矩陣填充算法及其在流感病毒抗原性研究中的運用
本文選題:低秩矩陣填充 + 抗原距離; 參考:《浙江理工大學(xué)》2017年碩士論文
【摘要】:流行性感冒是流感病毒引起的急性呼吸道感染疾病,它傳染性強(qiáng)、傳播速度快,流感的預(yù)防一直受到世界各國的高度重視。目前,血凝素抑制試驗(HI)是獲得流感病毒抗原性特征的常規(guī)手段之一,但是,由于受到實驗條件的干擾和限制,導(dǎo)致有些數(shù)據(jù)不準(zhǔn)或有些數(shù)據(jù)無法得到,為了獲取可靠的、完整的血凝素抑制試驗數(shù)據(jù),本文基于低秩矩陣填充算法,提出了一種新的融合了生物信息的低秩矩陣填充算法,帶邊信息的生物矩陣填充算法(BMCSI)。本文應(yīng)用這個模型到1968-2003年的H3N2流感病毒數(shù)據(jù),通過將HA蛋白序列的相似性信息整合進(jìn)矩陣填充模型,用來預(yù)測流感病毒的抗原性。首先對血凝素抑制試驗數(shù)據(jù)中已有的低反應(yīng)數(shù)據(jù)進(jìn)行了重估計,對缺失的數(shù)據(jù)進(jìn)行了恢復(fù)。通過10倍交叉驗證法評估該算法,與已有的計算方法比較,該算法的均方根誤差減少了37%。利用這些重估后的數(shù)據(jù)構(gòu)造抗原圖和遺傳圖,結(jié)果顯示H3N2流感病毒的抗原進(jìn)化圖呈“S”型,遺傳進(jìn)化圖呈半圓型。進(jìn)一步地,本研究通過分析H3N2流感病毒的遺傳進(jìn)化與抗原進(jìn)化之間的關(guān)系,發(fā)現(xiàn)遺傳距離與抗原距離的斯皮爾曼相關(guān)系數(shù)是0.83,此結(jié)果說明遺傳進(jìn)化與抗原進(jìn)化之間雖然有局部差異但全局具有高度的一致性。本文根據(jù)上述算法BMCSI提出了一種選擇疫苗株的方法,并對歷史疫苗株的選擇進(jìn)行了評估。另外,我們還將這個模型運用到CCLE中491種癌細(xì)胞系與24種抗癌藥物反應(yīng)的敏感性數(shù)據(jù)上,利用矩陣的行和列之間的相關(guān)性以及基因表達(dá)特征來預(yù)測抗癌藥物敏感值,然后通過抗癌藥物敏感性數(shù)據(jù)尋找與藥物敏感性關(guān)聯(lián)的基因。
[Abstract]:Influenza is an acute respiratory infection caused by influenza virus. At present, hemagglutinin inhibition test (HIH) is one of the conventional methods to obtain the antigenicity characteristics of influenza virus. However, due to the interference and limitation of experimental conditions, some data are inaccurate or some data cannot be obtained, in order to obtain reliable, Based on the low rank matrix filling algorithm, a new low rank matrix filling algorithm with edge information is proposed. In this paper, the H3N2 influenza virus data from 1968-2003 were used to predict the antigenicity of influenza viruses by integrating the similarity information of HA protein sequences into the matrix filling model. Firstly, the low response data of hemagglutinin inhibition test were reestimated and the missing data were recovered. Compared with the existing methods, the RMS error of this algorithm is reduced by 37 times. Using these reestimated data to construct the antigen map and genetic map, the results show that the H3N2 influenza virus antigen evolution map is "S" type, genetic evolution map is semi-circular type. Further, this study analyzed the relationship between genetic evolution and antigen evolution of H3N2 influenza virus. It is found that the Spelman correlation coefficient between genetic distance and antigen distance is 0.83, which indicates that there is a high consistency between genetic evolution and antigen evolution, although there is a local difference between genetic evolution and antigen evolution. Based on the above algorithm, BMCSI, a method for selecting vaccine strains is proposed, and the selection of historical vaccine strains is evaluated. In addition, we applied the model to the sensitivity data of 491 cancer cell lines and 24 anticancer drugs in CCLE, and predicted the sensitivity of anticancer drugs by using the correlation between the rows and columns of the matrix and the characteristics of gene expression. The genes associated with drug sensitivity were then identified by using anti-cancer drug sensitivity data.
【學(xué)位授予單位】:浙江理工大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:O151.21;R373
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