Next Generation Sequencing in Oncological Diagnostics: Hype or Hope?

The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the transcriptome and the epigenome, besides enabling genome-wide assessment of genetic variations. With the advent of new drugs that are indicated tissue agnostic, depending on certain mutations, there is a growing demand for fast and cost-effective genetic diagnosis. The method in focus that already became an indispensable tool in viral diagnosis is next-generation sequencing (NGS). This approach allows sequencing of literally every DNA molecule in the sample and can either be used to assess numerous genetic markers of one patient at a time, or to assess fewer markers of many patients in parallel, which reduces costs. We submitted 23 samples of different tumor entities to four diagnostic companies with different analysis profiles. The results as disclosed and discussed in this report indicate that so far, the main application of NGS is rather in cancer research than in diagnosis, as none of the reports had a real impact on the therapeutic scheme. We are perfectly aware that such a small cohort cannot be generalized, but considering the costs vs. benefits, NGS should be engaged upon a very stringent evaluation only. However, in cases where obtaining a tissue biopsy is impossible or unfavorable, analysis of liquid biopsy by NGS provides a vital alternative.

A novel PIK3CD C896T mutation detected in bilateral sudden sensorineural hearing loss using next generation sequencing:An indication of primary immunodeficiency

Objective:To investigate immune-related genetic background in bilateral sudden sensorineural hearing loss (SSNHL). Case report and methods: The case is a 45-year-old man presenting with a 7-year history of bilateral profound SSNHL. Blood biochemical testing demonstrated increased levels of total cholesterol (5.88 mmol/L). Tests for hepatitis B showed a positive antibody against the hepatitis B core antigen. Complement C3 was below the normal value, and complement C4 and IgG were in the lower range of normal values. CT images showed a normal inner ear and vestibular aqueduct but round window membranous ossification on both sides. A total number of 232 immune-associated genes were sequenced using the next generation sequencing technique. Results: Mutations were detected in 5 genes, including the phosphoinositide 3-kinase catalytic subunit delta (PIK3CD), caspase recruitment domain-containing protein 9 (CARD9), complement factor H-related (CFHR2), immunoglobulin lambda-like polypeptide 1 Protein (IGLL1), and transmembrane channel-like gene family 8 (TMC8). In the PIK3CD gene, a C896T substitute in exon 7 was detected. This mutation causes primary immunodeficiency and is an autosomal dominant disease. Conclusion: The PIK3CD C896T mutation responsible for primary immunodeficiency may contribute to the onset of bilateral SSNHL with subsequent rapid progression.

Uncertain Multidisciplinary Design Optimization on Next Generation Subsea Production System by Using Surrogate Model and Interval Method

The innovative Next Generation Subsea Production System(NextGen SPS)concept is a newly proposed petroleum development solution in ultra-deep water areas.The definition of NextGen SPS involves several disciplines,which makes the design process difficult.In this paper,the definition of NextGen SPS is modeled as an uncertain multidisciplinary design optimization(MDO)problem.The deterministic optimization model is formulated,and three concerning disciplines—cost calculation,hydrodynamic analysis and global performance analysis are presented.Surrogate model technique is applied in the latter two disciplines.Collaborative optimization(CO)architecture is utilized to organize the concerning disciplines.A deterministic CO framework with two disciplinelevel optimizations is proposed firstly.Then the uncertainties of design parameters and surrogate models are incorporated by using interval method,and uncertain CO frameworks with triple loop and double loop optimization structure are established respectively.The optimization results illustrate that,although the deterministic MDO result achieves higher reduction in objective function than the uncertain MDO result,the latter is more reliable than the former.

Current scenario of the genetic testing for rare neurological disorders exploiting next generation sequencing

Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.

Next Generation Transcriptome Sequencing and Quantitative Real-Time PCR Technologies for Characterisation of the Bemisia tabaci Asia 1 mtCOI Phylogenetic Clade

A programme of functional genomics research is underway at the University of Greenwich,UK,to develop and apply genomics technologies to characterise an economically-important but under-researched Bemisia tabaci（Hemiptera：Aleyrodidae）,the Asia 1 mtCOI phylogenetic group.A comparison of this putative species from India with other important B.tabaci populations and insect species may provide targets for the development of more effective whitefly control strategies.As a first step,next-generation sequencing（NGS）has been used to survey the transcriptome of adult female whitefly,with high quality RNA preparations being used to generate cDNA libraries for NGS using the Roche 454 Titanium DNA sequencing platform.Contig assemblies constructed from the resultant sequences（301 094 reads）using the software program CLC Genomics Workbench generated 3 821 core contigs.Comparison of a selection of these contigs with related sequences from other B.tabaci genetic groups has revealed good alignment for some genes（e.g.,HSP90）but misassemblies in other datasets（e.g.,the vitellogenin gene family）,highlighting the need for manual curation as well as collaborative international efforts to obtain accurate assemblies from the existing next generation sequence datasets.Nevertheless,data emerging from the NGS has facilitated the development of accurate and reliable methods for analysing gene expression based on quantitative real-time RT-PCR,illustrating the power of this approach to enable rapid expression analyses in an organism for which a complete genome sequence is currently lacking.

Forecasting promising technology using analysis of patent information:Focused on next generation mobile communications

In order to forecast promising technologies in the field of next generation mobile communication, various patent indicators were analyzed such as citation per patent, patent family information, patent share, increase rate, and patent activity. These indicators were quantified into several indexes and then integrated into an evaluation score to provide promising technologies. As a result of the suggested patent analysis, four technologies out of twenty two in details classification were selected, which showed outstanding technology competitiveness, high patent share and increasing rates as well as high recent-patent-ratios and triad-patent-family-ratios. Each of the selected technologies scored more than 10 points in total, and the following four technologies were suggested as promising ones in the field of next generation mobile communication: 1) 3GPP based mobile communication, 2) beyond 4G mobile communication, 3) IEEE 802.16 based mobile communication, which are in medium classification of broadband mobile communication system, and 4) testing/certification system of mobile communication, which is in medium classification of mobile communication testing/certification system.

Trusted Next Generation Internetand Its Development

The ongoing research on secure and trustworthy issues in next generation Internet technology is still insufficient. China has achieved some progress in the field of the trusted next generation Internet. Under the support of the National High Technology Research and Development Program of China (863 Program), Tsinghua University and other units have completed the program named 'Research on Critical Technologies and Demonstration Applications of the Trusted Next Generation Internet', which targets the secure and trustworthy problems existing in the current Internet. With focus on tackling the technical problem of authentic address access in the Internet, a prototype system for trusted Internet infrastructure, security service and typical applications are designed and implemented. It is expected that the trusted next generation Internet will support the trusted computer network, trusted telecom network and trusted broadcast & TV network applications.

Universal Intelligent Small Cell （UnISCell） for next generation cellular networks

Exploring innovative cellular architectures to achieve enhanced system capacity and good coverage has become a critical issue towards realizing the next generation of wireless communications. In this context, this paper proposes a novel concept of Universal Intelligent Small Cell （UnISCell） for enabling the densification of the next generation of cellular networks. The proposed novel concept envisions an integrated platform of providing a strong linkage between different stakeholders such as street lighting networks, landline telephone networks and future wireless networks, and is universal in nature being independent of the operating frequency bands and traffic types. The main motivating factors for the proposed small cell concept are the need of public infrastructure re-engineering, and the recent advances in several enabling technologies. First, we highlight the main concepts of the proposed UnISCell platform. Subsequently, we present two deployment scenarios for the proposed UnISCell concept considering infrastructure sharing and service sharing as important aspects. We then describe the key future technologies for enabling the proposed UnISCell concept and present a use case example with the help of numerical results. Finally, we conclude this article by providing some interesting future recommendations.

The ethics of exercise in eating disorders:Can an ethical principles approach guide the next generation of research and clinical practice?

1.Introduction Eating disorders(ED)are the most common psychiatric disorders afflicting young women^1 and contribute to great detriments in psychological,social,and physical health.^(2,3)Unfortunately,ED treatments tend to be long lasting,intensive,and expensive.~4Additionally,individuals with ED seeking treatment use healthcare services more frequently than non-ED individu-

Fecal gene detection based on next generation sequencing for colorectal cancer diagnosis

BACKGROUND Colorectal cancer(CRC)is one of the most common malignancies worldwide.Given its insidious onset,the condition often already progresses to advanced stage when symptoms occur.Thus,early diagnosis is of great significance for timely clinical intervention,efficacy enhancement,and prognostic improvement.Featuring high throughput,fastness,and rich information,next generation sequencing(NGS)can greatly shorten the detection time,which is a widely used detection technique at present.AIM To screen specific genes or gene combinations in fecal DNA that are suitable for diagnosis and prognostic prediction of CRC,and to establish a technological platform for CRC screening,diagnosis,and efficacy monitoring through fecal DNA detection.METHODS NGS was used to sequence the stool DNA of patients with CRC,which were then compared with the genetic testing results of the stool samples of normal controls and patients with benign intestinal disease,as well as the tumor tissues of CRC patients.Specific genes or gene combinations in fecal DNA suitable for diagnosis and prognostic prediction of CRC were screened,and their significances in diagnosing CRC and predicting patients'prognosis were comprehensively evaluated.RESULTS High mutation frequencies of TP53,APC,and KRAS were detected in the stools and tumor tissues of CRC patients prior to surgery.Contrastively,no pathogenic mutations of the above three genes were noted in the postoperative stools,the normal controls,or the benign intestinal disease group.This indicates that tumor-specific DNA was detectable in the preoperative stools of CRC patients.The preoperative fecal expression of tumor-associated genes can reflect the gene mutations in tumor tissues to some extent.Compared to the postoperative stools and the stools in the two control groups,the pathogenic mutation frequencies of TP53 and KRAS were significantly higher for the preoperative stools(χ^(2)=7.328,P<0.05;χ^(2)=4.219,P<0.05),suggesting that fecal TP53 and KRAS genes can be used for CRC screening,diagnosis,and prognostic prediction.No significant difference in the pathogenic mutation frequency of the APC gene was found from the postoperative stools or the two control groups(χ^(2)=0.878,P>0.05),so further analysis with larger sample size is required.Among CRC patients,the pathogenic mutation sites of TP53 occurred in 16 of 27 preoperative stools,with a true positive rate of 59.26%,while the pathogenic mutation sites of KRAS occurred in 10 stools,with a true positive rate of 37.04%.The sensitivity and negative predictive values of the combined genetic testing of TP53 and KRAS were 66.67%(18/27)and 68.97%,respectively,both of which were higher than those of TP53 or KRAS mutation detection alone,suggesting that the combined genetic testing can improve the CRC detection rate.The mutation sites TP53 exon 4 A84G and EGFR exon 20 I821T(mutation start and stop positions were both 7579436 for the former,while 55249164 for the latter)were found in the preoperative stools and tumor tissues.These"undetected"mutation sites may be new types of mutations occurring during the CRC carcinogenesis and progression,which needs to be confirmed through further research.Some mutations of"unknown clinical significance"were found in such genes as TP53,PTEN,KRAS,BRAF,AKT1,and PIK3CA,whose clinical values is worthy of further exploration.CONCLUSION NGS-based fecal genetic testing can be used as a complementary technique for the CRC diagnosis.Fecal TP53 and KRAS can be used as specific genes for the screening,diagnosis,prognostic prediction,and recurrence monitoring of CRC.Moreover,the combined testing of TP53 and KRAS genes can improve the CRC detection rate.

Development of IPv6 Capabilities for Next Generation Internet

The IPv6-powered Internet will cover not only its data communication market, but also the voice-service-dominant fixed-line and mobile markets. The fresh markets of video communication for recreational/educational purposes and information household appliance networking are also on the horizon. In other words, IPv6 means new revenue resources for telecom carriers.

Next Generation Network Enabled by ZTE's Softswitch Technology

Softswitch technology integrates the su-periorities of both an intelligence net-work and the Internet, which embodiesits maturity and advancement. With ahierarchical network model, it effectivelysolves problems of evolution and convergenceof current communication networks. It also fol-

Strategic Thinking on Next Generation Network

It is noted that the revolutionary development of technologies,fundamental change of traffic composition,trend of network convergence as well as market opening and competition have become the driving forces to develop Next Generation Networks (NGN).After introducing the concepts and characteristics of NGN,the paper details its 5 strategic development directions:evolution to softswitch-based next generation switching network, evolution to next generation mobile communication network represented by 3G,evolution to IPv6-based next generation Internet,evolution to diversified broadband access network,and evolution to next generation transport network based on optical networking.Finally,it briefs the strategic thinking on NGN of China Telecom,the largest fixed network carrier in the world.

Next Generation Network Service Provision Mode and Its Developing Trend

The provision mode of the telecommunication service has experienced an evolving process, and showing the developing trend from distributed to centralized, from integrated to separated, and from closed to open. To suit this trend, there will be three provision modes as Session Initiation Protocol (SIP) server, Open Service Access (OSA) application server and intelligent network(IN) in Next Generation Network (NGN), provides all kinds of services and applications to the subscribers. With the popularity of broadband access and Internet, the NGN will provide single telecommunication service and act as the important national infrastructure to offer various information services to the subscribers. The service provision mode will be more open, diversified, and individualized.

Next Generation Mobile Video Networking

HWANG Jenq-Neng received his Ph.D. degree from the University of Southern California, USA. In the summer of 1989, Dr. HWANG joined the De- partment of Electrical Engineering of the Universi- ty of Washington in Seattle, USA, where he has been promoted to Full Professor since 1999. He served as the Associate Chair for Research fi＇om 2003 to 2005, and from 2011-2015. He is current- ly the Associate Chair for Global Affairs and Inter- national Development in the EE Depamnent. Hehas written more than 330 journal papers, conference papers and book chapters in the areas of machine learning, muhimedia signal processing, and muhimedia system integration and networking, including an au- thored textbook on ＂Multimedia Networking： from Theory to Practice,＂ published by Cambridge University Press. Dr. HWANG has close work- ing relationship with the industry on muhimedia signal processing and nmltimedia networking.

Service Convergence in Next Generation Network

The convergence of communication services becomes a focus in the industry along with the requirement for full-service operation and technical development. Service convergence includes two aspects: The convergence of the fixed and mobile networks; and the convergence of traditional communications and Internet services. This requires balancing the conflicts between the openness and operationability of terminal capability and network convergence. Unified authentication and authorization are the basis for service convergence in terms of operationability. Modular network and open terminal are technical solutions for the service convergence.

Wavelet Neural Network Based Traffic Prediction for Next Generation Network

By using netflow traffic collecting technology, some traffic data for analysis are collected from a next generation network （NGN） operator. To build a wavelet basis neural network （NN）, the Sigmoid function is replaced with the wavelet in NN. Then the wavelet multiresolution analysis method is used to decompose the traffic signal, and the decomposed component sequences are employed to train the NN. By using the methods, an NGN traffic prediction model is built to predict one day＇s traffic. The experimental results show that the traffic prediction method of wavelet NN is more accurate than that without using wavelet in the NGN traffic forecasting.

ZTE's Solution to China Next Generation Internet (CNGI)

Today IPv6 is the hottest topic worldwide. Many countries are positively impelling the research and application of the Next Generation Internet (NGI). China launched a large scale IPv6 backbone network project: China Next Generation Internet (CNGI). This article introduces the birth of IPv6 and CNGI, then discusses ZTE's solution to CNGI in detail.

Next Generation Network

Next Generation Network(NGN)is not a single architecture but a set of architectures with a common set of principles and hence varies by service provider history,target applications and assets.The paper introduces NGN functional requirements,NGN services and NGN architectural features.It also discusses why NGN is needed,when NGN is targeted,NGN trends and NGN deployment.It concludes that it is no longer a case whether NGN is needed but rather when and at what speed of the evolution.

ZTE Announces Next Generation 3G Data Card

ZTE Corporation (ZTE) announced on February 16,2009 that their complete line of mobile broadband data cards would support Windows 7 and be compliant with the Windows Network Driver Interface Specification 6.20,NDIS6.20.