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    題名: 以修格連氏症患者血清內代謝體導入機器學習方法整合生物標記組合之診斷效能
    Introducing Sjogren’s Syndrome Serum Derived Metabolomic Data into Machine Learning Methods to Incorporate Diagnostic Performance of Biomarkers
    作者: 洪翔譯
    Hong, Xiang-Yi
    貢獻者: 醫學檢驗暨生物技術學系碩士在職專班
    林景堉
    關鍵詞: 修格連氏症候群;代謝體學;液相層析串聯式質譜儀系統
    Sjogren's syndrome;Metabolomics;Liquid chromatography tandem mass spectrometry
    日期: 2023-01-10
    上傳時間: 2024-01-22 13:23:19 (UTC+8)
    摘要: 修格連氏症候群(Sjogren’s Syndrome)是屬於一種慢性發炎的自體免疫疾病。該病會造成人體外分泌腺:淚腺、唾液腺為主的破壞。導致修格連氏症候群患者一般臨床可分為兩種型態:原發性(Primary)以及續發性(Secondary)。倘若只有口乾及眼乾的症狀臨床則稱之為-原發性。繼發性-則除了口乾及眼乾等症狀以外,還伴隨其他相關自體免疫疾病,如:紅斑性狼瘡、類風濕性關節炎、多發性肌炎等症狀。該疾病以流行病學來說: 修格連氏症好發於40-60歲更年期後的女性,不過男性或年輕女性、甚至小孩也是發病的機率,若以性別分布來說:女性與男性發生的比率為9:1。
    至今代謝體學探索生命體系中所有小分子代謝物的變異,藉以呈現生命體因應生理病理上的變化,係以高通量方式針對多樣代謝物進行定性與定量及其自體免疫疾病之應用甚廣,但以多重反應監測絕對定量進行修格連氏症候群代謝體學研究甚少。因此本研究的目的是-探討原發性修格連氏症病人之血液離心處理後的血清與健康對照組(Healthy control,HC)進一步驗證表現量有差異的疏水性或親水性代謝物能否成為檢測此疾病之血清生物標記並探討代謝物對修格連氏症的角色。並且建立一套利用液相層析串質譜儀(LC-MS/MS)的分析方法。利用該代謝體表現量之顯著差異進行接收操作特徵曲線分析,計算曲線下面積獲得良好的分辨率。
    藉此能提出以液相層析串聯四極桿飛行質譜儀分析、MRM MS(Multiple reaction monitoring mass spectrometry)研究,導入機器學習模組,使其驗證出血清生物標記用於檢測原發性-修格連氏症候群。
    Sjogren's syndrome is a chronic inflammatory autoimmune disease。The disease will cause the destruction of exocrine glands:lacrimal and salivary glands。Sjogren's syndrome can generally be divided into two types: primary and secondary。Primary symptoms are only dry mouth and dry eyes,while secondary symptoms are accompanied by other autoimmune diseases,such as lupus erythematosus、rheumatoid arthritis、polymyalgia。
    In terms of epidemiology: Sjogren's syndrome is more common in women after menopause between the ages of 40 and 60。But men、young women and even children have the possibility of developing the disease。Generally,the ratio of women to men is 9:1。
    Metabolomics explores the variation of all small molecule metabolites in the living system,so as to show the physiological and pathological changes of living organisms。But there are very few metabolomic studies of Sjogren's syndrome with absolute quantification of multiple reaction monitoring。Therefore,the purpose of this study is to further verify whether the hydrophobic or hydrophilic metabolites with different expression levels can be used to detect the primary Serum biomarkers of Sjogren's disease and explore the role of metabolites in Sjogren's disease。And using liquid chromatography tandem mass spectrometer (LC-MS/MS) analysis method,using the significant difference in metabolite expression to analyze the receiver operating characteristic curve,calculate the area under the curve to obtain a good resolution。
    In this way,it can be proposed to develop the detection technology for the purpose of ultra-high performance liquid chromatography tandem quadrupole flying mass spectrometer analysis,MRM/ MS (Multiple reaction monitoring mass spectrometry) research and the development of laboratory developed test technology (LDTs)。Import a machine learning module to validate Serum biomarkers in primary Sjogren's disease。
    描述: 碩士
    指導教授:林景堉
    委員:張哲菖
    委員:莊禮聰
    委員:林景堉
    資料類型: thesis
    顯示於類別:[醫學檢驗暨生物技術學系所] 博碩士論文

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