AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55...AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55 eyes)with postoperative endophthalmitis were retrospectively included in this study with their medical records.Intraocular fluid samples were examined by NTS and microbial culture.All included patients had undergone examinations including measurement of best corrected visual acuity(BCVA)and intraocular pressure(IOP),slit-lamp biomicroscopy,and indirect ophthalmoscopy;additionally,they underwent B-ultrasound,anterior segment photography,and fundus photography if necessary.RESULTS:Among 55 patients with postoperative endophthalmitis,the age was 65.25±15.04y and there were 30 female(54.54%)patients.Forty-one(74.54%)vitreous humor samples and fourteen(25.45%)aqueous humor samples were sent for both NTS and microbial culture.NTS had a notable higher detection rate than microbial culture in detecting pathogens(90.91%vs 38.18%,χ^(2)=33.409,P<0.001).NTS exhibited high sensitivity of pathogen detection in both microbial culture positive and negative samples(100%and 85.29%,respectively).In 16 of 21(76.19%)patients who showed culture-positivity,their results corresponded with those of NTS.Moreover,in two patients(9.52%),NTS showed a better species resolution than microbial culture;in three patients(14.28%),NTS identified additional pathogens.As for fungus,the positive detection rate of NTS was significantly higher than that of microbial culture(20%vs 3.64%,χ^(2)=7.066,P=0.008).Also,NTS could detect multi-infection by bacteria and fungi than microbial culture(32.73%vs 0,χ^(2)=21.522,P<0.001).NTS could detect bacteria as well as fungi simultaneously within 48h in all patients.Meanwhile,NTS had a shorter detection time than microbial culture(1.13±0.34 vs 2.67±0.55d,Z=-9.218,P<0.001).After the NTS results were obtained,15 patients received additional intravitreal/intracameral anti-infection treatment.At follow-up,there was a statistically significant improvement in the visual acuity relative to the baseline(Z=−5.222,P<0.001).CONCLUSION:NTS can provide rapid identification and highly sensitive detection of pathogens among patients with postoperative endophthalmitis,which can guide anti-infection treatment and improve visual prognosis.展开更多
Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 46...Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.展开更多
China’s newborn screening(NBS)system,initiated over four decades ago with dual-disease detection[phenylketonuria(PKU)and congenital hypothyroidism(CH)],has progressively expanded to encompass congenital adrenocortica...China’s newborn screening(NBS)system,initiated over four decades ago with dual-disease detection[phenylketonuria(PKU)and congenital hypothyroidism(CH)],has progressively expanded to encompass congenital adrenocortical hyperplasia(CAH)and glucose-6-phosphate dehydrogenase(G6PD)deficiency,achieving nationwide universal coverage.This systematic progression has substantially elevated diagnostic rates for these disorders,enabling timely therapeutic interventions[1].Over the past two decades,technological innovations—notably the integration of tandem mass spectrometry(MS/MS)platforms in pioneering regions such as Shanghai and Zhejiang—have extended NBS to over 40 inherited metabolic diseases(IMDs).展开更多
Background:Infective endocarditis(IE)and myocarditis are serious heart diseases that can lead to life-threatening complications.These illnesses can have infectious origins,including viral,bacterial,or fungal pathogens...Background:Infective endocarditis(IE)and myocarditis are serious heart diseases that can lead to life-threatening complications.These illnesses can have infectious origins,including viral,bacterial,or fungal pathogens.Traditional detection methods,such as culture-based methods,have limited ability to detect causative pathogens because of antibiotic use and the difficulty in cultivating intracellular and fastidious bacteria as well as viruses.In clinical settings,rapid diagnostics for pathogen identification are essential for timely treatment and appropriate antimicrobial therapy.Methods:We successfully developed a method based on nanopore targeted sequencing(NTS)with pathogen-specific panels for testing myocarditis and IE.As part of this pilot study,a sample-to-results protocol was developed with an optimized in-house pipeline and bioinformatics analysis solution.Results:The performance of NTS met our expectations for sensitivity,specificity,and turnaround time.The pathogen-specific panel testing was accomplished in a 10-h turnaround time,achieving a detection limit of 20 copies/test for the IE target panel and 10 copies/test for the myocarditis target panel.NTS achieved a clinical performance of 85.0% sensitivity and 96.3% specificity compared with culture testing methods,using 74 clinical specimens from patients(53 male,21 female)associated with IE.Conclusions:The rapid turnaround time of NTS is advantageous for managing acute infections,such as IE and myocarditis.NTS is a powerful tool for rapidly diagnosing infections in IE and myocarditis with significant potential for broader clinical applications.展开更多
Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritiz...Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases.In this study,a Chinese woman,presenting with characteristic facial features of KS,came for pre-pregnancy consultation.We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling.Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants,respectively.The candidate variant was verified by Sanger sequencing.We identified a novel de novo KDM6A pathogenic variant(c.3521G>A)in the woman,which was in line with the Face2Gene analysis result.Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A.Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.展开更多
46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have ...46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have been found.However,the clinical phenotypes of patients with different gene mutations overlap,and accurate diagnosis relies on gene sequencing technology.Therefore,this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted nextgeneration sequencing(NGS)technology.Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital(Beijing,China).A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD.The incidence of these rare variants was approximately 69.0%(60/87).Twenty-five novel variants and 29 reported variants were identified.Based on the American College of Medical Genetics and Genomics(ACMG)guidelines,thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance.The overall diagnostic rate was about 42.5%based on the pathogenic and likely pathogenic variants.Androgen receptor{AR),steroid 5-alpha-reductase 2(SRD5A2)and nuclear receptor subfamily 5 Group A member 1(NR5A1)gene variants were identified in 21,13 and 13 patients,respectively.The incidence of these three gene variants was about 78.3%(47/60)in patients with rare variants.It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR,SRD5A2,and NR5A1 genes were the most common pathogenic genes in our cohort.展开更多
Objective This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing(tNGS)of bronchoalveolar lavage fluid(BALF)in pulmonary mycobacterial infections.Methods This retrospect...Objective This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing(tNGS)of bronchoalveolar lavage fluid(BALF)in pulmonary mycobacterial infections.Methods This retrospective study was conducted on patients who underwent bronchoscopy and tNGS,smear microscopy,and mycobacterial culture of BALF.Patients with positive Mycobacterium tuberculosis(MTB)culture or GeneXpert results were classified into the tuberculosis case group.Those diagnosed with nontuberculous mycobacteria(NTM)-pulmonary disease(NTM-PD)composed the case group of NTM-PD patients.The control group comprised patients without tuberculosis or NTM-PD.Sensitivity,specificity,and receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance.Results For tuberculosis patients with positive mycobacterial culture results,the areas under the ROC curves(AUCs)for tNGS,GeneXpert,and smear microscopy were 0.975(95%CI:0.935,1.000),0.925(95%CI:0.859,0.991),and 0.675(95%CI:0.563,0.787),respectively.For tuberculosis patients with positive GeneXpert results,the AUCs of tNGS,culture,and smear microscopy were 0.970(95%CI:0.931,1.000),0.850(95%CI:0.770,0.930),and 0.680(95%CI:0.579,0.781),respectively.For NTM-PD,the AUCs of tNGS,culture,and smear-positive but GeneXpert-negative results were 0.987(95%CI:0.967,1.000),0.750(95%CI:0.622,0.878),and 0.615(95%CI:0.479,0.752),respectively.The sensitivity and specificity of tNGS in NTM-PD patients were 100%and 97.5%,respectively.Conclusion tNGS demonstrated superior diagnostic efficacy in mycobacterial infection,indicating its potential for clinical application.展开更多
Owing to the limitation of a large genome size(~13 Gb),the genetic and gene mapping studies on faba bean(Vicia faba L.)are lagging far behind those for other legumes.In this study,we selected three purified faba bean ...Owing to the limitation of a large genome size(~13 Gb),the genetic and gene mapping studies on faba bean(Vicia faba L.)are lagging far behind those for other legumes.In this study,we selected three purified faba bean lines(Yundou 8137,H0003712,and H000572)as parents and constructed two F2 populations.These two F2 populations,namely 167 F2 plants in Pop1(Yundou 8137×H0003712)and 204 F2 plants in Pop2(H000572×Yundou 8137),were genotyped using a targeted next-generation sequencing(TNGS)genotyping platform,and two high-density single nucleotide polymorphisms(SNP)genetic linkage maps of faba bean were constructed.The map constructed from Pop1 contained 5103 SNPs with a length of 1333.31 cM and an average marker density of 0.26 cM.The map constructed from Pop2 contained 1904 SNPs with a greater length of 1610.61 cM.In these two F2 populations,QTL mapping identified 98 QTLs for 14 agronomic traits related to the flowers,pods,plant types and grains.The two maps were then merged into an integrated genetic linkage map containing 6895 SNPs,with a length of 3324.48 cM.These results not only lay the foundation for fine mapping and map-based cloning of related genes,but can also accelerate the molecular marker-assisted breeding of faba bean.展开更多
Genotyping by target sequencing(GBTS)integrates the advantages of silicon-based technology(high stability and reliability)and genotyping by sequencing(high flexibility and cost-effectiveness).However,GBTS panels are n...Genotyping by target sequencing(GBTS)integrates the advantages of silicon-based technology(high stability and reliability)and genotyping by sequencing(high flexibility and cost-effectiveness).However,GBTS panels are not currently available in pigs.In this study,based on GBTS technology,we first developed a 50K panel,including 52,000 single-nucleotide polymorphisms(SNPs),in pigs,designated GBTS50K.A total of 6,032 individuals of Large White,Landrace,and Duroc pigs from 10 breeding farms were used to assess the newly developed GBTS50K.Our results showed that GBTS50K obtained a high genotyping ability,the SNP and individual call rates of GBTS50K were 0.997–0.998,and the average consistency rate and genotyping correlation coefficient were 0.997 and 0.993,respectively,in replicate samples.We also evaluated the efficiencies of GBTS50K in the application of population genetic structure analysis,selection signature detection,genome-wide association studies(GWAS),genotyped imputation,genetic selection(GS),etc.The results indicate that GBTS50K is plausible and powerful in genetic analysis and molecular breeding.For example,GBTS50K could gain higher accuracies than the current popular GGP-Porcine bead chip in genomic selection on 2 important traits of backfat thickness at 100 kg and days to 100 kg in pigs.Particularly,due to the multiple SNPs(mSNPs),GBTS50K generated 100K qualified SNPs without increasing genotyping cost,and our results showed that the haplotype-based method can further improve the accuracies of genomic selection on growth and reproduction traits by 2 to 6%.Our study showed that GBTS50K could be a powerful tool for underlying genetic architecture and molecular breeding in pigs,and it is also helpful for developing SNP panels for other farm animals.展开更多
Genotyping by Target Sequencing(GBTS)technology,known for its flexibility,high efficiency,high throughput,and low cost,has been increasingly employed in molecular breeding.However,there is still limited study on the d...Genotyping by Target Sequencing(GBTS)technology,known for its flexibility,high efficiency,high throughput,and low cost,has been increasingly employed in molecular breeding.However,there is still limited study on the design and development of high-throughput genotyping tools in watermelon.In this study,we identified 112000 high quality SNPs by analyzing the resequencing data of 43 cultivated watermelon accessions.11921 and 6094 SNPs were selected for developing two sets of watermelon liquid-phase chips with different marker densities,named Watermelon 10K and 5K,respectively.Furthermore,the SNPs and Indels of most mapped gene/QTLs for many agronomic important traits in watermelon were also integrated into the two chips for foreground selection.These chips have been tested using GBTS technology in various applications in watermelon.The genotyping of 76 accessions by Watermelon 5K liquid-phase chip showed an average detection rate of 99.28%and 81.78%for cultivated and wild watermelon accessions,respectively.This provided enough markers information for GWAS and two significant QTLs,ssc1.1 and ssc1.2,associated with soluble sugar content were detected.Furthermore,BSA-seq analysis for non-lobed leaf and dwarf traits were validated by liquid-phase chips,and the candidate region was consistent with our previous studies.Additionally,we precisely introduced the Cldw1 and Clbl genes into an elite inbred line WT2 using Watermelon 5K for assisted selection,resulting in the development of three new germplasm with good plant architecture.As a high-throughput genotyping liquid-phase SNP array,the Watermelon 10K and 5K chips will greatly facilitate functional studies and molecular breeding in watermelon.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
AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 20...AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 2015.Firstly,whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found,and then homozygous sites was selected,candidate sites were annotated,and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant（SIFT）,Polyphen-2,Mutation assessor,Condel,and Functional Analysis through Hidden Markov Models（FATHMM）.Furthermore,Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test.Sanger sequencing was used to validate single-nucleotide variations（SNVs）.Expanded verification was performed in the rest patients.RESULTS：Totally 51 LCA families with 53 patients and24 family members were recruited.A total of 104 SNVs（66 LCA-related genes and 15 co-segregated genes）were submitted for expand verification.The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families.Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion,biological adhesion,retinoid metabolic process,and eye development biological adhesion.Additionally,WFS7 and STAU2 had the highest homozygous frequencies.CONCLUSION：LCA is a highly heterogeneous disease.Mutations in KRT12,CVP1A1,WFS1,and STAU2 may be involved in the development of LCA.展开更多
Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to...Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.展开更多
The expanding application of targeted next-generation sequencing(tNGS)in clinical diagnostics has led to an increasing frequency of Nocardia spp.detection in respiratory specimens;however,the clinical relevance and in...The expanding application of targeted next-generation sequencing(tNGS)in clinical diagnostics has led to an increasing frequency of Nocardia spp.detection in respiratory specimens;however,the clinical relevance and interpretation of these findings remain uncertain.This study describes the epidemiology of Nocardia pneumonia and colonization in patients at The University of Hong Kong–Shenzhen Hospital,China,and evaluates the diagnostic role of tNGS.The analysis was conducted from January 2023 through December 2024 and included 22 patients in whom Nocardia spp.were detected in respiratory specimens via tNGS.Among these patients,81.8%(18/22)had comorbidities,most commonly chronic lung disease(40.9%,9/22).Common clinical symptoms included cough,sputum and fever.Nocardia farcinica and Nocardia abscessus were the predominant species identified.Although the median number of se-quence reads of Nocardia were higher in infected patients than in colonized individuals(289,IQR:132.5–3747 vs.133.5,IQR:51.75–261.3),the difference was not statistically significant(P>0.05).In a comparison of diagnostic performance,tNGS identified Nocardia sequences in all 25 respiratory samples collected from the enrolled patients,whereas conventional aerobic culture success-fully isolated the pathogen in only two patients.Additionally,tNGS exhibited a significantly shorter median turnaround time than culture(38 h vs.376.5 h).These findings highlight tNGS as a rapid tool for Nocardia detection.However,the final diagnosis of nocardiosis can-not rely solely on sequence read thresholds.Clinical,radiological and laboratory integration remains critical in distinguishing true infection from colonization,ensuring accurate diagnosis and management of nocardiosis.展开更多
Space target imaging simulation technology is an important tool for space target detection and identification,with advantages that include high flexibility and low cost.However,existing space target imaging simulation...Space target imaging simulation technology is an important tool for space target detection and identification,with advantages that include high flexibility and low cost.However,existing space target imaging simulation technologies are mostly based on target magnitudes for simulations,making it difficult to meet image simulation requirements for different signal-to-noise ratio(SNR)needs.Therefore,design of a simulation method that generates target image sequences with various SNRs based on the optical detection system parameters will be important for faint space target detection research.Addressing the SNR calculation issue in optical observation systems,this paper proposes a ground-based detection image SNR calculation method using the optical system parameters.This method calculates the SNR of an observed image precisely using radiative transfer theory,the optical system parameters,and the observation environment parameters.An SNR-based target sequence image simulation method for ground-based detection scenarios is proposed.This method calculates the imaging SNR using the optical system parameters and establishes a model for conversion between the target’s apparent magnitude and image grayscale values,thereby enabling generation of target sequence simulation images with corresponding SNRs for different system parameters.Experiments show that the SNR obtained using this calculation method has an average calculation error of<1 dB when compared with the theoretical SNR of the actual optical system.Additionally,the simulation images generated by the imaging simulation method show high consistency with real images,which meets the requirements of faint space target detection algorithm research and provides reliable data support for development of related technologies.展开更多
Introduction:Vaccination stands as the most effective preventive measure against yellow fever(YF).However,the YF vaccination associated Adverse Events following Immunization(AEFI)cases occur occasionally.Methods:The G...Introduction:Vaccination stands as the most effective preventive measure against yellow fever(YF).However,the YF vaccination associated Adverse Events following Immunization(AEFI)cases occur occasionally.Methods:The Guangdong Provincial Center for Disease Control and Prevention utilized Targeted Next-Generation Sequencing(tNGS)to determine whether the imported suspected YF case was infected by the wild-type YF virus strain or experienced an AEFI.Results:tNGS analysis successfully yielded a 10.2 kb viral genomic sequence.Subsequent in-depth analysis revealed high similarity to the YF vaccine strain 17D-213 and classified the sequence within the West Africa II genotype,clustering with the 17D vaccine strain.Conclusions and Implications for Public Health Practice:This case represented YF AEFI.The implementation of tNGS technology enables more precise and expeditious pathogen sequencing,providing critical evidence for accurate disease diagnosis and informed public health interventions.展开更多
Endophthalmitis is a serious ophthalmic disease characterized by changes in the eye's posterior segment,such as hypopyon and intraocular inflammation,vitritis being a hallmark.Infection-caused endophthalmitis can ...Endophthalmitis is a serious ophthalmic disease characterized by changes in the eye's posterior segment,such as hypopyon and intraocular inflammation,vitritis being a hallmark.Infection-caused endophthalmitis can lead to irreversible vision loss,accompanied by eye pain or eye distention,and in the most severe cases the removal of the eyeball.Microorganisms such as bacteria,fungi,viruses,and parasites typically account for the disease and the entry pathways of the microbial can be divided into either endogenous or exogenous approaches,according to the origin of the etiological agents.Exogenous endophthalmitis can be derived from various occasions(such as postoperative complications or trauma)while endogenous endophthalmitis results from the bloodstream which carries pathogens to the eye.This review aims to summarize the application of new technology in pathogen identification of endophthalmitis so as to prevent the disease and better guide clinical diagnosis and treatment.展开更多
Previous studies have demonstrated that Chinese lung adenocarcinoma(LUAD)patients have unique genetic characteristics,however,the specific genomic features relating to the development and treatment of LUAD in the Chin...Previous studies have demonstrated that Chinese lung adenocarcinoma(LUAD)patients have unique genetic characteristics,however,the specific genomic features relating to the development and treatment of LUAD in the Chinese population are not fully understood.Here,we applied the ultra-deep targeted sequencing to 66 Chinese LUAD samples,accompanied by comparative analysis with 162 Caucasian LUAD in The Cancer Genome Atlas.We focused on the 68 recurrently mutated genes and results revealed that the panel-based tumor mutational burden(pTMB)is significantly higher in the Chinese LUAD(P=0.0017).Additionally,the percentage of smoking-associated C>A transversion is significantly lower in Chinese LUAD(15.5%vs.39.7%,P=5.69×10^(-27)),while C>T transition is more frequent in Chinese LUAD(35.8%vs.25.7%,P=2.67×10^(-5)),which indicated the ethnic difference in mutation types.Notably,novel driver genes(GNAS and JAK1)that are peculiar to Chinese LUAD were identified,and a more convergent distribution of mutations was observed in the Chinese cohort(P=0.012)compared with scattered mutations in Caucasian LUAD.Our results present a distinct genomic profile of Chinese LUAD compared to Caucasians LUAD and elucidate the ethnic difference in mutation distribution besides the type and rate.展开更多
基金Supported by Open Project of Key Laboratory of Hubei Province(No.2023KFZZ026).
文摘AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55 eyes)with postoperative endophthalmitis were retrospectively included in this study with their medical records.Intraocular fluid samples were examined by NTS and microbial culture.All included patients had undergone examinations including measurement of best corrected visual acuity(BCVA)and intraocular pressure(IOP),slit-lamp biomicroscopy,and indirect ophthalmoscopy;additionally,they underwent B-ultrasound,anterior segment photography,and fundus photography if necessary.RESULTS:Among 55 patients with postoperative endophthalmitis,the age was 65.25±15.04y and there were 30 female(54.54%)patients.Forty-one(74.54%)vitreous humor samples and fourteen(25.45%)aqueous humor samples were sent for both NTS and microbial culture.NTS had a notable higher detection rate than microbial culture in detecting pathogens(90.91%vs 38.18%,χ^(2)=33.409,P<0.001).NTS exhibited high sensitivity of pathogen detection in both microbial culture positive and negative samples(100%and 85.29%,respectively).In 16 of 21(76.19%)patients who showed culture-positivity,their results corresponded with those of NTS.Moreover,in two patients(9.52%),NTS showed a better species resolution than microbial culture;in three patients(14.28%),NTS identified additional pathogens.As for fungus,the positive detection rate of NTS was significantly higher than that of microbial culture(20%vs 3.64%,χ^(2)=7.066,P=0.008).Also,NTS could detect multi-infection by bacteria and fungi than microbial culture(32.73%vs 0,χ^(2)=21.522,P<0.001).NTS could detect bacteria as well as fungi simultaneously within 48h in all patients.Meanwhile,NTS had a shorter detection time than microbial culture(1.13±0.34 vs 2.67±0.55d,Z=-9.218,P<0.001).After the NTS results were obtained,15 patients received additional intravitreal/intracameral anti-infection treatment.At follow-up,there was a statistically significant improvement in the visual acuity relative to the baseline(Z=−5.222,P<0.001).CONCLUSION:NTS can provide rapid identification and highly sensitive detection of pathogens among patients with postoperative endophthalmitis,which can guide anti-infection treatment and improve visual prognosis.
基金partially supported by grants from the Ministry of Science and Technology of China(2016YFC1000306)the Beijing Municipal Science and Technology Commission Foundation(Z181100001918003)+1 种基金the Beijing Municipal Commission of Health and Family Planning Foundation(2018-21141,2020-4-1144)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201905)。
文摘Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.
基金funded by Innovation Foundation of Jinan Clinical Medicine Science and Technology(202225012).
文摘China’s newborn screening(NBS)system,initiated over four decades ago with dual-disease detection[phenylketonuria(PKU)and congenital hypothyroidism(CH)],has progressively expanded to encompass congenital adrenocortical hyperplasia(CAH)and glucose-6-phosphate dehydrogenase(G6PD)deficiency,achieving nationwide universal coverage.This systematic progression has substantially elevated diagnostic rates for these disorders,enabling timely therapeutic interventions[1].Over the past two decades,technological innovations—notably the integration of tandem mass spectrometry(MS/MS)platforms in pioneering regions such as Shanghai and Zhejiang—have extended NBS to over 40 inherited metabolic diseases(IMDs).
基金funded by the National Key R&D Program of China(grant number:2018YFF01012105).
文摘Background:Infective endocarditis(IE)and myocarditis are serious heart diseases that can lead to life-threatening complications.These illnesses can have infectious origins,including viral,bacterial,or fungal pathogens.Traditional detection methods,such as culture-based methods,have limited ability to detect causative pathogens because of antibiotic use and the difficulty in cultivating intracellular and fastidious bacteria as well as viruses.In clinical settings,rapid diagnostics for pathogen identification are essential for timely treatment and appropriate antimicrobial therapy.Methods:We successfully developed a method based on nanopore targeted sequencing(NTS)with pathogen-specific panels for testing myocarditis and IE.As part of this pilot study,a sample-to-results protocol was developed with an optimized in-house pipeline and bioinformatics analysis solution.Results:The performance of NTS met our expectations for sensitivity,specificity,and turnaround time.The pathogen-specific panel testing was accomplished in a 10-h turnaround time,achieving a detection limit of 20 copies/test for the IE target panel and 10 copies/test for the myocarditis target panel.NTS achieved a clinical performance of 85.0% sensitivity and 96.3% specificity compared with culture testing methods,using 74 clinical specimens from patients(53 male,21 female)associated with IE.Conclusions:The rapid turnaround time of NTS is advantageous for managing acute infections,such as IE and myocarditis.NTS is a powerful tool for rapidly diagnosing infections in IE and myocarditis with significant potential for broader clinical applications.
基金supported by the National Natural Science Foundation of China(No.81471506,81401219,81501276,and 81771638)the National Key Research and Development Program of China(No.2016YFC0905103)+4 种基金the Shanghai Municipal Commission of Science and Technology Program,China(No.15411966700,15411964000,and 17411972900)the Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai,China(No.2018YQ39)the Shanghai Municipal Commission of Health and Family Planning Program,China(No.20154Y0039 and 15GWZK0701)the Shanghai Jiao Tong University Program,China(No.YG2017MS39)the Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine,Shanghai SJTUSM Biobank,China(No.15ZH4011).
文摘Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases.In this study,a Chinese woman,presenting with characteristic facial features of KS,came for pre-pregnancy consultation.We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling.Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants,respectively.The candidate variant was verified by Sanger sequencing.We identified a novel de novo KDM6A pathogenic variant(c.3521G>A)in the woman,which was in line with the Face2Gene analysis result.Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A.Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.
基金This work was supported by the National Natural Science Foundation of China(No.81971375 and No.81771576)the National Key Research and Development Program of China(2016YFC0905100)+1 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1-002)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2017PT32020 and No.2018PT32001).
文摘46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have been found.However,the clinical phenotypes of patients with different gene mutations overlap,and accurate diagnosis relies on gene sequencing technology.Therefore,this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted nextgeneration sequencing(NGS)technology.Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital(Beijing,China).A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD.The incidence of these rare variants was approximately 69.0%(60/87).Twenty-five novel variants and 29 reported variants were identified.Based on the American College of Medical Genetics and Genomics(ACMG)guidelines,thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance.The overall diagnostic rate was about 42.5%based on the pathogenic and likely pathogenic variants.Androgen receptor{AR),steroid 5-alpha-reductase 2(SRD5A2)and nuclear receptor subfamily 5 Group A member 1(NR5A1)gene variants were identified in 21,13 and 13 patients,respectively.The incidence of these three gene variants was about 78.3%(47/60)in patients with rare variants.It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR,SRD5A2,and NR5A1 genes were the most common pathogenic genes in our cohort.
文摘Objective This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing(tNGS)of bronchoalveolar lavage fluid(BALF)in pulmonary mycobacterial infections.Methods This retrospective study was conducted on patients who underwent bronchoscopy and tNGS,smear microscopy,and mycobacterial culture of BALF.Patients with positive Mycobacterium tuberculosis(MTB)culture or GeneXpert results were classified into the tuberculosis case group.Those diagnosed with nontuberculous mycobacteria(NTM)-pulmonary disease(NTM-PD)composed the case group of NTM-PD patients.The control group comprised patients without tuberculosis or NTM-PD.Sensitivity,specificity,and receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance.Results For tuberculosis patients with positive mycobacterial culture results,the areas under the ROC curves(AUCs)for tNGS,GeneXpert,and smear microscopy were 0.975(95%CI:0.935,1.000),0.925(95%CI:0.859,0.991),and 0.675(95%CI:0.563,0.787),respectively.For tuberculosis patients with positive GeneXpert results,the AUCs of tNGS,culture,and smear microscopy were 0.970(95%CI:0.931,1.000),0.850(95%CI:0.770,0.930),and 0.680(95%CI:0.579,0.781),respectively.For NTM-PD,the AUCs of tNGS,culture,and smear-positive but GeneXpert-negative results were 0.987(95%CI:0.967,1.000),0.750(95%CI:0.622,0.878),and 0.615(95%CI:0.479,0.752),respectively.The sensitivity and specificity of tNGS in NTM-PD patients were 100%and 97.5%,respectively.Conclusion tNGS demonstrated superior diagnostic efficacy in mycobacterial infection,indicating its potential for clinical application.
基金supported by the National Key R&D Program of China(2019YFD1001300 and 2019YFD1001303)the Construction of Molecular Database of Faba Bean and Pea and Identification of Maize Germplasm Project,Ministry of Agriculture and Rural Affairs,China(19200030)+3 种基金the Yunnan Key R&D Program,China(202202AE090003)the earmarked fund for China Agriculture Research System(CARS-08)the Crop Germplasm Resources Protection(2130135)the Major Agricultural Science and Technology Program of Chinese Academy of Agricultural Sciences(CAAS-XTCX20190025)。
文摘Owing to the limitation of a large genome size(~13 Gb),the genetic and gene mapping studies on faba bean(Vicia faba L.)are lagging far behind those for other legumes.In this study,we selected three purified faba bean lines(Yundou 8137,H0003712,and H000572)as parents and constructed two F2 populations.These two F2 populations,namely 167 F2 plants in Pop1(Yundou 8137×H0003712)and 204 F2 plants in Pop2(H000572×Yundou 8137),were genotyped using a targeted next-generation sequencing(TNGS)genotyping platform,and two high-density single nucleotide polymorphisms(SNP)genetic linkage maps of faba bean were constructed.The map constructed from Pop1 contained 5103 SNPs with a length of 1333.31 cM and an average marker density of 0.26 cM.The map constructed from Pop2 contained 1904 SNPs with a greater length of 1610.61 cM.In these two F2 populations,QTL mapping identified 98 QTLs for 14 agronomic traits related to the flowers,pods,plant types and grains.The two maps were then merged into an integrated genetic linkage map containing 6895 SNPs,with a length of 3324.48 cM.These results not only lay the foundation for fine mapping and map-based cloning of related genes,but can also accelerate the molecular marker-assisted breeding of faba bean.
基金supported by the grants from the Key R&D Program of Shandong Province,China(2022LZGC003)the China Agriculture Research System of MOF and MARA(CARS-35)+1 种基金the National Key Research and Development Project of China(2019YFE0106800)the 2115 Talent Development Program of China Agricultural University。
文摘Genotyping by target sequencing(GBTS)integrates the advantages of silicon-based technology(high stability and reliability)and genotyping by sequencing(high flexibility and cost-effectiveness).However,GBTS panels are not currently available in pigs.In this study,based on GBTS technology,we first developed a 50K panel,including 52,000 single-nucleotide polymorphisms(SNPs),in pigs,designated GBTS50K.A total of 6,032 individuals of Large White,Landrace,and Duroc pigs from 10 breeding farms were used to assess the newly developed GBTS50K.Our results showed that GBTS50K obtained a high genotyping ability,the SNP and individual call rates of GBTS50K were 0.997–0.998,and the average consistency rate and genotyping correlation coefficient were 0.997 and 0.993,respectively,in replicate samples.We also evaluated the efficiencies of GBTS50K in the application of population genetic structure analysis,selection signature detection,genome-wide association studies(GWAS),genotyped imputation,genetic selection(GS),etc.The results indicate that GBTS50K is plausible and powerful in genetic analysis and molecular breeding.For example,GBTS50K could gain higher accuracies than the current popular GGP-Porcine bead chip in genomic selection on 2 important traits of backfat thickness at 100 kg and days to 100 kg in pigs.Particularly,due to the multiple SNPs(mSNPs),GBTS50K generated 100K qualified SNPs without increasing genotyping cost,and our results showed that the haplotype-based method can further improve the accuracies of genomic selection on growth and reproduction traits by 2 to 6%.Our study showed that GBTS50K could be a powerful tool for underlying genetic architecture and molecular breeding in pigs,and it is also helpful for developing SNP panels for other farm animals.
基金supported by the National Natural Science Foundation of China(Grant Nos.32172602,32472739)the Major Science and Technology Project of Henan Province(Grant No.221100110400)+3 种基金the Funding of Joint Research on Agricultural Varietie Improvement of Henan Province(Grant No.2022010503)the Natural Science Foundation of Henan(Grant No.242300421030)the Key Scientifc and Technological Project of Henan Province(Grant Nos.242102111124,242102111115)the Key Research and Development Program of Xinjiang Uygur autonomous region(2023B02017-2).
文摘Genotyping by Target Sequencing(GBTS)technology,known for its flexibility,high efficiency,high throughput,and low cost,has been increasingly employed in molecular breeding.However,there is still limited study on the design and development of high-throughput genotyping tools in watermelon.In this study,we identified 112000 high quality SNPs by analyzing the resequencing data of 43 cultivated watermelon accessions.11921 and 6094 SNPs were selected for developing two sets of watermelon liquid-phase chips with different marker densities,named Watermelon 10K and 5K,respectively.Furthermore,the SNPs and Indels of most mapped gene/QTLs for many agronomic important traits in watermelon were also integrated into the two chips for foreground selection.These chips have been tested using GBTS technology in various applications in watermelon.The genotyping of 76 accessions by Watermelon 5K liquid-phase chip showed an average detection rate of 99.28%and 81.78%for cultivated and wild watermelon accessions,respectively.This provided enough markers information for GWAS and two significant QTLs,ssc1.1 and ssc1.2,associated with soluble sugar content were detected.Furthermore,BSA-seq analysis for non-lobed leaf and dwarf traits were validated by liquid-phase chips,and the candidate region was consistent with our previous studies.Additionally,we precisely introduced the Cldw1 and Clbl genes into an elite inbred line WT2 using Watermelon 5K for assisted selection,resulting in the development of three new germplasm with good plant architecture.As a high-throughput genotyping liquid-phase SNP array,the Watermelon 10K and 5K chips will greatly facilitate functional studies and molecular breeding in watermelon.
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 National Natural Science Foundation of China(No.81470642No.81271045)
文摘AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 2015.Firstly,whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found,and then homozygous sites was selected,candidate sites were annotated,and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant（SIFT）,Polyphen-2,Mutation assessor,Condel,and Functional Analysis through Hidden Markov Models（FATHMM）.Furthermore,Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test.Sanger sequencing was used to validate single-nucleotide variations（SNVs）.Expanded verification was performed in the rest patients.RESULTS：Totally 51 LCA families with 53 patients and24 family members were recruited.A total of 104 SNVs（66 LCA-related genes and 15 co-segregated genes）were submitted for expand verification.The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families.Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion,biological adhesion,retinoid metabolic process,and eye development biological adhesion.Additionally,WFS7 and STAU2 had the highest homozygous frequencies.CONCLUSION：LCA is a highly heterogeneous disease.Mutations in KRT12,CVP1A1,WFS1,and STAU2 may be involved in the development of LCA.
基金supported by the National Natural Science Foundation of China(No.82003561).
文摘Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.
基金supported by the Health Commission of Shenzhen Municipality under the Sanming Project of Medicine(SZSM201911014)in Shenzhenthe High Level-Hospital Program,Health Commission of Guangdong Province,China.
文摘The expanding application of targeted next-generation sequencing(tNGS)in clinical diagnostics has led to an increasing frequency of Nocardia spp.detection in respiratory specimens;however,the clinical relevance and interpretation of these findings remain uncertain.This study describes the epidemiology of Nocardia pneumonia and colonization in patients at The University of Hong Kong–Shenzhen Hospital,China,and evaluates the diagnostic role of tNGS.The analysis was conducted from January 2023 through December 2024 and included 22 patients in whom Nocardia spp.were detected in respiratory specimens via tNGS.Among these patients,81.8%(18/22)had comorbidities,most commonly chronic lung disease(40.9%,9/22).Common clinical symptoms included cough,sputum and fever.Nocardia farcinica and Nocardia abscessus were the predominant species identified.Although the median number of se-quence reads of Nocardia were higher in infected patients than in colonized individuals(289,IQR:132.5–3747 vs.133.5,IQR:51.75–261.3),the difference was not statistically significant(P>0.05).In a comparison of diagnostic performance,tNGS identified Nocardia sequences in all 25 respiratory samples collected from the enrolled patients,whereas conventional aerobic culture success-fully isolated the pathogen in only two patients.Additionally,tNGS exhibited a significantly shorter median turnaround time than culture(38 h vs.376.5 h).These findings highlight tNGS as a rapid tool for Nocardia detection.However,the final diagnosis of nocardiosis can-not rely solely on sequence read thresholds.Clinical,radiological and laboratory integration remains critical in distinguishing true infection from colonization,ensuring accurate diagnosis and management of nocardiosis.
基金supported by Open Fund of National Key Laboratory of Deep Space Exploration(NKDSEL2024014)by Civil Aerospace Pre-research Project of State Administration of Science,Technology and Industry for National Defence,PRC(D040103).
文摘Space target imaging simulation technology is an important tool for space target detection and identification,with advantages that include high flexibility and low cost.However,existing space target imaging simulation technologies are mostly based on target magnitudes for simulations,making it difficult to meet image simulation requirements for different signal-to-noise ratio(SNR)needs.Therefore,design of a simulation method that generates target image sequences with various SNRs based on the optical detection system parameters will be important for faint space target detection research.Addressing the SNR calculation issue in optical observation systems,this paper proposes a ground-based detection image SNR calculation method using the optical system parameters.This method calculates the SNR of an observed image precisely using radiative transfer theory,the optical system parameters,and the observation environment parameters.An SNR-based target sequence image simulation method for ground-based detection scenarios is proposed.This method calculates the imaging SNR using the optical system parameters and establishes a model for conversion between the target’s apparent magnitude and image grayscale values,thereby enabling generation of target sequence simulation images with corresponding SNRs for different system parameters.Experiments show that the SNR obtained using this calculation method has an average calculation error of<1 dB when compared with the theoretical SNR of the actual optical system.Additionally,the simulation images generated by the imaging simulation method show high consistency with real images,which meets the requirements of faint space target detection algorithm research and provides reliable data support for development of related technologies.
基金Supported by the Guangdong Provincial Key Laboratory of Pathogen Detection for Emerging Infectious Disease Response(2023B1212010010).
文摘Introduction:Vaccination stands as the most effective preventive measure against yellow fever(YF).However,the YF vaccination associated Adverse Events following Immunization(AEFI)cases occur occasionally.Methods:The Guangdong Provincial Center for Disease Control and Prevention utilized Targeted Next-Generation Sequencing(tNGS)to determine whether the imported suspected YF case was infected by the wild-type YF virus strain or experienced an AEFI.Results:tNGS analysis successfully yielded a 10.2 kb viral genomic sequence.Subsequent in-depth analysis revealed high similarity to the YF vaccine strain 17D-213 and classified the sequence within the West Africa II genotype,clustering with the 17D vaccine strain.Conclusions and Implications for Public Health Practice:This case represented YF AEFI.The implementation of tNGS technology enables more precise and expeditious pathogen sequencing,providing critical evidence for accurate disease diagnosis and informed public health interventions.
文摘Endophthalmitis is a serious ophthalmic disease characterized by changes in the eye's posterior segment,such as hypopyon and intraocular inflammation,vitritis being a hallmark.Infection-caused endophthalmitis can lead to irreversible vision loss,accompanied by eye pain or eye distention,and in the most severe cases the removal of the eyeball.Microorganisms such as bacteria,fungi,viruses,and parasites typically account for the disease and the entry pathways of the microbial can be divided into either endogenous or exogenous approaches,according to the origin of the etiological agents.Exogenous endophthalmitis can be derived from various occasions(such as postoperative complications or trauma)while endogenous endophthalmitis results from the bloodstream which carries pathogens to the eye.This review aims to summarize the application of new technology in pathogen identification of endophthalmitis so as to prevent the disease and better guide clinical diagnosis and treatment.
基金supported by grants from projects supported by the National Natural Science Foundation of China(91959113,81972358,and 81572893)the Natural Science Foundation of Jiangsu Province(BK20180036 and BE2017733)。
文摘Previous studies have demonstrated that Chinese lung adenocarcinoma(LUAD)patients have unique genetic characteristics,however,the specific genomic features relating to the development and treatment of LUAD in the Chinese population are not fully understood.Here,we applied the ultra-deep targeted sequencing to 66 Chinese LUAD samples,accompanied by comparative analysis with 162 Caucasian LUAD in The Cancer Genome Atlas.We focused on the 68 recurrently mutated genes and results revealed that the panel-based tumor mutational burden(pTMB)is significantly higher in the Chinese LUAD(P=0.0017).Additionally,the percentage of smoking-associated C>A transversion is significantly lower in Chinese LUAD(15.5%vs.39.7%,P=5.69×10^(-27)),while C>T transition is more frequent in Chinese LUAD(35.8%vs.25.7%,P=2.67×10^(-5)),which indicated the ethnic difference in mutation types.Notably,novel driver genes(GNAS and JAK1)that are peculiar to Chinese LUAD were identified,and a more convergent distribution of mutations was observed in the Chinese cohort(P=0.012)compared with scattered mutations in Caucasian LUAD.Our results present a distinct genomic profile of Chinese LUAD compared to Caucasians LUAD and elucidate the ethnic difference in mutation distribution besides the type and rate.
