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  本文關(guān)鍵詞： PRRSV ORF5 結(jié)構(gòu)比較 疫苗　出處：《吉林大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：RNA作為一種生物大分子在多種生命活動過程中起著至關(guān)重要的作用。RNA的功能與其結(jié)構(gòu)密切相關(guān),結(jié)構(gòu)決定了功能的變化。而RNA二級結(jié)構(gòu)是RNA結(jié)構(gòu)中最核心部分,是RNA一級結(jié)構(gòu)與RNA三級結(jié)構(gòu)間溝通的橋梁,最具保守性。因此,RNA二級結(jié)構(gòu)的研究成為重要的研究方向,其結(jié)構(gòu)比較也日益成為研究的焦點(diǎn)。豬繁殖與呼吸綜合征(PRRS)會導(dǎo)致母豬和幼豬的死亡,傳播速度快,死亡率高,對養(yǎng)豬業(yè)造成巨大危害。目前針對該病沒有有效藥物進(jìn)行治療,僅能采用注射疫苗的方式進(jìn)行防治,但由于PRRSV具有高度變異性,導(dǎo)致疫苗在免疫效力、安全性等方面仍無法滿足實(shí)際需求,在實(shí)際使用中難以推廣,因此研發(fā)可靠、高效的新一代疫苗顯得尤為迫切。尋找結(jié)構(gòu)穩(wěn)定的核心免疫RNA序列是設(shè)計PRRVS疫苗的關(guān)鍵。采用生物信息學(xué)手段對PRRSV的RNA進(jìn)行分析,確定可能的、關(guān)鍵的、穩(wěn)定的RNA序列,為疫苗的制備提供理論基礎(chǔ),是本文的研究內(nèi)容。本文把計算機(jī)科學(xué)與生物信息學(xué)結(jié)合在一起,構(gòu)建了一種基于結(jié)構(gòu)的序列比較分析模型,并將其應(yīng)用到PRRSV的分析中。模型整體流程如下所述:首先基于特征的RNA數(shù)據(jù)篩選,構(gòu)建多特征篩選模型,提高數(shù)據(jù)有效性,提高處理效率,減少資源利用率�；谝延涗浀腜RRSV的RNA數(shù)據(jù),分別將生源地、毒性強(qiáng)弱以及ORF5開放閱讀框等做為篩選特征,進(jìn)行多次特征篩選得到目標(biāo)數(shù)據(jù)集。其次采用結(jié)構(gòu)比較方法對目標(biāo)數(shù)據(jù)集進(jìn)行比較。由于一級結(jié)構(gòu)具有較高的重復(fù),因此結(jié)構(gòu)比較分析的結(jié)果更多依賴于二級結(jié)構(gòu)比較,因?yàn)镽NA二級結(jié)構(gòu)相對于一級結(jié)構(gòu)而言更加保守,更能對生物分子的功能起決定性作用。最后根據(jù)比較的結(jié)果得出了與其對應(yīng)的結(jié)論,設(shè)計出相應(yīng)的新型疫苗。本文的技術(shù)創(chuàng)新與主要的工作集中在數(shù)據(jù)篩選以及RNA二級結(jié)構(gòu)比較這兩方面。1、在數(shù)據(jù)篩選方面。本文選取序列長度在15000nt的初級序列;選取生源地、毒性強(qiáng)弱以及來源和有機(jī)體的不同作為第一次篩選的特征;由于ORF5序列在PRRSV分離株間存在高度變異性,是保守性最差的開放閱讀框,選取此處數(shù)據(jù)為后續(xù)的數(shù)據(jù)處理工作提供了極大的便利,省去了許多資源浪費(fèi),因此選取ORF5開放閱讀框作為第二次篩選的特征。2、建立RNA二級結(jié)構(gòu)比較方法。本文基于樹結(jié)構(gòu)與向量的對應(yīng)關(guān)系,抽象出了一種結(jié)構(gòu)中點(diǎn)括號表示法同與其對應(yīng)的向量表示方法間轉(zhuǎn)換方式;設(shè)計了一種基于動態(tài)規(guī)劃思想的改進(jìn)的樹結(jié)構(gòu)的比較算法,利用向量的差異程度來查找其最大的相同子結(jié)構(gòu)。本文對PRRSV分離株的RNA進(jìn)行比較分析,由分析結(jié)果可知雖然一級結(jié)構(gòu)相似度均在50%以上但有較高重復(fù),無法提供理論支持。然而二級結(jié)構(gòu)無重復(fù)且相似性均在0.5%以下,相似性仍然較低,但存在相似性相近的地方,表明存在部分相似結(jié)構(gòu)但不是很完整,提取出這些結(jié)構(gòu)可用于疫苗的設(shè)計中。
[Abstract]:As a biological macromolecule, RNA plays an important role in many life processes. The function of RNA is closely related to its structure. The RNA secondary structure is the core part of the RNA structure and the bridge between the RNA primary structure and the RNA tertiary structure, which is the most conservative. The study of RNA secondary structure has become an important research direction, and its structure comparison has increasingly become the focus of research. Porcine reproductive and respiratory syndrome (PRRSs) will lead to the death of sows and young pigs, and the transmission speed is fast. At present, there is no effective drug to treat the disease, only can be treated by injection vaccine, but because of the high variability of PRRSV. As a result, the vaccine can not meet the actual needs in immunization efficacy, safety and other aspects, so it is difficult to promote in practical use, so research and development is reliable. Efficient new generation vaccine is particularly urgent. The key to design PRRVS vaccine is to find a stable core immune RNA sequence. Bioinformatics is used to analyze the RNA of PRRSV. The identification of possible, critical and stable RNA sequences, which provide a theoretical basis for vaccine preparation, is the subject of this paper. This paper combines computer science with bioinformatics. This paper constructs a structure-based sequence comparison analysis model and applies it to the analysis of PRRSV. The overall process of the model is as follows: firstly, RNA data filtering based on features. Build multi-feature screening model to improve data efficiency, improve processing efficiency, reduce resource utilization. Based on recorded PRRSV RNA data, respectively. Toxicity and ORF5 open reading box were used as screening characteristics. The target data set is obtained by multiple feature filtering. Secondly, the target data set is compared by the structure comparison method. Because of the high repetition of the primary structure. Therefore, the results of the structural comparison analysis are more dependent on the secondary structure comparison, because the secondary structure of RNA is more conservative than the primary structure. It can play a more decisive role in the function of biomolecules. Finally, according to the results of comparison, the corresponding conclusions are obtained. The technological innovation and main work of this paper focus on data screening and RNA secondary structure comparison. 1. In the aspect of data filtering, we select the primary sequence with the length of 15000nt; The characteristics of the first screening were selected, such as the source, the toxicity, the source and the organism. Because of the high variability of ORF5 sequence among PRRSV isolates, it is the most conservative open reading box, so it is very convenient to select the data here for the subsequent data processing. A lot of waste of resources is saved, so ORF5 open reading box is selected as the feature of the second filter. The comparison method of RNA secondary structure is established. This paper based on the corresponding relationship between tree structure and vector. A transformation method between the midpoint parenthesis representation and the corresponding vector representation is presented. An improved tree structure comparison algorithm based on the idea of dynamic programming is designed to find the largest identical substructure by using the difference degree of vector. The RNA of PRRSV isolate is compared and analyzed in this paper. The results show that although the primary structure similarity is more than 50%, but has high repetition, it can not provide theoretical support. However, the secondary structure has no repetition and the similarity is below 0.5%, and the similarity is still low. But there are some similarities which indicate that there are some similar structures but not very complete. These structures can be used in vaccine design.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：S852.4

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