network and the microarray gene expression profiles, perturbed protein interactions involving in calcium cycling were found in this study. The possible responses against stress caused by calcium and thermogenesis were also discovered. Furthermore, we identified the protein interactions associated with protein ubiquitination and proteasomal degradation. Additionally, we found the defective protein interactions engaged in path of ATP synthesis of mitochondrial protein complex I, III and V and have further discussion. Proteins involved in RNA splicing were also found and showed the potential deformity in heptameric ring consisted of Sm proteins during formation of snRNPs. In this study, we suggest that the stress induced in the muscle of SMA and ALS might play an important role in the pathology of both diseases. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-13T08:40:57Z (GMT). No. of bitstreams: 1 ntu-105-R02945027-1.pdf: 4498933 bytes, checksum: 8ab6274d5c52c554501ed379d30eb1b7 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員會審定書….……………………………………...………….................................i
誌謝………………………..………………………………………………………………..ii 中文摘要….………….……….………….…………………...............................................iii Abstract…...………….……………………………………..….…..…..………….…..........iv Contents…………………………………………………….………….……………...........vi List of Figures…………………………………………………………..……………...….viii List of Tables……………………………………………………………….……….………x Chapter 1 Introduction…………………….…………………...…………………….……1 1.1 Motor neuron disease……………….……..………………………………………….1 1.1.1 Spinal muscular atrophy…………………….……..……….………………...….1 1.1.2 Amyotrophic lateral sclerosis……………………..….……….………...……….2 1.1.3 Interaction between SMA and ALS…....……….……….………..…….…..……3 1.2 Protein interaction network………………..…………………………………...……..3 1.3 Microarray analysis……………………………………………………………..…….4 1.4 Integrative analysis of protein interaction network…………………………..…........4 Chapter 2 Materials and methods.….…………………….…............................................6 2.1 Human protein interaction network……………………………………………..........6 2.2 mRNA expression profiles………………………………….……………...…………6 2.3 Construction of differentially co-expressed PIN ………...…………..….…..….……7 2.3.1 Spearman’s correlation coefficient…………………………………....................7 2.3.2 Differentially co-expressed PIN …………...………………………….…..…….7 2.4 Identification of disease-specific functional modules………………..……..….….….8 2.4.1 Gene ontology…………………………………….………..…….………………8 2.4.2 Hypergeometric test………..……………………………………….……………9 2.4.3 Enrichment map………………………….……………………..……...……….10 2.4.4 Modules……………………….………………………………….………..…....10 2.5 Network properties…………………………………….…………....……………….10 2.5.1 Degree………………………………………………………………...………...10 2.5.2 Clustering coefficient…………………………………….………………..........11 2.5.3 Betweenness centrality………………………………...………………………..11 2.5.4 Closeness centrality………………………………………...…………………..11 Chapter 3 Results………………………………………………………..…………….….12 3.1 Identification of dysregulated PPIs in SMA and ALS ………………..……….……12 3.2 Recognitions of enriched modules………………………………………..…….…...13 Chapter 4 Discussion………………………………………………………………...…...15 4.1 ‘Muscle system process’…………………………………………………………….15 4.2 ‘Proteasome-mediated ubiquitin-dependent protein catabolic process’…...………..16 4.3 ‘Respiratory electron transport chain’…………………………………..……...…...18 4.4 ‘RNA splicing’……………………………………………………………………....20 Chapter 5 Conclusion…………………………………………………………..…….…..22 References…………………………………………………………………………...……..23 Figures…………………………………………………………………………………...…29 Tables…………………..……………...……………………………………………….…..43 | |
| dc.language.iso | en | |
| dc.subject | 和RNA的剪接作用 | zh_TW |
| dc.subject | 脊髓型肌肉萎縮症 | zh_TW |
| dc.subject | 脊髓側索硬化症 | zh_TW |
| dc.subject | 差異化蛋白質共表現網絡 | zh_TW |
| dc.subject | 壓力 | zh_TW |
| dc.subject | 鈣離子的失調 | zh_TW |
| dc.subject | ubiquitination | zh_TW |
| dc.subject | proteasome的蛋白質降解 | zh_TW |
| dc.subject | ATP | zh_TW |
| dc.subject | proteasomal degradation | en |
| dc.subject | ATP | en |
| dc.subject | SMA | en |
| dc.subject | ALS | en |
| dc.subject | DCPINs | en |
| dc.subject | module | en |
| dc.subject | stress | en |
| dc.subject | calcium dysregulation | en |
| dc.subject | ubiquitination | en |
| dc.subject | and RNA splicing | en |
| dc.title | 藉由蛋白質網絡探討脊髓肌肉萎縮症和脊髓側索硬化症的關聯性 | zh_TW |
| dc.title | Comparative analysis of condition-specific protein interaction networks between spinal muscular atrophy and amyotrophic lateral sclerosis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 歐陽彥正(Yen-Jen Oyang) | |
| dc.contributor.oralexamcommittee | 黃宣誠(Hsuan-Cheng Huang),林振慶(Chen-Ching Lin),王禹超(Yu-Chao Wang) | |
| dc.subject.keyword | 脊髓型肌肉萎縮症,脊髓側索硬化症,差異化蛋白質共表現網絡,壓力,鈣離子的失調,ubiquitination,proteasome的蛋白質降解,ATP,和RNA的剪接作用, | zh_TW |
| dc.subject.keyword | SMA,ALS,DCPINs,module,stress,calcium dysregulation,ubiquitination,proteasomal degradation,ATP,and RNA splicing, | en |
| dc.relation.page | 82 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2016-01-22 | |
| dc.contributor.author-college | 電機資訊學院 | zh_TW |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | zh_TW |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
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