scholarly journals KVarPredDB: a database for predicting pathogenicity of missense sequence variants of keratin genes associated with genodermatoses

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuyi Ying ◽  
Lu Lu ◽  
Santasree Banerjee ◽  
Lizhen Xu ◽  
Qiang Zhao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Web Application ◽  
Functional Characterization ◽  
Dominant Mode ◽  
Heptad Repeat ◽  
Wild Type ◽  
Application Development ◽  
Missense Variants ◽  
Pathogenic Variants ◽  
Development Framework

Abstract Background Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16, and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists. Functional characterization is the only way to understand the clinical association of novel missense variants or VUS but it is time consuming, costly, and depends on the availability of patient’s samples. Existing databases report the pathogenic variants of the keratin genes, but never emphasize the systematic effects of these variants on keratin protein structure and genotype-phenotype correlation. Results To address this need, we developed a comprehensive database KVarPredDB, which contains information of all ten keratin genes associated with genodermatoses. We integrated and curated 400 reported pathogenic missense variants as well as 4629 missense VUS. KVarPredDB predicts the pathogenicity of novel missense variants as well as to understand the severity of disease phenotype, based on four criteria; firstly, the difference in physico-chemical properties between the wild type and substituted amino acids; secondly, the loss of inter/intra-chain interactions; thirdly, evolutionary conservation of the wild type amino acids and lastly, the effect of the substituted amino acids in the heptad repeat. Molecular docking simulations based on resolved crystal structures were adopted to predict stability changes and get the binding energy to compare the wild type protein with the mutated one. We use this basic information to determine the structural and functional impact of novel missense variants on the keratin coiled-coil heterodimer. KVarPredDB was built under the integrative web application development framework SSM (SpringBoot, Spring MVC, MyBatis) and implemented in Java, Bootstrap, React-mutation-mapper, MySQL, Tomcat. The website can be accessed through http://bioinfo.zju.edu.cn/KVarPredDB. The genomic variants and analysis results are freely available under the Creative Commons license. Conclusions KVarPredDB provides an intuitive and user-friendly interface with computational analytical investigation for each missense variant of the keratin genes associated with genodermatoses.

scholarly journals KVarPredDB: A database for predicting pathogenicity of missense sequence variants of keratin genes associated with genodermatoses

2020 ◽  
Author(s):  
Yuyi Ying ◽  
Lu Lu ◽  
Santasree Banerjee ◽  
Lizhen Xu ◽  
Qiang Zhao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Web Application ◽  
Functional Characterization ◽  
Dominant Mode ◽  
Heptad Repeat ◽  
Wild Type ◽  
Application Development ◽  
Missense Variants ◽  
Pathogenic Variants ◽  
Development Framework

Abstract Background: Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16 and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists. Functional characterization is the only way to understand the clinical association of novel missense variants or VUS but it is time-consuming, costly and depends on the availability of patient’s samples. Existing databases report the pathogenic variants of the keratin genes, but never emphasize the systematic effects of these variants on keratin protein structure and genotype-phenotype correlation.Results: To address this need, we developed a comprehensive database KVarPredDB, which contains information of all ten keratin genes associated with genodermatoses. We integrated and curated 400 reported pathogenic missense variants as well as 4629 missense VUS. KVarPredDB predicts the pathogenicity of novel missense variants as well as to understand the severity of disease phenotype, based on four criteria; firstly, difference in physico-chemical properties between the wild-type and substituted amino acids, secondly, the loss of inter/intra-chain interactions, thirdly, evolutionary conservation of the wild type amino acids and lastly, the effect of the substituted amino acids in the heptad repeat. Molecular docking simulations based on resolved crystal structures were adopted to predict stability changes and get the binding energy to compare the wild type protein with the mutated one. We use this basic information to determine the structural and functional impact of novel missense variants on the keratin coiled-coil heterodimer. KVarPredDB was built under the integrative web application development framework SSM (SpringBoot, Spring MVC, MyBatis) and implemented in Java, Bootstrap, React-mutation-mapper, MySQL, Tomcat. The website can be accessed through http://bioinfo.zju.edu.cn/KVarPredDB. The genomic variants and analysis results are freely available under the Creative Commons license.Conclusions: KVarPredDB provides an intuitive and user-friendly interface with computational analytical investigation for each missense variant of the keratin genes associated with genodermatoses.

scholarly journals KVarPredDB: A Database for Predicting Pathogenicity of Missense Sequence Variants of Keratin Genes Associated With Genodermatoses

2020 ◽  
Author(s):  
Santasree Banerjee ◽  
Yuyi Ying ◽  
Lu Lu ◽  
Lizhen Xu ◽  
Qiang Zhao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Web Application ◽  
Functional Characterization ◽  
Dominant Mode ◽  
Heptad Repeat ◽  
Wild Type ◽  
Application Development ◽  
Missense Variants ◽  
Pathogenic Variants ◽  
Development Framework

Abstract Background: Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16 and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists. Functional characterization is the only way to understand the clinical association of novel missense variants or VUS but it is time-consuming, costly and depends on the availability of patient’s samples. Existing databases report the pathogenic variants of the keratin genes, but never emphasize the systematic effects of these variants on keratin protein structure and genotype-phenotype correlation. Results: To address this need, we developed a comprehensive database KVarPredDB, which contains information of all ten keratin genes associated with genodermatoses. We integrated and curated 398 reported pathogenic missense variants as well as 4629 missense VUS. KVarPredDB predicts the pathogenicity of novel missense variants as well as to understand the severity of disease phenotype, based on four criteria; firstly, difference in physico-chemical properties between the wild-type and substituted amino acids, secondly, the loss of inter/intra-chain interactions, thirdly, evolutionary conservation of the wild type amino acids and lastly, the effect of the substituted mutation in the heptad repeat. Molecular docking simulations based on resolved crystal structures were adopted to predict stability changes and get the binding energy to compare the wild type protein with the mutated one. We use this basic information to determine the structural and functional impact of novel missense variants on the keratin coiled-coil heterodimer. KVarPredDB was implemented in Java, Bootstrap, React-mutation-mapper, common MySQL, Tomcat, and under the integrative web application development framework SSM (SpringBoot, Spring MVC, MyBatis). The web site can be accessed through http://bioinfo.zju.edu.cn/KVarPredDB. The genomic variants and analysis results are freely available under the Creative Commons license.Conclusions: KVarPredDB provides an intuitive and user-friendly interface with computational analytical investigation for each missense variant of the keratin genes associated with genodermatoses.

scholarly journals KVarPredDB: A database for predicting pathogenicity of missense sequence variants of keratin genes associated with genodermatoses

2020 ◽  
Author(s):  
Yuyi Ying ◽  
Lu Lu ◽  
Santasree Banerjee ◽  
Lizhen Xu ◽  
Qiang Zhao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Web Application ◽  
Functional Characterization ◽  
Dominant Mode ◽  
Heptad Repeat ◽  
Wild Type ◽  
Application Development ◽  
Missense Variants ◽  
Pathogenic Variants ◽  
Development Framework

Abstract Background: Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16 and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists. Functional characterization is the only way to understand the clinical association of novel missense variants or VUS but it is time-consuming, costly and depends on the availability of patient’s samples. Existing databases report the pathogenic variants of the keratin genes, but never emphasize the systematic effects of these variants on keratin protein structure and genotype-phenotype correlation. Results: To address this need, we developed a comprehensive database KVarPredDB, which contains information of all ten keratin genes associated with genodermatoses. We integrated and curated 400 reported pathogenic missense variants as well as 4629 missense VUS. KVarPredDB predicts the pathogenicity of novel missense variants as well as to understand the severity of disease phenotype, based on four criteria; firstly, difference in physico-chemical properties between the wild-type and substituted amino acids, secondly, the loss of inter/intra-chain interactions, thirdly, evolutionary conservation of the wild type amino acids and lastly, the effect of the substituted amino acids in the heptad repeat. Molecular docking simulations based on resolved crystal structures were adopted to predict stability changes and get the binding energy to compare the wild type protein with the mutated one. We use this basic information to determine the structural and functional impact of novel missense variants on the keratin coiled-coil heterodimer. KVarPredDB was built under the integrative web application development framework SSM (SpringBoot, Spring MVC, MyBatis) and implemented in Java, Bootstrap, React-mutation-mapper, MySQL, Tomcat. The website can be accessed through http://bioinfo.zju.edu.cn/KVarPredDB. The genomic variants and analysis results are freely available under the Creative Commons license.Conclusions: KVarPredDB provides an intuitive and user-friendly interface with computational analytical investigation for each missense variant of the keratin genes associated with genodermatoses.

Spring Framework for Testing

2020 ◽  
Author(s):  
Darshak Mota ◽  
Neel Zadafiya ◽  
Jinan Fiaidhi
Keyword(s):  
Web Application ◽  
Application Development ◽  
Spring Framework ◽  
Java Application ◽  
Development Framework ◽  
Development Life Cycle ◽  
Form Model ◽  
Project Structure ◽  
Model View ◽  
The Web

Java Spring is an application development framework for enterprise Java. It is an open source platform which is used to develop robust Java application easily. Spring can also be performed using MVC structure. The MVC architecture is based on Model View and Controller techniques, where the project structure or code is divided into three parts or sections which helps to categorize the code files and other files in an organized form. Model, View and Controller code are interrelated and often passes and fetches information from each other without having to put all code in a single file which can make testing the program easy. Testing the application while and after development is an integral part of the Software Development Life Cycle (SDLC). Different techniques have been used to test the web application which is developed using Java Spring MVC architecture. And compares the results among all the three different techniques used to test the web application.

A Film Criticism Website Based on “ThinkPHP”

2017 ◽  
Vol 9 (1) ◽  
pp. 1-22
Author(s):  
Sun Zhiyong ◽  
Liu Ye ◽  
Chen JiaHui
Keyword(s):  
Tool Use ◽  
Web Application ◽  
Application Development ◽  
Dynamic Information ◽  
Integrated Development ◽  
Enterprise Application ◽  
Development Framework ◽  
Development Tools ◽  
Web Application Development ◽  
Film Critic

With the continuous development of science and technology and progress of society, the rise of Internet plus era, the cinema began to build their own website in order to expand the film to improve the efficiency, to provide a common discussion for film enthusiasts. This paper uses ThinkPHP framework to complete the needs of the site, it is to simplify the enterprise application development and agile WEB application development and the existence of a fast, compatible and simple lightweight domestic PHP development framework. The analysis in detail on the film critic website in addition, the ThinkPHP framework were analysis explain, on the basis of that tool use is Webstorm development tools with Wamp integrated development tools and environment related structures, database using mysql, ThinkPHP film critic website based on is not only convenient for the users to understand the new release of the news and information, more convenient is that one can allow managers to facilitate the management of a good movie dynamic information and view the user to give the evaluation and so on.

scholarly journals Variant-specific effects define the phenotypic spectrum of HNRNPH2-associated neurodevelopmental disorders in males

2021 ◽  
Author(s):  
Hans-Jürgen Kreienkamp ◽  
Matias Wagner ◽  
Heike Weigand ◽  
Allyn McConkie-Rossell ◽  
Marie McDonald ◽  
...  
Keyword(s):  
De Novo ◽  
Functional Characterization ◽  
Monozygotic Twins ◽  
Rna Recognition Motif ◽  
Neurodevelopmental Delay ◽  
Missense Variants ◽  
Mild Developmental Delay ◽  
Splicing Regulators ◽  
Pathogenic Variants

AbstractBain type of X-linked syndromic intellectual developmental disorder, caused by pathogenic missense variants in HRNRPH2, was initially described in six female individuals affected by moderate-to-severe neurodevelopmental delay. Although it was initially postulated that the condition would not be compatible with life in males, several affected male individuals harboring pathogenic variants in HNRNPH2 have since been documented. However, functional in-vitro analyses of identified variants have not been performed and, therefore, possible genotype–phenotype correlations remain elusive. Here, we present eight male individuals, including a pair of monozygotic twins, harboring pathogenic or likely pathogenic HNRNPH2 variants. Notably, we present the first individuals harboring nonsense or frameshift variants who, similarly to an individual harboring a de novo p.(Arg29Cys) variant within the first quasi-RNA-recognition motif (qRRM), displayed mild developmental delay, and developed mostly autistic features and/or psychiatric co-morbidities. Additionally, we present two individuals harboring a recurrent de novo p.(Arg114Trp), within the second qRRM, who had a severe neurodevelopmental delay with seizures. Functional characterization of the three most common HNRNPH2 missense variants revealed dysfunctional nucleocytoplasmic shuttling of proteins harboring the p.(Arg206Gln) and p.(Pro209Leu) variants, located within the nuclear localization signal, whereas proteins with p.(Arg114Trp) showed reduced interaction with members of the large assembly of splicing regulators (LASR). Moreover, RNA-sequencing of primary fibroblasts of the individual harboring the p.(Arg114Trp) revealed substantial alterations in the regulation of alternative splicing along with global transcriptome changes. Thus, we further expand the clinical and variant spectrum in HNRNPH2-associated disease in males and provide novel molecular insights suggesting the disorder to be a spliceopathy on the molecular level.

A Study on Satisfaction Level Among Amateur Web Application Developers Towards Pigeon-Table as Nano Web Development Framework

2019 ◽  
Vol 31 (3) ◽  
pp. 97-112
Author(s):  
Ong Chin Ann ◽  
Fu Swee Tee ◽  
Voon Yang Nen
Keyword(s):  
Web Application ◽  
Web Applications ◽  
Simple Module ◽  
Web Development ◽  
Web Content ◽  
Application Development ◽  
Development Framework ◽  
Web Application Development ◽  
Using Data ◽  
Application Developers

Web applications are an important platform in today's society, which humans rely on to complete daily tasks. Most of the web applications were developed with sophisticated, well-known, and powerful web development frameworks. While these frameworks evolve and grow at exponential rate, it become very complex, challenging to learn and no longer intuitive for web application developers, especially those who are inexperience and amateur. There is a need for a simpler web development framework which is sufficient for contemporary web application development. Pigeon-table is a simple module developed under ngPigeon project with the aim to generate web content, i.e. table using data from MySQL database with a single html tag. Pigeon-table is intuitive and easy to learn as it was developed with the principle “web developer-centred design” in mind. A pilot test was conducted in this study to evaluate the satisfactory level among amateur web application developers towards pigeon-table as nano-framework.

The Web Development Technology Research of Cross Platform Mobile Application

2014 ◽  
Vol 644-650 ◽  
pp. 3090-3093 ◽  
Author(s):  
Song Sun ◽  
San Xing Cao
Keyword(s):  
Web Application ◽  
Low Cost ◽  
Mobile Internet ◽  
Application Development ◽  
Mobile Web ◽  
Network Applications ◽  
Development Framework ◽  
Development Technology ◽  
Cross Platform ◽  
Interactive Experience

In the current network applications, mobile Internet product development becomes more and more popular, in order to meet the application development of simple, low cost and cross platform adaptation needs, based on the HTML5 technology, jQuery Mobile and PhoneGap development framework, a cross platform development framework based application development model, the mobile Web application implementation of interactive experience comparable to the native applications.

scholarly journals The Heptad Repeat C Domain of the Respiratory Syncytial Virus Fusion Protein Plays a Key Role in Membrane Fusion

2017 ◽  
pp. JVI.01323-17 ◽  
Author(s):  
Imogen M. Bermingham ◽  
Keith J. Chappell ◽  
Daniel Watterson ◽  
Paul R. Young
Keyword(s):  
Amino Acids ◽  
Respiratory Syncytial Virus ◽  
Membrane Fusion ◽  
Functional Characterization ◽  
Proteolytic Processing ◽  
Heptad Repeat ◽  
Alanine Scanning Mutagenesis ◽  
Viral Pathogen ◽  
F Protein ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) mediates host cell entry through the fusion (F) protein, which undergoes a conformational change to facilitate the merger of viral and host lipid membrane envelopes. RSV F comprises a trimer of disulfide bonded F1and F2subunits that is present on the virion surface in a ‘metastable' pre-fusion state. This pre-fusion form is readily triggered to undergo refolding to bring two heptad repeats (HRA and HRB) into close proximity to form a six-helix bundle that stabilizes the post-fusion form and provides the free energy required for membrane fusion. This process can be triggered independently of other proteins. Here, we have performed a comprehensive analysis of a third heptad repeat region, HRC (amino acids 75-97), an amphipathic α-helix that lies at the interface of the pre-fusion F trimer and is a major structural feature of the F2subunit. We performed alanine scanning mutagenesis from Lys-75 to Met-97 and assessed all mutations in transient cell culture for expression, proteolytic processing, cell surface localization, protein conformation and membrane fusion. Functional characterization revealed a striking distribution of activity in which fusion-increasing mutations localized to one side of the helical face, while fusion-decreasing mutations clustered on the opposing face. Herein we propose a model in which HRC plays a stabilizing role within the globular head for the pre-fusion F trimer and is potentially involved in the early events of triggering, prompting fusion peptide release and transition into the post-fusion state.IMPORTANCERSV is recognized as the most important viral pathogen amongst pediatric populations worldwide, yet no vaccine or widely available therapeutic treatment is available. The F protein is critical for the viral replication process and is the major target for neutralizing antibodies. Recent years have seen the development of pre-fusion stabilized F protein based approaches to vaccine design. A detailed understanding of the specific domains and residues that contribute to protein stability and fusion function is fundamental to such efforts. Here we present a comprehensive mutagenesis based study of a region of the RSV F2subunit (amino acids 75 - 97), referred to as HRC, and propose a role for this helical region in maintaining the delicate stability of the pre-fusion form.

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