Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,...Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.展开更多
Background:As reported by the World Health Organization,a novel coronavirus(2019-nCoV)was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January,2020.The virus was...Background:As reported by the World Health Organization,a novel coronavirus(2019-nCoV)was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January,2020.The virus was named as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)by International Committee on Taxonomy of Viruses on 11 February,2020.This study aimed to develop a mathematical model for calculating the transmissibility of the virus.Methods:In this study,we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source(probably be bats)to the human infection.Since the Bats-HostsReservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market(reservoir)to people,we simplified the model as Reservoir-People(RP)transmission network model.The next generation matrix approach was adopted to calculate the basic reproduction number(R0)from the RP model to assess the transmissibility of the SARS-CoV-2.Results:The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.Conclusions:Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries,similar to severe acute respiratory syndrome,but lower than MERS in the Republic of Korea.展开更多
Brain and the gastrointestinal(GI)tract are intimately con-nected to form a bidirectional neurohumoral communica-tion system.The communication between gut and brain,knows as the gut-brain axis,is so well established t...Brain and the gastrointestinal(GI)tract are intimately con-nected to form a bidirectional neurohumoral communica-tion system.The communication between gut and brain,knows as the gut-brain axis,is so well established that the functional status of gut is always related to the condi-tion of brain.The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract.However,recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes.These recent fi ndings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis.To elucidate the role of gut microbiota in the gut-brain axis,precise identification of the composition of microbes constituting gut microbiota is an essential step.However,identifi cation of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the diffi culties in culture of gut microbes.Current methods for identifi ca-tion of microbes constituting gut microbiota are depend-ent on omics analysis methods by using advanced high tech equipment.Here,we review the association of gut microbiota with the gut-brain axis,including the pros and cons of the current high throughput methods for identi-fi cation of microbes constituting gut microbiota to eluci-date the role of gut microbiota in the gut-brain axis.展开更多
This article reviews basic concepts, general applications, and the potential impact of next-generation sequencing （NGS） technologies on genomics, with particular reference to currently available and possible future ...This article reviews basic concepts, general applications, and the potential impact of next-generation sequencing （NGS） technologies on genomics, with particular reference to currently available and possible future platforms and bioinformatics. NGS technologies have demon- strated the capacity to sequence DNA at unprecedented speed, thereby enabling previously unimaginable scientific achievements and novel biological applications. But, the massive data produced by NGS also presents a significant challenge for data storage, analyses, and management solutions. Advanced bioinformatic tools are essential for the successful application of NGS technology. As evidenced throughout this review, NGS technologies will have a striking impact on genomic research and the entire biological field. With its ability to tackle the unsolved challenges unconquered by previous genomic technologies, NGS is likely to unravel the complexity of the human genome in terms of genetic variations, some of which may be confined to susceptible loci for some common human conditions. The impact of NGS technologies on genomics will be far reaching and likely change the field for years to come.展开更多
BACKGROUND: The study aims to investigate the performance of a metagenomic next-generationsequencing (NGS)-based diagnostic technique for the identifi cation of potential bacterial and viral infectionsand eff ects of ...BACKGROUND: The study aims to investigate the performance of a metagenomic next-generationsequencing (NGS)-based diagnostic technique for the identifi cation of potential bacterial and viral infectionsand eff ects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients.METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for bloodcultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded.The correlations between pathogen types and sepsis severity and survival rate were evaluated.RESULTS: NGS produced higher positive results (105 of 118;88.98%) than blood cultures(18 of 118;15.25%) over the whole study period. Concomitant viral infection correlated closelywith sepsis severity and had the negative effect on the survival of patients with sepsis. However,correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis.CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and thesurvival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviraldrugs combined with antibiotics may be benefi cial to ICU sepsis patients.展开更多
In 2005, the US passed the Energy Policy Act of 2005 mandating the construction and operation of a high-temperature gas reactor （HTGR） by 2021. This law was passed after a multiyear study by national experts on what...In 2005, the US passed the Energy Policy Act of 2005 mandating the construction and operation of a high-temperature gas reactor （HTGR） by 2021. This law was passed after a multiyear study by national experts on what future nuclear technologies should be developed. As a result of the Act, the US Congress chose to develop the so-called Next-Generation Nuclear Plant, which was to be an HTGR designed to produce process heat for hydrogen production. Despite high hopes and expectations, the current status is that high temperature reactors have been relegated to completing research programs on advanced fuels, graphite and materials with no plans to build a demonstration plant as required by the US Con- gress in 2005. There are many reasons behind this diminution of HTGR development, including but not limited to insufficient government funding requirements for research, unrealistically high temperature requirements for the reactor, the delay in the need for a ＂hydrogen＂ economy, competition from light water small modular light water reactors, little utility interest in new technologies, very low natural gas prices in the US, and a challenging licensing process in the US for non-water reactors.展开更多
Understanding the relationship between genotype and phenotype is a major biological question and being able to predict phenotypes based on molecular genotypes is integral to molecular breeding. Whole- genome duplicati...Understanding the relationship between genotype and phenotype is a major biological question and being able to predict phenotypes based on molecular genotypes is integral to molecular breeding. Whole- genome duplications have shaped the history of all flowering plants and present challenges to elucidating the relationship between genotype and phenotype, especially in neopolyploid species. Although single nucleotide polymorphisms （SNPs） have become popular tools for genetic mapping, discovery and appli- cation of SNPs in polyploids has been difficult. Here, we summarize common experimental approaches to SNP calling, highlighting recent polyploid successes. To examine the impact of software choice on these analyses, we called SNPs among five peanut genotypes using different alignment programs （BWA-mem and Bowtie 2） and variant callers （SAMtools, GATK, and Freebayes）. Alignments produced by Bowtie 2 and BWA-mem and analyzed in SAMtools shared 24.5% concordant SNPs, and SAMtools, GATK, and Freebayes shared 1.4% concordant SNPs. A subsequent analysis of simulated Brassica napus chromosome 1A and 1C genotypes demonstrated that, of the three software programs, SAMtools performed with the highest sensitivity and specificity on Bowtie 2 alignments. These results, however, are likely to vary among species, and we therefore propose a series of best practices for SNP calling in polyploids.展开更多
An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January eFebruary 2020.Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers an...An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January eFebruary 2020.Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members,we characterize how the transmission potential varied over the course of the outbreak.Our estimate of the mean reproduction number in the confined setting reached values as high as^11,which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore(approximate range:1.1e7).Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control.Most recent estimates of Rt reached values largely below the epidemic threshold,indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.展开更多
Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
Next-generation sequencing （NGS） technology, with its high-throughput capacity and low cost, has developed rapidly in recent years and become an important analytical tool for many genomics researchers. New opportuni...Next-generation sequencing （NGS） technology, with its high-throughput capacity and low cost, has developed rapidly in recent years and become an important analytical tool for many genomics researchers. New opportunities in the research domain of the forensic studies emerge by harnessing the power of NGS technology, which can be applied to simultaneously analyzing multi- ple loci of forensic interest in different genetic contexts, such as autosomes, mitochondrial and sex chromosomes. Furthermore, NGS technology can also have potential applications in many other aspects of research. These include DNA database construction, ancestry and phenotypic inference, monozygotic twin studies, body fluid and species identification, and forensic animal, plant and microbiological analyses. Here we review the application of NGS technology in the field of forensic science with the aim of providing a reference for future forensics studies and practice.展开更多
Transcriptomics is one of the most developed fields in the post-genomic era.Transcriptome is the complete set of RNA transcripts in a specific cell type or tissue at a certain developmental stage and/or under a specif...Transcriptomics is one of the most developed fields in the post-genomic era.Transcriptome is the complete set of RNA transcripts in a specific cell type or tissue at a certain developmental stage and/or under a specific physiological condition,including messenger RNA,transfer RNA,ribosomal RNA,and other non-coding RNAs.Transcriptomics focuses on the gene expression at the RNA level and offers the genome-wide information of gene structure and gene function in order to reveal the molecular mechanisms involved in specific biological processes.With the development of next-generation high-throughput sequencing technology,transcriptome analysis has been progressively improving our understanding of RNA-based gene regulatory network.Here,we discuss the concept,history,and especially the recent advances in this inspiring field of study.展开更多
Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy samp...Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA （15 pg） and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification （MDA） system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing （CNV-Seq） was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient＇s cohort for uterine transplantation,展开更多
RNA-Seq technology is becoming widely used in various transcriptomics studies;however,analyzing and interpreting the RNA-Seq data face serious challenges.With the development of high-throughput sequencing technologies...RNA-Seq technology is becoming widely used in various transcriptomics studies;however,analyzing and interpreting the RNA-Seq data face serious challenges.With the development of high-throughput sequencing technologies,the sequencing cost is dropping dramatically with the sequencing output increasing sharply.However,the sequencing reads are still short in length and contain various sequencing errors.Moreover,the intricate transcriptome is always more complicated than we expect.These challenges proffer the urgent need of efficient bioinformatics algorithms to effectively handle the large amount of transcriptome sequencing data and carry out diverse related studies.This review summarizes a number of frequently-used applications of transcriptome sequencing and their related analyzing strategies,including short read mapping,exon-exon splice junction detection,gene or isoform expression quantification,differential expression analysis and transcriptome reconstruction.展开更多
Many viruses can cause respiratory diseases in humans.Although great advances have been achieved in methods of diagnosis,it remains challenging to identify pathogens in unexplained pneumonia(UP) cases.In this study,we...Many viruses can cause respiratory diseases in humans.Although great advances have been achieved in methods of diagnosis,it remains challenging to identify pathogens in unexplained pneumonia(UP) cases.In this study,we applied next-generation sequencing(NGS) technology and a metagenomic approach to detect and characterize respiratory viruses in UP cases from Guizhou Province,China.A total of 33 oropharyngeal swabs were obtained from hospitalized UP patients and subjected to NGS.An unbiased metagenomic analysis pipeline identified 13 virus species in 16 samples.Human rhinovirus C was the virus most frequently detected and was identified in seven samples.Human measles virus,adenovirus B 55 and coxsackievirus A10 were also identified.Metagenomic sequencing also provided virus genomic sequences,which enabled genotype characterization and phylogenetic analysis.For cases of multiple infection,metagenomic sequencing afforded information regarding the quantity of each virus in the sample,which could be used to evaluate each viruses' role in the disease.Our study highlights the potential of metagenomic sequencing for pathogen identification in UP cases.展开更多
Background： The dilemma of pathogens identification in patients with unidentified clinical symptoms such as lever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic proc...Background： The dilemma of pathogens identification in patients with unidentified clinical symptoms such as lever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic process by itself, but also to expert physicians. Methods： In this report, we have attempted to increase the awareness of unidentified pathogens by developing a method to investigate hitherto unidentified infectious pathogens based on unbiased high-throughput sequencing. Results： Our observations show that this method supplements current diagnostic technology that predominantly relies on information derived five cases from the intensive care unit. This methodological approach detects viruses and corrects the incidence of false positive detection rates of pathogens in a much shorter period. Through our method is followed by polymerase chain reaction validation, we could identify infection with Epstein-Barr virus, and in another case, we could identify infection with Streptococcus viridians based on the culture, which was false positive. Conclusions： This technology is a promising approach to revolutionize rapid diagnosis of infectious pathogens and to guide therapy that might result in the improvement of personalized medicine.展开更多
基金This study was supported by grants from the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2016-I2M-1-014)the National Major Science&Technology Project for Control and Prevention of Major Infectious Diseases in China(Nos.2017ZX10103004,2018ZX10305409,2017ZX10204401)the National Natural Science Foundation(No.81930063)
文摘Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
基金This study was supported by Xiamen New Coronavirus Prevention and Control Emergency Tackling Special Topic Program(No:3502Z2020YJ03).
文摘Background:As reported by the World Health Organization,a novel coronavirus(2019-nCoV)was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January,2020.The virus was named as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)by International Committee on Taxonomy of Viruses on 11 February,2020.This study aimed to develop a mathematical model for calculating the transmissibility of the virus.Methods:In this study,we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source(probably be bats)to the human infection.Since the Bats-HostsReservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market(reservoir)to people,we simplified the model as Reservoir-People(RP)transmission network model.The next generation matrix approach was adopted to calculate the basic reproduction number(R0)from the RP model to assess the transmissibility of the SARS-CoV-2.Results:The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.Conclusions:Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries,similar to severe acute respiratory syndrome,but lower than MERS in the Republic of Korea.
文摘Brain and the gastrointestinal(GI)tract are intimately con-nected to form a bidirectional neurohumoral communica-tion system.The communication between gut and brain,knows as the gut-brain axis,is so well established that the functional status of gut is always related to the condi-tion of brain.The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract.However,recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes.These recent fi ndings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis.To elucidate the role of gut microbiota in the gut-brain axis,precise identification of the composition of microbes constituting gut microbiota is an essential step.However,identifi cation of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the diffi culties in culture of gut microbes.Current methods for identifi ca-tion of microbes constituting gut microbiota are depend-ent on omics analysis methods by using advanced high tech equipment.Here,we review the association of gut microbiota with the gut-brain axis,including the pros and cons of the current high throughput methods for identi-fi cation of microbes constituting gut microbiota to eluci-date the role of gut microbiota in the gut-brain axis.
基金supported by NINDS/NIH(JZ),Coldwell Foundation(JZ) and TTUHSC(JZ)
文摘This article reviews basic concepts, general applications, and the potential impact of next-generation sequencing （NGS） technologies on genomics, with particular reference to currently available and possible future platforms and bioinformatics. NGS technologies have demon- strated the capacity to sequence DNA at unprecedented speed, thereby enabling previously unimaginable scientific achievements and novel biological applications. But, the massive data produced by NGS also presents a significant challenge for data storage, analyses, and management solutions. Advanced bioinformatic tools are essential for the successful application of NGS technology. As evidenced throughout this review, NGS technologies will have a striking impact on genomic research and the entire biological field. With its ability to tackle the unsolved challenges unconquered by previous genomic technologies, NGS is likely to unravel the complexity of the human genome in terms of genetic variations, some of which may be confined to susceptible loci for some common human conditions. The impact of NGS technologies on genomics will be far reaching and likely change the field for years to come.
基金supported by grants from Scienceand Technology Committee of Shanghai (18411951400)KeyClinical Medical Specialties Project in Shanghai Pudong NewArea (PWZzk2017-22)+1 种基金Science and Technology Action Plan(19495810200)Leading Talent Project in Shanghai Pudong NewArea Health System (PWRl2018-08).
文摘BACKGROUND: The study aims to investigate the performance of a metagenomic next-generationsequencing (NGS)-based diagnostic technique for the identifi cation of potential bacterial and viral infectionsand eff ects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients.METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for bloodcultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded.The correlations between pathogen types and sepsis severity and survival rate were evaluated.RESULTS: NGS produced higher positive results (105 of 118;88.98%) than blood cultures(18 of 118;15.25%) over the whole study period. Concomitant viral infection correlated closelywith sepsis severity and had the negative effect on the survival of patients with sepsis. However,correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis.CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and thesurvival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviraldrugs combined with antibiotics may be benefi cial to ICU sepsis patients.
文摘In 2005, the US passed the Energy Policy Act of 2005 mandating the construction and operation of a high-temperature gas reactor （HTGR） by 2021. This law was passed after a multiyear study by national experts on what future nuclear technologies should be developed. As a result of the Act, the US Congress chose to develop the so-called Next-Generation Nuclear Plant, which was to be an HTGR designed to produce process heat for hydrogen production. Despite high hopes and expectations, the current status is that high temperature reactors have been relegated to completing research programs on advanced fuels, graphite and materials with no plans to build a demonstration plant as required by the US Con- gress in 2005. There are many reasons behind this diminution of HTGR development, including but not limited to insufficient government funding requirements for research, unrealistically high temperature requirements for the reactor, the delay in the need for a ＂hydrogen＂ economy, competition from light water small modular light water reactors, little utility interest in new technologies, very low natural gas prices in the US, and a challenging licensing process in the US for non-water reactors.
文摘Understanding the relationship between genotype and phenotype is a major biological question and being able to predict phenotypes based on molecular genotypes is integral to molecular breeding. Whole- genome duplications have shaped the history of all flowering plants and present challenges to elucidating the relationship between genotype and phenotype, especially in neopolyploid species. Although single nucleotide polymorphisms （SNPs） have become popular tools for genetic mapping, discovery and appli- cation of SNPs in polyploids has been difficult. Here, we summarize common experimental approaches to SNP calling, highlighting recent polyploid successes. To examine the impact of software choice on these analyses, we called SNPs among five peanut genotypes using different alignment programs （BWA-mem and Bowtie 2） and variant callers （SAMtools, GATK, and Freebayes）. Alignments produced by Bowtie 2 and BWA-mem and analyzed in SAMtools shared 24.5% concordant SNPs, and SAMtools, GATK, and Freebayes shared 1.4% concordant SNPs. A subsequent analysis of simulated Brassica napus chromosome 1A and 1C genotypes demonstrated that, of the three software programs, SAMtools performed with the highest sensitivity and specificity on Bowtie 2 alignments. These results, however, are likely to vary among species, and we therefore propose a series of best practices for SNP calling in polyploids.
文摘An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January eFebruary 2020.Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members,we characterize how the transmission potential varied over the course of the outbreak.Our estimate of the mean reproduction number in the confined setting reached values as high as^11,which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore(approximate range:1.1e7).Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control.Most recent estimates of Rt reached values largely below the epidemic threshold,indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81172909 and 81330073)
文摘Next-generation sequencing （NGS） technology, with its high-throughput capacity and low cost, has developed rapidly in recent years and become an important analytical tool for many genomics researchers. New opportunities in the research domain of the forensic studies emerge by harnessing the power of NGS technology, which can be applied to simultaneously analyzing multi- ple loci of forensic interest in different genetic contexts, such as autosomes, mitochondrial and sex chromosomes. Furthermore, NGS technology can also have potential applications in many other aspects of research. These include DNA database construction, ancestry and phenotypic inference, monozygotic twin studies, body fluid and species identification, and forensic animal, plant and microbiological analyses. Here we review the application of NGS technology in the field of forensic science with the aim of providing a reference for future forensics studies and practice.
基金supported by grants from the National Natural Science Foundation of China(31271318)Natural Science Foundation of Guangdong(S2012010008912)Foundation of Key Laboratory of Plant Resources Conservation and Sustainable Utilization,South China Botanical Garden,Chinese Academy of Sciences
文摘Transcriptomics is one of the most developed fields in the post-genomic era.Transcriptome is the complete set of RNA transcripts in a specific cell type or tissue at a certain developmental stage and/or under a specific physiological condition,including messenger RNA,transfer RNA,ribosomal RNA,and other non-coding RNAs.Transcriptomics focuses on the gene expression at the RNA level and offers the genome-wide information of gene structure and gene function in order to reveal the molecular mechanisms involved in specific biological processes.With the development of next-generation high-throughput sequencing technology,transcriptome analysis has been progressively improving our understanding of RNA-based gene regulatory network.Here,we discuss the concept,history,and especially the recent advances in this inspiring field of study.
基金supported by grants awarded to Yuanqing Yao by the Key Program of the "Twelfth Five-year plan" of People’s liberation Army(No.BWS11J058)the National High Technology Research and Development Program(SS2015AA020402)
文摘Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA （15 pg） and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification （MDA） system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing （CNV-Seq） was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient＇s cohort for uterine transplantation,
基金supported by the National Basic Research Program of China (Grant Nos. 2010CB945401, 2007CB108800)National Natural Science Foundation of China (Grant Nos. 30870575,31071162,31000590)Science and Technology Commission of Shanghai Municipality (Grant No. 11DZ2260300)
文摘RNA-Seq technology is becoming widely used in various transcriptomics studies;however,analyzing and interpreting the RNA-Seq data face serious challenges.With the development of high-throughput sequencing technologies,the sequencing cost is dropping dramatically with the sequencing output increasing sharply.However,the sequencing reads are still short in length and contain various sequencing errors.Moreover,the intricate transcriptome is always more complicated than we expect.These challenges proffer the urgent need of efficient bioinformatics algorithms to effectively handle the large amount of transcriptome sequencing data and carry out diverse related studies.This review summarizes a number of frequently-used applications of transcriptome sequencing and their related analyzing strategies,including short read mapping,exon-exon splice junction detection,gene or isoform expression quantification,differential expression analysis and transcriptome reconstruction.
基金supported by the National Mega-projects for Infectious Diseases(2014ZX10004002)Beijing Municipal Science and Technology Commission grant(D151100002115003)
文摘Many viruses can cause respiratory diseases in humans.Although great advances have been achieved in methods of diagnosis,it remains challenging to identify pathogens in unexplained pneumonia(UP) cases.In this study,we applied next-generation sequencing(NGS) technology and a metagenomic approach to detect and characterize respiratory viruses in UP cases from Guizhou Province,China.A total of 33 oropharyngeal swabs were obtained from hospitalized UP patients and subjected to NGS.An unbiased metagenomic analysis pipeline identified 13 virus species in 16 samples.Human rhinovirus C was the virus most frequently detected and was identified in seven samples.Human measles virus,adenovirus B 55 and coxsackievirus A10 were also identified.Metagenomic sequencing also provided virus genomic sequences,which enabled genotype characterization and phylogenetic analysis.For cases of multiple infection,metagenomic sequencing afforded information regarding the quantity of each virus in the sample,which could be used to evaluate each viruses' role in the disease.Our study highlights the potential of metagenomic sequencing for pathogen identification in UP cases.
文摘Background： The dilemma of pathogens identification in patients with unidentified clinical symptoms such as lever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic process by itself, but also to expert physicians. Methods： In this report, we have attempted to increase the awareness of unidentified pathogens by developing a method to investigate hitherto unidentified infectious pathogens based on unbiased high-throughput sequencing. Results： Our observations show that this method supplements current diagnostic technology that predominantly relies on information derived five cases from the intensive care unit. This methodological approach detects viruses and corrects the incidence of false positive detection rates of pathogens in a much shorter period. Through our method is followed by polymerase chain reaction validation, we could identify infection with Epstein-Barr virus, and in another case, we could identify infection with Streptococcus viridians based on the culture, which was false positive. Conclusions： This technology is a promising approach to revolutionize rapid diagnosis of infectious pathogens and to guide therapy that might result in the improvement of personalized medicine.
