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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 高成炎 | |
| dc.contributor.author | Ko-Chun Yang | en |
| dc.contributor.author | 楊克鈞 | zh_TW |
| dc.date.accessioned | 2021-06-16T08:13:22Z | - |
| dc.date.available | 2016-04-08 | |
| dc.date.copyright | 2014-03-21 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-02-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58386 | - |
| dc.description.abstract | 由於開發新藥物成本高、研發時程長，舊藥新用為生醫資訊之研究方向之一。本研究利用ONCOMINE資料庫內的癌症基因表現差異，配合Connectivity Map內的不同藥物處理細胞株產生之基因表現差異資料，藉由Connectivity Map評估具有潛力之藥物，並進一步利用DrugBank、POINeT去分析這些藥物之作用路徑、作用標靶、蛋白質交互作用，以得到較可靠之藥物供後續生物實驗測試。
研究中疾病選擇攝護腺癌，經由ONCOMINE資料庫中取不同門檻值之高低表現量基因，分別輸入Connectivity Map以得到具潛力藥物，共獲得12項候選藥物，其中5項屬於癌症治療用藥(vorinostat，皮膚淋巴癌。tanespimycin、alvespimycin，HSP-90抑制劑。camptothecin、fulvestrant，乳癌)，以及1項(alfuzosin)屬於前列腺肥大用藥。查詢候選藥物的Drug Bank直接作用標靶蛋白質，並以POINeT分析疾病高低表現量基因與藥物標靶蛋白。具有S3 排名者有vorinostat之HDAC、HDAC2和fulvestrant之ESR1三個標靶蛋白，但相對於疾病高低表現量基因網路上節點排名為低，表示藥物可能具有療效，但藥物對於整體蛋白質交互作用網路的影響可能較小。 | zh_TW |
| dc.description.abstract | Due to the high cost of money and time for new drug development, new application for old drugs is one of the critical directions in bioinformatics research. In the present study, cancer gene expression differences accessed via the database ONCOMINE along with the differences in gene expression by different drugs dealing with cell lines within the Connectivity Map were utilized. Based on the potential drugs assessed by Connectivity Map, DrugBank and POINeT were used to analyze the pathways of drugs and their therapeutic targets as well as protein interactions in order to obtain putative candidate drugs for follow-up biological testing experiments.
Prostate cancer was chosen in this study, and variant volume of gene expressions in different threshold levels retreived via ONCOMINE were keyed in Connectivity Map to obtain 12 potential drug candidates, of which five are associated with cancer treatment medicine (vorinostat, cutaneous lymphoma; tanespimycin, alvespimycin, HSP-90 inhibitors; camptothecin ,fulvestrant, breast cancer), and 1 (alfuzosin) is prostate medication. Querying drug candidates of direct target proteins in Drug Bank and analyzing the performance of the volume of disease genes and drug target proteins using POINeT, the results show as follows: three target proteins are vorinostat of HDAC1, HDAC2 and fulvestrant of ESR1, but the scores of gene network nodes were low relative to the level of performance volume of disease. Thus, it is indicated that the drugs may have effects but may have relatively small impact concerning the overall protein-protein interaction network. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T08:13:22Z (GMT). No. of bitstreams: 1 ntu-103-R97945020-1.pdf: 3888868 bytes, checksum: 65bcb7796b96a1c7df682e49fa13d907 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 誌謝 i
中文摘要 ii 英文摘要 iii 第一章 緒論 1 1.1研究背景 1 1.2研究動機與目的 1 第二章 文獻探討 3 2.1基因表現資料庫 3 2.2疾病相關基因資料庫 4 2.3藥物資料庫 7 2.4藥物反應資料庫 7 2.5蛋白質交互作用資料庫 8 2.6生物註解資料庫 9 第三章 研究流程與方法 12 3.1建立ONCOMINE差異表現基因之蛋白質交互作用網路 13 3.2 Connectivity Map候選藥物分析並建立蛋白質交互作用網路 13 3.3分析已知攝護腺癌藥物標靶蛋白之蛋白質交互作用網路 13 3.4建立攝護腺癌相關基因之蛋白質交互作用網路 14 3.4蛋白質網路分析與藥物評估應用潛力 14 第四章 結果 15 4.1 ONCOMINE攝護腺癌高低表現量基因 15 4.2 Connecttivity Map候選藥物分析 16 4.3 POINeT蛋白質交互作用網路分析 20 4.4攝護腺癌藥物分析 25 第五章 討論 28 第六章 結論 30 參考文獻 31 附錄 35 | |
| dc.language.iso | zh-TW | |
| dc.title | 基於疾病相關微陣基因群的候選藥物評估 | zh_TW |
| dc.title | Putative Candidate Drugs Based on Disease-related Microarray Genes by Protein-protein Interaction Network | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 朱學亭,李盛安 | |
| dc.subject.keyword | 新適應症,候選藥物,微陣基因,蛋白質交互作用,生物資訊, | zh_TW |
| dc.subject.keyword | New Indication,Candidate Drug,Microarray Gene,Protein-Protein Interaction,Bioinformatics, | en |
| dc.relation.page | 41 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-02-14 | |
| 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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