新型冠状病毒(SARS-CoV-2)蛋白靶位的生信分析

目前新型冠状病毒肺炎(COVID-19)疫情仍在全球肆虐,但尚无针对该病毒的治疗特效药.在此背景,以美国化学文摘社(Chemical Abstracts Service,CAS)提供的SARS-CoV-2病毒及宿主蛋白靶标为研究对象,运用基因功能富集、蛋白网络等方法进行生物信息分析.结果发现,人网格蛋白介导型内吞和依赖...     

蛋白质功能预测方法概述

蛋白质是生物体内最必需也是最通用的大分子,对它们功能的认识对于科学领域和农业领域的发展有着至关重要的作用。随着后基因组时代的发展,NCBI数据库中迅速涌现出大量不明结构与功能的蛋白质序列,这些蛋白质序列甚至一跃成了研究的热点。近几十年来蛋白质功能预测的方法不断被完善。由最初的仅基于蛋白质序列或3D结构信息的方法衍生出更多的基于序列相似性、基于结构基序、基于相互作用网络等新方法,这些新型方法采用新的算法、新的研究思路和技术手段,力求得到准确性与普遍性并存,能够被广泛应用的蛋白质功能预测方法。本文综述了近年来蛋白质功能预测的方法,并将这些研究方法分类归纳,各自阐明了每类方法的优缺点。     

枯草芽孢杆菌同义密码子使用偏性对蛋白质折叠速率的影响

目前,有关同义密码子使用偏性对蛋白质折叠的影响研究中,样本蛋白均来源于不同的物种。考虑到同义密码子使用偏性的物种差异性,选取枯草杆菌的核蛋白为研究对象。首先,将每条核蛋白按二级结构截取为α螺旋片段、β折叠片段和无规卷曲（α-β混合）片段,并计算其蛋白质折叠速率。然后,整理每个片段相应的核酸序列信息,计算其同义密码子使用度。在此基础上,分析枯草芽孢杆菌核蛋白的同义密码子使用偏性与蛋白质折叠速率的相关性。发现对于不同二级结构的肽链片段,都有部分密码子的使用偏性与其对应的肽链折叠速率显著相关。进一步分析发现,与肽链片段折叠速率显著相关的密码子绝大部分为枯草杆菌全序列或核蛋白序列的每一组同义密码子中使用度最高的密码子。结果表明,在蛋白质的折叠过程中,枯草芽孢杆菌的同义密码子使用偏性起着重要作用。     

基于设计模板的BRD-like折叠类型综合分类方法

蛋白质折叠规律研究是生命科学重大前沿课题,折叠类型分类是蛋白质折叠研究的基础。构建BRD-like折叠类型模板数据库,建立了基于多模板的综合分类方法,并用于该折叠类型的分类。对实验集的12 117个样本进行检验,结果的敏感性、特异性分别为0.923和0.997,MCC值为0.72;对独立检验集2 260个样本的检验,结果发现:敏感性、特异性分别为0.941和0.998,MCC值为0.86.结果表明:基于多模板的综合分类方法可用于蛋白质折叠类型分类。     

基于HP模型的蛋白质折叠问题的研究

基于蛋白质二维HP模型提出改进的遗传算法对真实蛋白质进行计算机折叠模拟。结果显示疏水能量函数最小值的蛋白质构象对应含疏水核心的稳定结构,疏水作用在蛋白质折叠中起主要作用。研究表明二维HP模型在蛋白质折叠研究中是可行的和有效的并为进一步揭示蛋白质折叠机理提供重要参考信息。     

基于CNN与LSTM模型的蛋白质二级结构预测

蛋白质结构的预测在理解蛋白质结构组成和蛋白质的生物学功能有重要意义,而蛋白质二级结构预测是蛋白质结构预测的重要环节。当PSSM位置特异性进化矩阵被广泛应用于将蛋白质初级结构序列编码作为输入样本后,每个残基可以被表示成二维空间的数据平面,由此文中尝试利用卷积神经网络对其进行训练。文中还设计了另一种卷积神经网络,利用长短记忆网络感知了CNN最后卷积特征面的横向特征和纵向特征后连同卷积神经网络的全连接共同完成分类,最后用ensemble方法对两类卷积神经网络模型进行了整合,最终ensemble方法中包含两类卷积神经网络的六个模型,在CB513蛋白质数据集测得的Q3结果为77.2。     

Enhancing Bioinformatics and Genomics Courses: Building Capacity and Skills via Lab Meeting Activities

Reading, writing, publishing, and publicly presenting scientific works are vital for a young researcher's profile building and career development. Generally, the traditional educational curricula do not offer training possibilities to learn and practice how to prepare, write, and present scientific works. These are rather a part of lab meeting activities in research groups. The lack of such training is more critical in some developing countries because this adds to the rare opportunities to discuss and become involved in the exchanges on state of the art scientific literature. Here the authors relate their experience in introducing a weekly 1-day lab meeting in the framework of two previously organized 3-month courses on “Bioinformatics and Genome Analyses”. The main activities which are developed during these lab meetings include scientific literature follow up as well as preparing and presenting oral and written scientific reviews. These activities prove to be useful for a student's self-confidence building, for enhancing their active participation during the lectures and practical sessions, as well as for the positive impact on running the whole course program. Incorporation of such lab meeting activities in the course program significantly improves the capacity building of the participants, their analytical and critical reading of scientific literature, as well as communication skills. In this work it is shown how to proceed with the different steps involved in the implementation of lab meeting activities, and to recommend their regular institution in similar courses.     

Mobility measurements of immunomagnetically labeled cells allow quantitation of secondary antibody binding amplification.

Magnetic cell separation methods commonly utilize paramagnetic materials conjugated to antibodies that target specific cell surface molecules. The amount of magnetic material bound to a cell is directly proportional to the magnetophoretic mobility of that cell. A mathematical model has been developed which characterizes the fundamental parameters controlling the amount of magnetic material bound, and thus, the magnetophoretic mobility of an immunomagnetically labeled cell. In characterization of the paramagnetic labeling, one of the parameters of interest is the increase in magnetophoretic mobility due to the secondary antibody binding to multiple epitopes on the primary antibody, referred to as the "secondary antibody binding amplification," Psi. Secondary antibody-binding amplification has been investigated and quantitated by comparing the mobilities of lymphocytes directly labeled with anti-CD4 MACS (Miltenyi Biotec, Auburn, CA) magnetic nanoparticle antibody with the mobilities of lymphocytes from the same sample labeled with two different indirect antibody-labeling schemes. Each indirect labeling scheme incorporated a primary mouse anti-CD4 FITC antibody that provides both FITC and mouse-specific binding sites for two different secondary antibody-magnetic nanoparticle conjugates: either anti-FITC MACS magnetic nanoparticle antibody or anti-mouse MACS magnetic nanoparticle antibody. The magnetophoretic mobilities of the immunomagnetically labeled cells were obtained using Cell Tracking Velocimetry (CTV). The results indicate that an average of 3.4 anti-FITC MACS magnetic nanoparticle antibodies bind to each primary CD4 FITC antibody, Psi(1,2f) = 3.4 +/- 0.33, and that approximately one, Psi(1,2m) = 0.98 +/- 0.081, anti-mouse MACS magnetic nanoparticle antibody binds to each primary mouse CD4 FITC antibody on a CD4 positive lymphocyte. These results have provided a better understanding of the antibody-binding mechanisms used in paramagnetic cell labeling for magnetic cell separation.     

Lipid-induced Pore Formation of the Bacillus thuringiensis Cry1Aa Insecticidal Toxin

After activation, Bacillus thuringiensis (Bt) insecticidal toxin forms pores in larval midgut epithelial cell membranes, leading to host death. Although the crystal structure of the soluble form of Cry1Aa has been determined, the conformation of the pores and the mechanism of toxin interaction with and insertion into membranes are still not clear. Here we show that Cry1Aa spontaneously inserts into lipid mono- and bilayer membranes of appropriate compositions. Fourier Transform InfraRed spectroscopy (FTIR) indicates that insertion is accompanied by conformational changes characterized mainly by an unfolding of the β-sheet domains. Moreover, Atomic Force Microscopy (AFM) imaging strongly suggests that the pores are composed of four subunits surrounding a 1.5 nm diameter central depression. Received: 14 July 2000/Revised: 28 December 2000