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Super-rapid race for saving lives by developing COVID-19 vaccines. 通过开发COVID-19疫苗来拯救生命的超高速竞赛。
IF 1.9 Q1 Medicine Pub Date : 2021-03-25 DOI: 10.1515/jib-2021-0002
Anusha Uttarilli, Sridhar Amalakanti, Phaneeswara-Rao Kommoju, Srihari Sharma, Pankaj Goyal, Gowrang Kasaba Manjunath, Vineet Upadhayay, Alisha Parveen, Ravi Tandon, Kumar Suranjit Prasad, Tikam Chand Dakal, Izhar Ben Shlomo, Malik Yousef, Muniasamy Neerathilingam, Abhishek Kumar

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people and claimed thousands of lives. Starting in China, it is arguably the most precipitous global health calamity of modern times. The entire world has rocked back to fight against the disease and the COVID-19 vaccine is the prime weapon. Even though the conventional vaccine development pipeline usually takes more than a decade, the escalating daily death rates due to COVID-19 infections have resulted in the development of fast-track strategies to bring in the vaccine under a year's time. Governments, companies, and universities have networked to pool resources and have come up with a number of vaccine candidates. Also, international consortia have emerged to address the distribution of successful candidates. Herein, we summarize these unprecedented developments in vaccine science and discuss the types of COVID-19 vaccines, their developmental strategies, and their roles as well as their limitations.

由严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2)引起的2019年冠状病毒病(COVID-19)大流行已经影响了数百万人,夺去了数千人的生命。从中国开始,可以说是现代最危险的全球卫生灾难。整个世界都在与这种疾病作斗争,COVID-19疫苗是主要武器。尽管传统的疫苗开发管道通常需要十多年的时间,但由于COVID-19感染导致的每日死亡率不断上升,因此需要制定快速通道战略,以便在一年的时间内开发出疫苗。政府、公司和大学已经联网,汇集资源,并提出了一些候选疫苗。此外,已经出现了国际财团来解决成功候选人的分配问题。在此,我们总结了这些前所未有的疫苗科学进展,并讨论了COVID-19疫苗的类型、开发策略、作用和局限性。
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引用次数: 13
Special issue on COVID-19 data integration opportunities and vaccine development strategies. 关于COVID-19数据整合机会和疫苗开发战略的特刊。
IF 1.9 Q1 Medicine Pub Date : 2021-03-22 DOI: 10.1515/jib-2021-0006
Jens Allmer
Viral infections affect a large part of the human population once or several times each year. Coronaviruses (CoV) are part of the viruses which cause ailments such as the common cold. With SARS-CoV-1, a dangerous variant of CoV caused an epidemic that did not spread worldwide (2002–2004). It has been contained with less than one thousand fatalities (WHO). Another beta coronavirus causing the middle east respiratory syndrome (MERS) broke out about a decade later (2013). While MERS cases are still present in 2021 (most cases reported by Saudi Arabia), the cumulative death toll is below one thousand despite a high case-to-fatality ratio of around 30% [1]. In 2019 SARS-CoV-2 caused a pandemic with abundant worldwide infections and about two million fatalities in early 2021 (http://covid19.who.int). With the SARS-CoV-2 pandemic active for more than one year, vaccines with emergency admittance are being delivered. Interestingly, during 50 years of research on vaccines against coronaviridae, such approaches are only now becoming available (Figure 1). Vaccination of a sufficiently large cohort of individuals to control the pandemic will take long at current vaccination rates. Therefore, it is essential to continue studying SARS-CoV-2 and try additional routes to prevent the virus’s spread or the disease. Yousef et al. state that testing data is fragmented and not readily available [2]. With a relatively large dataset provided by the Israeli government, they trained a machine-learning algorithm that aided in ranking symptoms, allowing testing prioritization. Demirci and Sacar Demirci show how post-transcriptional gene regulation can be involved in the COVID-19 disease and investigate different miRNAs’ targets and their differential expression [3]. Gültekin and Allmer show how novel information such as RNA binding potential and predicted CoV microRNAs could be incorporated into genome browsers [4]. Such data can help RNA-based drug design. Ahsan et al. tie together many resources with CoV’ information ranging from genomic data to clinical trials [5]. Due to the amount of data generated in the last year, such a resource was desperately needed. OverCOVID will help researchers to find the information they need and may enable integrative studies. Finally, Uttarilli et al. discuss the rapid development of COVID-19 vaccines [6]. Thus, this special issue brings together two applications of COVID-19 data, one visualization of such data, a resource potentially delivering data with integration potential, and a review of vaccine development, which could benefit from the resources mentioned above.
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引用次数: 2
OverCOVID: an integrative web portal for SARS-CoV-2 bioinformatics resources. OverCOVID: SARS-CoV-2生物信息学资源综合门户网站。
IF 1.9 Q1 Medicine Pub Date : 2021-03-19 DOI: 10.1515/jib-2020-0046
Md Asif Ahsan, Yongjing Liu, Cong Feng, Ralf Hofestädt, Ming Chen

Outbreaks of COVID-19 caused by the novel coronavirus SARS-CoV-2 is still a threat to global human health. In order to understand the biology of SARS-CoV-2 and developing drug against COVID-19, a vast amount of genomic, proteomic, interatomic, and clinical data is being generated, and the bioinformatics researchers produced databases, webservers and tools to gather those publicly available data and provide an opportunity of analyzing such data. However, these bioinformatics resources are scattered and researchers need to find them from different resources discretely. To facilitate researchers in finding the resources in one frame, we have developed an integrated web portal called OverCOVID (http://bis.zju.edu.cn/overcovid/). The publicly available webservers, databases and tools associated with SARS-CoV-2 have been incorporated in the resource page. In addition, a network view of the resources is provided to display the scope of the research. Other information like SARS-CoV-2 strains is visualized and various layers of interaction resources is listed in distinct pages of the web portal. As an integrative web portal, the OverCOVID will help the scientist to search the resources and accelerate the clinical research of SARS-CoV-2.

由新型冠状病毒SARS-CoV-2引起的2019冠状病毒病(COVID-19)疫情仍对全球人类健康构成威胁。为了了解SARS-CoV-2的生物学特性并开发针对COVID-19的药物,大量的基因组学、蛋白质组学、原子间学和临床数据正在产生,生物信息学研究人员开发了数据库、网络服务器和工具来收集这些公开可用的数据,并提供分析这些数据的机会。然而,这些生物信息学资源是分散的,研究人员需要从不同的资源中离散地找到它们。为了方便研究人员在一个框架内查找资源,我们开发了一个名为OverCOVID的综合门户网站(http://bis.zju.edu.cn/overcovid/)。与SARS-CoV-2相关的公开网络服务器、数据库和工具已纳入资源页面。此外,还提供了资源的网络视图,以显示研究的范围。其他信息,如SARS-CoV-2菌株,是可视化的,各种层次的互动资源在门户网站的不同页面上列出。作为一个综合性门户网站,OverCOVID将帮助科学家搜索资源,加快SARS-CoV-2的临床研究。
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引用次数: 9
Circular RNA-MicroRNA-MRNA interaction predictions in SARS-CoV-2 infection. 环状RNA-MicroRNA-MRNA相互作用预测SARS-CoV-2感染。
IF 1.9 Q1 Medicine Pub Date : 2021-03-17 DOI: 10.1515/jib-2020-0047
Yılmaz Mehmet Demirci, Müşerref Duygu Saçar Demirci

Different types of noncoding RNAs like microRNAs (miRNAs) and circular RNAs (circRNAs) have been shown to take part in various cellular processes including post-transcriptional gene regulation during infection. MiRNAs are expressed by more than 200 organisms ranging from viruses to higher eukaryotes. Since miRNAs seem to be involved in host-pathogen interactions, many studies attempted to identify whether human miRNAs could target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNAs as an antiviral defence mechanism. In this work, a machine learning based miRNA analysis workflow was developed to predict differential expression patterns of human miRNAs during SARS-CoV-2 infection. In order to obtain the graphical representation of miRNA hairpins, 36 features were defined based on the secondary structures. Moreover, potential targeting interactions between human circRNAs and miRNAs as well as human miRNAs and viral mRNAs were investigated.

不同类型的非编码rna,如microRNAs (miRNAs)和环状rna (circRNAs),已被证明在感染期间参与各种细胞过程,包括转录后基因调控。从病毒到高等真核生物,有200多种生物表达mirna。由于miRNAs似乎参与了宿主-病原体的相互作用,许多研究试图确定人类miRNAs是否可以靶向严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) mrna作为抗病毒防御机制。在这项工作中,开发了一种基于机器学习的miRNA分析工作流程,以预测SARS-CoV-2感染期间人类miRNA的差异表达模式。为了获得miRNA发夹的图形化表示,我们根据二级结构定义了36个特征。此外,还研究了人类circRNAs与miRNAs以及人类miRNAs与病毒mrna之间潜在的靶向相互作用。
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引用次数: 17
Novel perspectives for SARS-CoV-2 genome browsing. SARS-CoV-2基因组浏览的新视角
IF 1.9 Q1 Medicine Pub Date : 2021-03-16 DOI: 10.1515/jib-2021-0001
Visam Gültekin, Jens Allmer

SARS-CoV-2 has spread worldwide and caused social, economic, and health turmoil. The first genome assembly of SARS-CoV-2 was produced in Wuhan, and it is widely used as a reference. Subsequently, more than a hundred additional SARS-CoV-2 genomes have been sequenced. While the genomes appear to be mostly identical, there are variations. Therefore, an alignment of all available genomes and the derived consensus sequence could be used as a reference, better serving the science community. Variations are significant, but representing them in a genome browser can become, especially if their sequences are largely identical. Here we summarize the variation in one track. Other information not currently found in genome browsers for SARS-CoV-2, such as predicted miRNAs and predicted TRS as well as secondary structure information, were also added as tracks to the consensus genome. We believe that a genome browser based on the consensus sequence is better suited when considering worldwide effects and can become a valuable resource in the combating of COVID-19. The genome browser is available at http://cov.iaba.online.

SARS-CoV-2已在全球传播,并造成社会、经济和卫生动荡。首个SARS-CoV-2基因组组装体是在武汉产生的,具有广泛的参考价值。随后,又对100多个SARS-CoV-2基因组进行了测序。虽然基因组看起来基本相同,但也存在差异。因此,所有可用的基因组比对和衍生的共识序列可以作为参考,更好地服务于科学界。变异是很重要的,但在基因组浏览器中表示它们可能会变得很困难,特别是如果它们的序列在很大程度上是相同的。在这里,我们总结一个轨道的变化。目前在SARS-CoV-2基因组浏览器中未发现的其他信息,如预测的mirna和预测的TRS以及二级结构信息,也被添加到共识基因组中。我们认为,基于共识序列的基因组浏览器更适合考虑全球影响,可以成为抗击COVID-19的宝贵资源。基因组浏览器可在http://cov.iaba.online上获得。
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引用次数: 2
Clinical presentation of COVID-19 - a model derived by a machine learning algorithm. COVID-19 的临床表现--通过机器学习算法得出的模型。
IF 1.9 Q1 Medicine Pub Date : 2021-03-04 DOI: 10.1515/jib-2020-0050
Malik Yousef, Louise C Showe, Izhar Ben Shlomo

COVID-19 pandemic has flooded all triage stations, making it difficult to carefully select those most likely infected. Data on total patients tested, infected, and hospitalized is fragmentary making it difficult to easily select those most likely to be infected. The Israeli Ministry of Health made public its registry of immediate clinical data and the respective status of infected/not infected for all viral DNA tests performed up to Apr. 18th, 2020 including almost 120,000 tests. We used a machine-learning algorithm to find out which immediate clinical elements mattered the most in identifying the true status of the tested persons including age or gender matter, to enable future better allocation of surveillance policy for those belonging to high-risk groups. In addition to the analyses applied on the first batch of the available data (Apr. 11th), we further tested the algorithm on the independent second batch (Apr. 12th to 18th). Fever, cough and headache were the most diagnostic, differing in degree of importance in different subgroups. Higher percentage of men were found positive (9.3 vs. 7.3%), but gender did not matter for the clinical presentation. The prediction power of the model was high, with accuracy of 0.84 and area under the curve 0.92. We provide a hand-held short checklist with verbal description of importance for the leading symptoms, which should expedite the triage and enable proper selection of people for further follow-up.

COVID-19 大流行充斥着所有分流站,很难仔细挑选出最有可能被感染的患者。关于接受检测、受感染和住院患者总数的数据非常零散,因此很难轻松选出最有可能受感染的患者。以色列卫生部公布了截至 2020 年 4 月 18 日进行的所有病毒 DNA 检测的即时临床数据和感染/未感染状态登记,其中包括近 12 万次检测。我们使用了一种机器学习算法,以找出哪些即时临床要素(包括年龄或性别要素)对确定受检者的真实状况最为重要,从而在未来更好地分配针对高危人群的监测政策。除了对第一批可用数据(4 月 11 日)进行分析外,我们还对独立的第二批数据(4 月 12 日至 18 日)进行了进一步测试。发热、咳嗽和头痛是最具诊断意义的症状,在不同的亚群中其重要程度不同。男性阳性比例较高(9.3% 对 7.3%),但性别与临床表现无关。该模型的预测能力很强,准确率为 0.84,曲线下面积为 0.92。我们提供了一份手持式简短核对表,并对主要症状的重要性进行了口头描述,该核对表应能加快分诊速度,并能正确选择需要进一步随访的人群。
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引用次数: 0
BioDWH2: an automated graph-based data warehouse and mapping tool. BioDWH2:一个自动化的基于图形的数据仓库和映射工具。
IF 1.9 Q1 Medicine Pub Date : 2021-02-22 DOI: 10.1515/jib-2020-0033
Marcel Friedrichs

Data integration plays a vital role in scientific research. In biomedical research, the OMICS fields have shown the need for larger datasets, like proteomics, pharmacogenomics, and newer fields like foodomics. As research projects require multiple data sources, mapping between these sources becomes necessary. Utilized workflow systems and integration tools therefore need to process large amounts of heterogeneous data formats, check for data source updates, and find suitable mapping methods to cross-reference entities from different databases. This article presents BioDWH2, an open-source, graph-based data warehouse and mapping tool, capable of helping researchers with these issues. A workspace centered approach allows project-specific data source selections and Neo4j or GraphQL server tools enable quick access to the database for analysis. The BioDWH2 tools are available to the scientific community at https://github.com/BioDWH2.

数据集成在科学研究中发挥着至关重要的作用。在生物医学研究中,OMICS领域已经表明需要更大的数据集,如蛋白质组学、药物基因组学和食品组学等新领域。由于研究项目需要多个数据源,因此有必要在这些数据源之间进行映射。因此,使用的工作流系统和集成工具需要处理大量异构数据格式,检查数据源更新,并找到合适的映射方法来交叉引用不同数据库中的实体。本文介绍了BioDWH2,一个开源的、基于图形的数据仓库和映射工具,能够帮助研究人员解决这些问题。以工作空间为中心的方法允许选择特定于项目的数据源,Neo4j或GraphQL服务器工具允许快速访问数据库进行分析。BioDWH2工具可在https://github.com/BioDWH2.
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引用次数: 4
A computational model for GPCR-ligand interaction prediction. 用于预测 GPCR 与配体相互作用的计算模型。
IF 1.5 Q3 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2020-12-29 DOI: 10.1515/jib-2019-0084
Shiva Karimi, Maryam Ahmadi, Farjam Goudarzi, Reza Ferdousi

G protein-coupled receptors (GPCRs) play an essential role in critical human activities, and they are considered targets for a wide range of drugs. Accordingly, based on these crucial roles, GPCRs are mainly considered and focused on pharmaceutical research. Hence, there are a lot of investigations on GPCRs. Experimental laboratory research is very costly in terms of time and expenses, and accordingly, there is a marked tendency to use computational methods as an alternative method. In this study, a prediction model based on machine learning (ML) approaches was developed to predict GPCRs and ligand interactions. Decision tree (DT), random forest (RF), multilayer perceptron (MLP), support vector machine (SVM), and Naive Bayes (NB) were the algorithms that were investigated in this study. After several optimization steps, receiver operating characteristic (ROC) for DT, RF, MLP, SVM, and NB algorithm were 95.2, 98.1, 96.3, 95.5, and 97.3, respectively. Accordingly final model was made base on the RF algorithm. The current computational study compared with others focused on specific and important types of proteins (GPCR) interaction and employed/examined different types of sequence-based features to obtain more accurate results. Drug science researchers could widely use the developed prediction model in this study. The developed predictor was applied over 16,132 GPCR-ligand pairs and about 6778 potential interactions predicted.

G 蛋白偶联受体(GPCR)在人类的重要活动中发挥着至关重要的作用,被认为是多种药物的靶点。因此,基于这些关键作用,GPCR 主要被视为药物研究的重点。因此,有关 GPCR 的研究层出不穷。实验室实验研究在时间和费用上都非常昂贵,因此,人们明显倾向于使用计算方法作为替代方法。本研究开发了一种基于机器学习(ML)方法的预测模型,用于预测 GPCR 与配体的相互作用。本研究研究了决策树(DT)、随机森林(RF)、多层感知器(MLP)、支持向量机(SVM)和奈夫贝叶斯(NB)等算法。经过多个优化步骤后,DT、RF、MLP、SVM 和 NB 算法的接收操作特征(ROC)分别为 95.2、98.1、96.3、95.5 和 97.3。因此,最终模型是基于 RF 算法建立的。目前的计算研究与其他研究相比,侧重于特定和重要类型的蛋白质(GPCR)相互作用,并采用/研究了不同类型的基于序列的特征,以获得更准确的结果。药物科学研究人员可以广泛使用本研究开发的预测模型。所开发的预测模型应用于 16 132 对 GPCR 配体,预测出了约 6778 种潜在的相互作用。
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引用次数: 0
A novel gene expression test method of minimizing breast cancer risk in reduced cost and time by improving SVM-RFE gene selection method combined with LASSO. 一种改进SVM-RFE基因选择方法并结合LASSO的新型基因表达检测方法,在降低成本和时间内降低乳腺癌风险。
IF 1.9 Q1 Medicine Pub Date : 2020-12-29 DOI: 10.1515/jib-2019-0110
Madhuri Gupta, Bharat Gupta

Breast cancer is the leading diseases of death in women. It induces by a genetic mutation in breast cancer cells. Genetic testing has become popular to detect the mutation in genes but test cost is relatively expensive for several patients in developing countries like India. Genetic test takes between 2 and 4 weeks to decide the cancer. The time duration suffers the prognosis of genes because some patients have high rate of cancerous cell growth. In the research work, a cost and time efficient method is proposed to predict the gene expression level on the basis of clinical outcomes of the patient by using machine learning techniques. An improved SVM-RFE_MI gene selection technique is proposed to find the most significant genes related to breast cancer afterward explained variance statistical analysis is applied to extract the genes contain high variance. Least Absolute Shrinkage Selector Operator (LASSO) and Ridge regression techniques are used to predict the gene expression level. The proposed method predicts the expression of significant genes with reduced Root Mean Square Error and acceptable adjusted R-square value. As per the study, analysis of these selected genes is beneficial to diagnose the breast cancer at prior stage in reduced cost and time.

乳腺癌是导致妇女死亡的主要疾病。它是由乳腺癌细胞的基因突变引起的。基因检测已经成为检测基因突变的流行方法,但对于印度等发展中国家的一些患者来说,检测费用相对昂贵。基因测试需要2到4周的时间来确定癌症。由于部分患者癌细胞生长速度快,病程长短受基因预后影响。在研究工作中,提出了一种利用机器学习技术根据患者的临床结果预测基因表达水平的成本和时间效率高的方法。提出了一种改进的SVM-RFE_MI基因选择技术,通过解释方差统计分析提取高方差基因,找到与乳腺癌相关的最显著基因。最小绝对收缩选择算子(LASSO)和岭回归技术用于预测基因表达水平。该方法预测显著基因的表达,具有较低的均方根误差和可接受的调整r平方值。根据研究,分析这些选定的基因有利于在早期诊断乳腺癌,减少了成本和时间。
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引用次数: 7
Cell – extracellular matrix interaction in glioma growth. I n silico model 胶质瘤生长中的细胞-细胞外基质相互作用。I n硅模型
IF 1.9 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1515/jib-2020-0027
V. Kalinin
Abstract The study aims to investigate the role of viscoelastic interactions between cells and extracellular matrix (ECM) in avascular tumor growth. Computer simulations of glioma multicellular tumor spheroid (MTS) growth are being carried out for various conditions. The calculations are based on a continuous model, which simulates oxygen transport into MTS; transitions between three cell phenotypes, cell transport, conditioned by hydrostatic forces in cell–ECM composite system, cell motility and cell adhesion. Visco-elastic cell aggregation and elastic ECM scaffold represent two compressible constituents of the composite. Cell–ECM interactions form a Transition Layer on the spheroid surface, where mechanical characteristics of tumor undergo rapid transition. This layer facilitates tumor progression to a great extent. The study demonstrates strong effects of ECM stiffness, mechanical deformations of the matrix and cell–cell adhesion on tumor progression. The simulations show in particular that at certain, rather high degrees of matrix stiffness a formation of distant multicellular clusters takes place, while at further increase of ECM stiffness subtumors do not form. The model also illustrates to what extent mere mechanical properties of cell–ECM system may contribute into variations of glioma invasion scenarios.
摘要本研究旨在探讨细胞与细胞外基质(ECM)之间的粘弹性相互作用在无血管肿瘤生长中的作用。计算机模拟胶质瘤多细胞肿瘤球体(MTS)的生长正在各种条件下进行。这些计算是基于一个连续模型,该模型模拟氧气向MTS的输送;三种细胞表型之间的转换,细胞运输,由细胞- ecm复合系统中的流体静力调节,细胞运动和细胞粘附。粘弹性细胞聚集体和弹性ECM支架是复合材料的两种可压缩成分。细胞- ecm相互作用在球体表面形成过渡层,肿瘤的力学特性在此发生快速转变。这一层在很大程度上促进了肿瘤的进展。该研究表明,ECM刚度、基质的机械变形和细胞-细胞粘附对肿瘤进展有很强的影响。模拟特别表明,在一定的、相当高的基质刚度下,会形成远端多细胞簇,而在进一步增加ECM刚度时,则不会形成亚肿瘤。该模型还说明了细胞- ecm系统的机械特性在多大程度上可能影响胶质瘤侵袭情景的变化。
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引用次数: 6
期刊
Journal of Integrative Bioinformatics
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