病毒的属特异性蛋白质模式

eep Bansode
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In 2009, a novel swine-origin H1N1 strain of influenza A hastily unfold to over 213 countries in the first declared pandemic of the 21st century. And now, on August 8, 2014, the World Health Organization (WHO) Director-General Margaret Chan declared the Ebola outbreak in West Africa a “public fitness emergency of worldwide concern,” triggering powers below the 2005 International Health Regulations (IHR). The IHR require countries to increase national preparedness capacities, such as the obligation to file internationally huge events, habits surveillance, and exercising public fitness powers, while balancing human rights and global trade. 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引用次数: 1

摘要

在不断上升和重新出现的病毒感染的产生中,诊断及其相关领域在防治这些疾病方面发挥着主要作用。大量已公开的分子序列数据对改进新型诊断工具具有重要的实用价值。这种学习的先决条件之一是识别特征序列,即特定于特定家族/属/生物体的蛋白质/核苷酸序列的小片段。目前已有大量基于序列同源性/相似性的蛋白质特征序列归档资源。然而,这些资源没有考虑到在病毒诊断中具有广泛地位的分类学事实。目前的发现是一个努力明确地考虑到分类信息,从而得出属特异性的病毒蛋白的特征序列。从VirGen数据库接收到获取模式的初步事实,即多序列比对(MSA)。内部开发的perl脚本用于从MSA派生模式。然后通过对NCBI非冗余蛋白序列数据库的搜索来验证这些模式,从而能够计算它们的敏感性和特异性。这样的验证需要与真阳性和真阴性相关的数据集。真阳性数据集是从NCBI的分类学数据库中通过制定Entrez查询获得的,这样就可以检索到属于给定属的整个物种种类。真阴性数据集由属于不同于所讨论的属的任何蛋白质序列组成。在VirGen病毒19个科(RNA病毒)的262个蛋白中,有125个蛋白检测到模式,所有这些蛋白都是罕见的真阳性和假阳性序列。当将这些模式映射到相应的3D结构(25个独特的蛋白质数据库条目)时,这些模式被定位为能量网站和二聚化界面等重要有用区域的一部分。由此获得的独特的病毒特征序列/肽不仅在检测分析和治疗中有应用,而且可以作为病毒疫苗的假定靶点。病毒引发了人类历史上一些最严重和最致命的疾病大流行。天花是一种由天花病毒引起的传染性很强的人类疾病,在1980年被宣布根除之前,仅在20世纪就在全球范围内造成3亿至5亿人死亡。1918年至1919年的“西班牙流感”大流行感染了世界上大约三分之一的人口,估计造成5000万至1亿人死亡。在过去的半个世纪里,由动物源性新型病毒——马来西亚的尼帕病毒、澳大利亚的亨德拉病毒、美国的汉坦病毒、非洲的埃博拉病毒,以及艾滋病毒(人类免疫缺陷病毒)、各种流感亚型、SARS(严重急性呼吸综合征)和MERS(中东呼吸综合征)冠状病毒——引发的致命疾病爆发,突显了掌握影响病毒性疾病出现和传播因素的紧迫性。自1981年发现第一例病例以来,世界上现代主要的传染病杀手艾滋病毒已导致约3600万人死亡。2012年,有200多万人新感染艾滋病毒,160万人死于艾滋病毒/艾滋病。2009年,一种新型猪源型H1N1甲型流感病毒迅速传播到213多个国家,成为21世纪首次宣布的大流行。现在,2014年8月8日,世界卫生组织(WHO)总干事陈冯富珍宣布西非爆发的埃博拉疫情是“全球关注的公共卫生紧急事件”,触发了2005年《国际卫生条例》(IHR)之下的权力。《国际卫生条例》要求各国在平衡人权和全球贸易的同时,提高国家防范能力,例如对国际重大事件进行申报的义务、习惯监测和行使公共健身权力。扩展的抽象
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Genus specific protein patterns of viruses
In the generation of rising and re-emerging viral infections, diagnostics and its allied fields have a predominant function to play in combating the diseases. Enormous quantity of the molecular sequence data handy in the public domain has the practicable to contribute in a important way in the improvement of novel diagnostic tools. One of the perquisites for such a learn about is the identification of signature sequences i.e., small stretches of protein/nucleotide sequences that are special to a given family/genus/organism. There exist numerous resources in the public area archiving signature sequences of proteins based on sequence identity/ similarity. However, these resources do not take into account the taxonomic facts which has a extensive position to play in viral diagnostics. The present find out about is an effort to explicitly take into account the taxonomic information and thereby derive genus-specific signature sequences of viral proteins. The preliminary facts for obtaining patterns viz., multiple sequence alignment (MSA) is received from VirGen database. An in-house developed perl script is used to derive the patterns from the MSA. The patterns are then validated by using search against the non-redundant protein sequence database at NCBI, thereby enabling the computation of their sensitivity and specificity. Such a validation requires datasets pertaining to true-positives and true-negatives. True-positive dataset is acquired from the taxonomy database at NCBI by formulating an Entrez query such that the whole variety of species belonging to a given genus is retrieved. The true-negative dataset constituted of any protein sequence that belongs to genus different than the one in question. Of the 262 proteins belonging to 19 families (RNA viruses) in VirGen, patterns should be detected for 125 proteins, all of which actually uncommon truepositives and false-positive sequences. These patterns when mapped onto their corresponding 3D constructions (25 unique entries of Protein Data Bank) are located to be part of essential useful regions like energetic website and dimerization interface. The unique viral signature sequences/peptides consequently obtained have applications not only in detection assays and as therapeutics but also can serve as putative targets for viral vaccines. Viruses have induced some of the most dramatic and deadly sickness pandemics in human history. Before it was declared to be eradicated in 1980, smallpox, a rather contagious human disorder caused by means of the Variola virus, killed 300 to five hundred million humans international in the 20th century alone. The 1918–1919 “Spanish flu” pandemic infected roughly one-third of the world's human populace and brought on an estimated 50 to a hundred million deaths. In the past half century, deadly disorder outbreaks brought about through novel viruses of animal origin—Nipah virus in Malaysia, Hendra virus in Australia, hantavirus in the United States, Ebola virus in Africa, along with HIV (human immunodeficiency virus), various influenza subtypes, and the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses—have underscored the urgency of grasp elements influencing viral disease emergence and spread. The world's modern main infectious killer, HIV, has prompted an estimated 36 million deaths since the first cases were pronounced in 1981. In 2012, more than two million people were newly contaminated with the virus, and 1.6 million died of HIV/AIDS. In 2009, a novel swine-origin H1N1 strain of influenza A hastily unfold to over 213 countries in the first declared pandemic of the 21st century. And now, on August 8, 2014, the World Health Organization (WHO) Director-General Margaret Chan declared the Ebola outbreak in West Africa a “public fitness emergency of worldwide concern,” triggering powers below the 2005 International Health Regulations (IHR). The IHR require countries to increase national preparedness capacities, such as the obligation to file internationally huge events, habits surveillance, and exercising public fitness powers, while balancing human rights and global trade. Extended Abstract
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