本文關(guān)鍵詞： 計算系統(tǒng)生物學 實體語法系統(tǒng) 優(yōu)化算法 作用機理解析 個體化 氨基酸組合設(shè)計　出處：《北京中醫(yī)藥大學》2017年碩士論文　論文類型：學位論文

【摘要】：背景:隨著社會經(jīng)濟的高速發(fā)展,生活水平的不斷提高,現(xiàn)代營養(yǎng)觀念已進入一新的時代:人(不一定是患者)應(yīng)該尋求一種帶有普遍性的、基礎(chǔ)性的、本質(zhì)性的營養(yǎng)物質(zhì),它適應(yīng)于疾病狀態(tài),也適應(yīng)于健康狀態(tài),尤其適應(yīng)于現(xiàn)在逐漸被人們認識的、客觀存在的亞健康狀態(tài)。這種營養(yǎng)物質(zhì)要起到增強體質(zhì)、加強抗體防御機制、提高生命質(zhì)量、延緩衰老的非特異性的作用。而氨基酸營養(yǎng)學從必需氨基酸與非必需氨基酸階段過渡到功能氨基酸階段,使得氨基酸在預防和治療代謝疾病包括肥胖、糖尿病、心血管障礙、無乳癥胎兒、后天生長遲緩、男女不孕不育、器官功能障礙和疾病感染、增強免疫力、延緩衰老等方面的作用日益凸顯,極大地刺激了氨基酸營養(yǎng)品的發(fā)展。目的:針對20種標準氨基酸,建立一套個體化的氨基酸營養(yǎng)品配方系統(tǒng),并能從整體的角度闡釋其發(fā)揮作用的分子機制,并基于作用機理解析的方法進行組合優(yōu)化,最終基于醫(yī)藥大數(shù)據(jù)的平臺建立個體化氨基酸組合的半定量設(shè)計系統(tǒng),實現(xiàn)用戶通過客戶端在線填寫關(guān)于癥狀的調(diào)查問卷,系統(tǒng)能自動給出相應(yīng)的氨基酸組合建議。方法:本課題主要通過計算系統(tǒng)生物學的方法來完成。(1)利用實驗室較為成熟的實體語法系統(tǒng),建立針對不同癥狀的氨基酸營養(yǎng)品配方系統(tǒng);(2)針對老人、孕婦、兒童等特殊人群,利用貪婪算法和二分圖進行氨基酸組合的優(yōu)化設(shè)計;(3)結(jié)合網(wǎng)絡(luò)藥理學的方法,以及保健品功能評價標準對氨基酸組合的作用進行作用機理解析;(4)基于作用機理解析的結(jié)果對氨基酸組合進行篩選與優(yōu)化;(5)基于醫(yī)藥大數(shù)據(jù)平臺,建立個體化氨基酸組合的的半定量設(shè)計系統(tǒng),將不同個體的不同癥狀以及不同癥狀程度量化,從而實現(xiàn)氨基酸組合的半定量設(shè)計。結(jié)果:(1)實現(xiàn)了針對1個癥狀,2個癥狀,3個癥狀的氨基酸自動配方系統(tǒng),充分發(fā)揮了氨基酸在人類健康方面的應(yīng)用;(2)針對老人、孕婦、兒童等特殊人群進行了氨基酸組合設(shè)計與優(yōu)化,從而完善了氨基酸自動配方系統(tǒng);(3)從網(wǎng)絡(luò)藥理學的角度對氨基酸調(diào)節(jié)免疫進行了作用機理解析,發(fā)現(xiàn)氨基酸及其代謝物調(diào)節(jié)免疫的分子路徑包括:①MAPK信號通路;②Fcε受體信號通路;③NF-κB轉(zhuǎn)錄因子活性的正向調(diào)控;④內(nèi)皮細胞生長因子信號通路;⑤TGF-β受體信號通路;⑥T細胞受體信號通路;⑦NO合酶的正向調(diào)控;⑧刺激的C型凝集素受體信號通路;⑨ERBB2信號通路;(4)以氨基酸免疫分子網(wǎng)絡(luò)為背景,以步長為評價指標,建立了免疫強度計算函數(shù)Score=∑in=1(∑jn=1fij(L1+L2)),對氨基酸調(diào)節(jié)免疫的強度進行了計算,最終發(fā)現(xiàn)分值排列在前三位的氨基酸為谷氨酸(score:24.67)、酪氨酸(score:20.83)、精氨酸(score:18.05),為氨基酸功能評價提供了新方法,為網(wǎng)絡(luò)藥理學的應(yīng)用提供了新思路;(5)通過系統(tǒng)打分函數(shù)對癥狀的分析,給出針對不同用戶的氨基酸組合推薦,實現(xiàn)了針對不同個體的不同癥狀以及不同癥狀程度的個體化氨基酸組合設(shè)計。結(jié)論:本研究利用計算系統(tǒng)生物學的方法,針對不同人群、不同癥狀、不同程度進行了個體化的氨基酸組合設(shè)計,并通過在線調(diào)查問卷的方式,使本研究得到實際應(yīng)用,為氨基酸營養(yǎng)品的應(yīng)用奠定了基礎(chǔ)。研究中初次探討了基于分子網(wǎng)絡(luò),氨基酸作用強度的評價,有效地減少了傳統(tǒng)實驗的時間與成本。進一步的研究將對研究結(jié)果進行實驗證明,優(yōu)化作用強度函數(shù)。
[Abstract]:Background: with the rapid development of social economy, the continuous improvement of living standards, the concept of modern nutrition has entered a new era: people (not necessarily patients) should seek a universal, fundamental, essential nutrients, it adapts to the disease state, but also adapt to the healthy state, especially for now is gradually recognized by people, the objective existence of the sub-health state. This kind of nutrients to enhance physical fitness, strengthen the antibody defense mechanism, improve the quality of life, non-specific anti-aging effect. And the amino acid nutrition from essential amino acid phase transition to the function of amino acids, the amino acids including obesity, diabetes, cardiovascular disorders in the prevention and treatment of metabolic diseases, agalactia fetal, postnatal growth retardation, male infertility, organ dysfunction and disease infection, enhance immunity, delay Aging has become increasingly prominent role, greatly stimulated the development of amino acid supplements. Objective: according to the 20 standard amino acids, amino acid nutrition formula system to establish a set of individual, and from the perspective of the whole play to explain the molecular mechanism of the effect, and based on the combination optimization method based on mechanism analysis, finally semi quantitative design system of medicine of big data platform for the establishment of individual amino acid combination, to achieve the user to fill in a questionnaire about symptoms through the client online system can automatically give the corresponding amino acid combination suggestions. Methods: This study mainly through methods of computational systems biology. (1) the use of laboratory mature entity grammar system according to the established formula system, amino acid nutrition symptoms; (2) for the elderly, pregnant women, children and other special groups, using the greedy algorithm and two points Figure optimized combination of amino acids; (3) combined with the method of network pharmacology, and to evaluate the effect of health care function of the standard amino acid combination mechanism analysis; (4) the mechanism analysis based on the results of amino acid combination screening and optimization; (5) medicine based on big data platform, the establishment of individual amino acid composition the semi quantitative design system, the different symptoms of different individuals and different degree of symptoms quantification, so as to realize the semi quantitative design of amino acid composition. Results: (1) to realize the 1 symptoms, 2 symptoms, automatic amino acid formula system of 3 symptoms, give full play to the use of amino acids in human health.; (2) for the elderly, pregnant women, children and other special groups were designed and optimized to improve the amino acid composition, amino acid automatic dispensing system; (3) Regulation of amino acids from the angle of network pharmacology The mechanism analysis of immunity, including amino acid and its metabolites found the molecular pathways regulating immunity: MAPK signaling pathway; Fc epsilon II receptor signaling pathway; the positive regulation of NF- kappa B transcription factor activity; the endothelial growth factor signaling pathway and TGF- signaling pathway; beta receptor; receptor signaling pathway and T positive cells; the regulation of NO synthase; C type lectin receptor signaling pathway and stimulation; ERBB2 signal pathway; (4) to the amino acid immune molecule network as the background, to step as the evaluation index, the calculation function of Score= in=1 immune strength establishment (sigma jn=1fij (L1+L2)), on the strength of the amino acid regulation of immune the final score calculation, found arranged in the top three of the amino acid glutamic acid (score:24.67), tyrosine (score:20.83), arginine (score:18.05), provides a new method for amino acid functional evaluation, application of network pharmacology Provides a new idea; (5) the symptom analysis system of scoring function, is given for the amino acid composition of different users, to realize the different symptoms of different individuals and different degree of symptoms of individual amino acid combination design. Conclusion: the method of using computational systems biology, for different groups, different symptoms, different the degree of amino acid combination design of individual, and through online questionnaires, this research has been applied, which laid the foundation for the application of amino acid nutrition. Studies are discussed for the first time based on molecular network, evaluation of strength of amino acids, can effectively reduce the time and cost of traditional experiment. Further research will be experimental results prove the optimization function, the intensity function.

【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R151

【參考文獻】

相關(guān)期刊論文 前10條

1 郭齊雅;于冬梅;俞丹;王尋;許曉麗;房sリ，

本文編號：1518399