微型核醣核酸調控疾病關聯蛋白質複合體之整合資料庫

對於人類而言，很大部份的基因經歷選擇性剪接(Alternate Splicing)，之後轉譯成為不同的蛋白質Isoforms，轉譯後的蛋白質經由後修飾作用(Post Translational Modification , PTM)活化或抑制表達。生物過程大多由蛋白質交互作用(Protein-protein Interaction , PPI)調控，許多研究認為疾病的形成與isoforms的差異性表達有關。再者，PTM與PPI對於訊號傳遞機制都是必須的，而在此過程中某些的缺陷可能導致疾病的形成。在本研究中，我們整合了疾病關連的基因、蛋白質、Isoforms產物、PTM、基因本體論註解GO、胞器位置及PPI作為疾病研究的平台。此平台共包含39種疾病形式及47種胞器位置資訊，並使用傑卡德係數(Jaccard Index)量化任兩疾病包含相同蛋白質的比例，此傑卡德係數也許可以做為診斷之研究。本平台也提供一些胞器位置的特定PPI資訊，可進一步用Cytoscape視覺化呈現。我們使用肺癌的關聯基因作為案例研究，驗證如何使用本平台發掘進一步的疾病資訊。此外，本論文也辨識miRNA調控之蛋白質複合體。有些複合體由多個miRNA所調控。若某複合體執行特定的生物功能，我們可以預期這些miRNA所調控的複合體也許會導致可觀察的表現型效應。此疾病網站的網址: http://bioinfo.csie.nfu.edu.tw/Dis/index.php.

關鍵字

人類疾病；選擇性剪接；後修飾作用；胞器位置；蛋白質交互作用PPI ；蛋白質複合體； miRNA微型核醣核酸

並列摘要

In human, a large portion of genes undergoes alternative splicing then translates into different protein isoforms. Translated proteins are activated or repressed through post-translational modification (PTM). Biological processes are mediated by protein-protein interaction (PPI). Many research studies suggested that disease formation involves differential expression of isoforms. Furthermore, both of PTM and PPI are essential for the signal transduction mechanism where defects in such process may lead to disease formation. In this work, disease-associated genes, proteins, alternative products, PTM, Gene Ontology (GO) annotations, subcellular localization and PPI information are integrated to provide a sophisticated platform for disease studies. A total of 39 disease types and 47 subcellular localizations information are included in the platform. This platform also provided an index, Jaccard index; to quantify the portion of common proteins involved for any two of the diseases, which may be useful for comorbidity study. A few subcellular localization specific PPI information are available in Cytoscape display format. Using lung cancer associated genes as a case study, we demonstrate how to use the web server resource to discover further disease information. miRNA-regulated protein complexes were identified. Certain complexes are highly regulated by miRNAs. Given that a complex can perform specific biological function, one may expect miRNA-regulated complex may result in observed phenotypic effects. A web-based platform has been set up to display the results; it can be accessed at http://bioinfo.csie.nfu.edu.tw/Dis/index.php.

並列關鍵字

Human disease ； alternative splicing ； post-translational modification ； subcellular localization ； protein-protein interaction ； protein complex ； miRNA

參考文獻

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[6] Esquela-Kerscher A, Slack F.J., (2006).Oncomirs – microRNAs with a role in cancer. Nature Reviews Cancer, 6, pp. 259-269

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[8] Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. (2005). Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature, 433, pp. 769-773

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微型核醣核酸調控疾病關聯蛋白質複合體之整合資料庫

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