When detecting deletions in complex human genomes,split-read approaches using short reads generated with next-generation sequencing still face the challenge that either false discovery rate is high,or sensitivity is l...When detecting deletions in complex human genomes,split-read approaches using short reads generated with next-generation sequencing still face the challenge that either false discovery rate is high,or sensitivity is low.To address the problem,an integrated strategy is proposed.It organically combines the fundamental theories of the three mainstream methods(read-pair approaches,split-read technologies and read-depth analysis) with modern machine learning algorithms,using the recipe of feature extraction as a bridge.Compared with the state-of-art split-read methods for deletion detection in both low and high sequence coverage,the machine-learning-aided strategy shows great ability in intelligently balancing sensitivity and false discovery rate and getting a both more sensitive and more precise call set at single-base-pair resolution.Thus,users do not need to rely on former experience to make an unnecessary trade-off beforehand and adjust parameters over and over again any more.It should be noted that modern machine learning models can play an important role in the field of structural variation prediction.展开更多
【Background】The application of beneficial-microbial seed soaking prior to sowing represents a novel technology that has not been employed in Lanzhou lily cultivation.We conducted an experiment to explore the impact ...【Background】The application of beneficial-microbial seed soaking prior to sowing represents a novel technology that has not been employed in Lanzhou lily cultivation.We conducted an experiment to explore the impact of this soaking method on the fungal and bacterial community structures using next-generation sequencing technology(NGS).【Methods】Lily bulbs were soaked in a seed treating agent containing beneficial microbes(SP treatment)for 4 hours.Subsequently,they were planted in soil in July and sampled in September to assess plant growth,rhizosphere soil physicochemical properties,and microorganism community structures.In addition,we employed the software PICRUSt and FUNGuild to predict bacterial pathways and fungal functions.【Results】Under SP treatment,there were significant alterations in fungi and bacteria community structures,accompanied by improved soil nutrient status.Notably,the relative abundance of dominant microorganism groups,such as the fungi Basidiomycota,Pseudeurotium,Cladophialophora,Microascus,and Dactylonectria,as well as the bacteria Proteobacteria,Chloroflexi,Ochrobactrium,Lysobacter,and RB41,underwent notable changes.Microorganism function prediction results indicated a reduction in pathotrophic fungi(including plant pathogens)and an increase in endophytic and saprotrophic fungi under SP treatment.Among the top 20 metabolism pathways,80%were upregulated in SP treatment compared to the CK.【Conclusions】Seed soaking with beneficial microbial strain promotes the growth of Lanzhou lily bulbs.The beneficial microorganisms play a crucial role in regulating soil microbial structures,enhancing the accumulation of endophytic fungi,reducing the abundance of pathogens,and improving soil functions.Furthermore,specific microbial groups are found to be involved in maintaining soil health.展开更多
在全球气候变化和高强度人类活动的共同影响下,许多流域天然水循环过程受到破坏。径流序列呈现明显的非平稳特性,给水资源规划、管理、预测和调控带来一定的挑战。揭示径流序列的非平稳特性可以有效应对全球气候变化下的复杂水问题,对...在全球气候变化和高强度人类活动的共同影响下,许多流域天然水循环过程受到破坏。径流序列呈现明显的非平稳特性,给水资源规划、管理、预测和调控带来一定的挑战。揭示径流序列的非平稳特性可以有效应对全球气候变化下的复杂水问题,对降低水文分析难度和提高径流预测精度具有十分重要的意义。研究以汾河上游兰村站为研究对象,分析该站1958-2016年年径流和月径流序列是否平稳。首先从随机水文学角度,采用Mann-Kendall检验法和小波分析法识别径流序列的趋势、突变和周期特征。在此基础上,从统计水文学角度引入Ng-Perron单位根检验方法。通过Mann-Kendall趋势检验和散点图法选择合适的检验方程,对径流序列进行广义最小二乘法(Generalized Least Squares,GLS)退势,并利用修正的信息准则(Modified information criterion,MIC)计算最优时间滞后阶数,判别径流序列是否具有非平稳性。结果显示,径流序列存在趋势、突变和周期成分,为非平稳径流序列。同时Ng-Perron单位根检验表明,该站年、月径流序列在1%显著性水平上具有非平稳特性。相较传统单位根检验方法,Ng-Perron单位根检验采用更为稳健的修正检验统计量,显著调整小样本情况下水平扭曲的现象,具有更好检验水平和功效,因而可以得到更合理的检验结果。研究成果为径流序列非平稳性检验理论的进一步改进及径流预测模型发展与应用提供参考。展开更多
The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South Univers...The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).展开更多
目的评价免疫层析法NG-Test CARBA 5筛查碳青霉烯酶分型KPC、NDM、VIM、IMP和OXA48筛查价值。方法计算机检索PubMed(2008.01-2020.12)数据库、ISI Web of Knowledge(2008.01-2020.12)数据库、中文期刊全文数据库(2008.01-2020.12)、中...目的评价免疫层析法NG-Test CARBA 5筛查碳青霉烯酶分型KPC、NDM、VIM、IMP和OXA48筛查价值。方法计算机检索PubMed(2008.01-2020.12)数据库、ISI Web of Knowledge(2008.01-2020.12)数据库、中文期刊全文数据库(2008.01-2020.12)、中文科技期刊数据库(2008.01-2020.12)、万方数据库(2008.01-2020.12),利用手工检索,2名评价员严格依据纳入排除标准收集NGTest CARBA 5筛查碳青霉烯酶分型的试验。依据QUADAS质量评价标准评价纳入研究的质量,后用Meta-Disc软件对数据进行Meta分析。结果最后纳入8个研究文献,一共纳入1634例菌株。Meta分析结果显示:NG-Test CARBA 5筛查碳青霉烯酶,包含KPC、NDM、VIM、IMP、OXA48合并敏感性和特异性分别为99.7%和100%、98.6%和100%、97.6%和100%、92.6%和100%、100%和99.8%。结论NG-Test CARBA 5筛查KPC、NDM、VIM、IMP、OXA485种碳青霉烯酶具有高敏感性和特异性,适用于临床。展开更多
目的探讨低级别嗜酸细胞性肾肿瘤(low-grade oncocytic tumor of kidney,LOT)的临床病理特征、免疫表型、分子改变及鉴别诊断,同时寻找敏感的客观指标辅助诊断。方法收集14例LOT的临床病理资料,行光镜观察、免疫组化染色等,其中8例送检...目的探讨低级别嗜酸细胞性肾肿瘤(low-grade oncocytic tumor of kidney,LOT)的临床病理特征、免疫表型、分子改变及鉴别诊断,同时寻找敏感的客观指标辅助诊断。方法收集14例LOT的临床病理资料,行光镜观察、免疫组化染色等,其中8例送检了高通量靶向基因突变检测。结果14例中男性4例,女性10例,年龄46~88岁,中位年龄57.5岁,平均61.1岁,平均随访6~90个月,1例患者肿瘤复发,其余无瘤生存;镜下肿瘤以实性片状、小巢状结构为主,常兼有大片出血与疏松水肿区域;胞质嗜酸性、细颗粒状,细胞核圆,核仁不明显,常见核周空晕,不易见核皱缩、核多形。免疫表型:LOT免疫表型一致性较好,所有病例均呈现经典的CK7+/CD117-表型(14/14,100%);CD10、CK20、vimentin均呈阴性(0/14,0);Ki67增殖指数1%~3%;此外,新提出的鉴别抗体GPNMB(14/14,100%)弥漫强阳性;GATA3(14/14,100%)至少部分区域中等程度核阳性。高通量测序:8例送检NGS测序,均有MTOR或TSC1基因致病性/可能致病性突变(7例有MTOR基因突变,1例有TSC1基因突变)。结论LOT是一种低级别嗜酸性肿瘤,具有可辨识的形态学特点和免疫表型、分子特征,偏向惰性生物学行为,是一种独立的嗜酸性肿瘤亚型。展开更多
全基因组关联研究(Genome-wide association study,GWAS)是人类复杂疾病研究的重要组成部分之一,在群体水平检测全基因组范围的遗传变异与可观测性状间的遗传关联。传统的GWAS是以芯片(Array)技术获得高密度的遗传变异,尽管硕果累累,但...全基因组关联研究(Genome-wide association study,GWAS)是人类复杂疾病研究的重要组成部分之一,在群体水平检测全基因组范围的遗传变异与可观测性状间的遗传关联。传统的GWAS是以芯片(Array)技术获得高密度的遗传变异,尽管硕果累累,但也存在不少问题。如:所谓的"缺失的遗传力",即利用关联分析检测达到全基因组水平显著的遗传变异位点只能解释小部分遗传力;在某些性状上不同研究的结果一致性较弱;显著关联的遗传变异位点的功能较难解释等。高通量测序技术,也称第二代测序(Next-generation sequencing,NGS)技术,可以快速、准确地产出高通量的变异位点数据,为解决以上问题提供了可行的方案。基于NGS技术的GWAS方法(NGS-GWAS)可在一定程度上弥补传统GWAS的不足。文章对NGS-GWAS策略和方法进行了系统性调研,提出了目前较为可行的NGS-GWAS的实施策略和方法,并对NGS-GWAS如何应用于个体化医疗(Personalized medicine,PM)进行了展望。展开更多
基金Project(61472026)supported by the National Natural Science Foundation of ChinaProject(2014J410081)supported by Guangzhou Scientific Research Program,China
文摘When detecting deletions in complex human genomes,split-read approaches using short reads generated with next-generation sequencing still face the challenge that either false discovery rate is high,or sensitivity is low.To address the problem,an integrated strategy is proposed.It organically combines the fundamental theories of the three mainstream methods(read-pair approaches,split-read technologies and read-depth analysis) with modern machine learning algorithms,using the recipe of feature extraction as a bridge.Compared with the state-of-art split-read methods for deletion detection in both low and high sequence coverage,the machine-learning-aided strategy shows great ability in intelligently balancing sensitivity and false discovery rate and getting a both more sensitive and more precise call set at single-base-pair resolution.Thus,users do not need to rely on former experience to make an unnecessary trade-off beforehand and adjust parameters over and over again any more.It should be noted that modern machine learning models can play an important role in the field of structural variation prediction.
文摘【Background】The application of beneficial-microbial seed soaking prior to sowing represents a novel technology that has not been employed in Lanzhou lily cultivation.We conducted an experiment to explore the impact of this soaking method on the fungal and bacterial community structures using next-generation sequencing technology(NGS).【Methods】Lily bulbs were soaked in a seed treating agent containing beneficial microbes(SP treatment)for 4 hours.Subsequently,they were planted in soil in July and sampled in September to assess plant growth,rhizosphere soil physicochemical properties,and microorganism community structures.In addition,we employed the software PICRUSt and FUNGuild to predict bacterial pathways and fungal functions.【Results】Under SP treatment,there were significant alterations in fungi and bacteria community structures,accompanied by improved soil nutrient status.Notably,the relative abundance of dominant microorganism groups,such as the fungi Basidiomycota,Pseudeurotium,Cladophialophora,Microascus,and Dactylonectria,as well as the bacteria Proteobacteria,Chloroflexi,Ochrobactrium,Lysobacter,and RB41,underwent notable changes.Microorganism function prediction results indicated a reduction in pathotrophic fungi(including plant pathogens)and an increase in endophytic and saprotrophic fungi under SP treatment.Among the top 20 metabolism pathways,80%were upregulated in SP treatment compared to the CK.【Conclusions】Seed soaking with beneficial microbial strain promotes the growth of Lanzhou lily bulbs.The beneficial microorganisms play a crucial role in regulating soil microbial structures,enhancing the accumulation of endophytic fungi,reducing the abundance of pathogens,and improving soil functions.Furthermore,specific microbial groups are found to be involved in maintaining soil health.
文摘在全球气候变化和高强度人类活动的共同影响下,许多流域天然水循环过程受到破坏。径流序列呈现明显的非平稳特性,给水资源规划、管理、预测和调控带来一定的挑战。揭示径流序列的非平稳特性可以有效应对全球气候变化下的复杂水问题,对降低水文分析难度和提高径流预测精度具有十分重要的意义。研究以汾河上游兰村站为研究对象,分析该站1958-2016年年径流和月径流序列是否平稳。首先从随机水文学角度,采用Mann-Kendall检验法和小波分析法识别径流序列的趋势、突变和周期特征。在此基础上,从统计水文学角度引入Ng-Perron单位根检验方法。通过Mann-Kendall趋势检验和散点图法选择合适的检验方程,对径流序列进行广义最小二乘法(Generalized Least Squares,GLS)退势,并利用修正的信息准则(Modified information criterion,MIC)计算最优时间滞后阶数,判别径流序列是否具有非平稳性。结果显示,径流序列存在趋势、突变和周期成分,为非平稳径流序列。同时Ng-Perron单位根检验表明,该站年、月径流序列在1%显著性水平上具有非平稳特性。相较传统单位根检验方法,Ng-Perron单位根检验采用更为稳健的修正检验统计量,显著调整小样本情况下水平扭曲的现象,具有更好检验水平和功效,因而可以得到更合理的检验结果。研究成果为径流序列非平稳性检验理论的进一步改进及径流预测模型发展与应用提供参考。
基金supported by the National Natural Science Foundation(81900070)the Natural Science Foundation of Hunan Province(2020JJ5813)China。
文摘The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).
文摘目的探讨低级别嗜酸细胞性肾肿瘤(low-grade oncocytic tumor of kidney,LOT)的临床病理特征、免疫表型、分子改变及鉴别诊断,同时寻找敏感的客观指标辅助诊断。方法收集14例LOT的临床病理资料,行光镜观察、免疫组化染色等,其中8例送检了高通量靶向基因突变检测。结果14例中男性4例,女性10例,年龄46~88岁,中位年龄57.5岁,平均61.1岁,平均随访6~90个月,1例患者肿瘤复发,其余无瘤生存;镜下肿瘤以实性片状、小巢状结构为主,常兼有大片出血与疏松水肿区域;胞质嗜酸性、细颗粒状,细胞核圆,核仁不明显,常见核周空晕,不易见核皱缩、核多形。免疫表型:LOT免疫表型一致性较好,所有病例均呈现经典的CK7+/CD117-表型(14/14,100%);CD10、CK20、vimentin均呈阴性(0/14,0);Ki67增殖指数1%~3%;此外,新提出的鉴别抗体GPNMB(14/14,100%)弥漫强阳性;GATA3(14/14,100%)至少部分区域中等程度核阳性。高通量测序:8例送检NGS测序,均有MTOR或TSC1基因致病性/可能致病性突变(7例有MTOR基因突变,1例有TSC1基因突变)。结论LOT是一种低级别嗜酸性肿瘤,具有可辨识的形态学特点和免疫表型、分子特征,偏向惰性生物学行为,是一种独立的嗜酸性肿瘤亚型。
文摘全基因组关联研究(Genome-wide association study,GWAS)是人类复杂疾病研究的重要组成部分之一,在群体水平检测全基因组范围的遗传变异与可观测性状间的遗传关联。传统的GWAS是以芯片(Array)技术获得高密度的遗传变异,尽管硕果累累,但也存在不少问题。如:所谓的"缺失的遗传力",即利用关联分析检测达到全基因组水平显著的遗传变异位点只能解释小部分遗传力;在某些性状上不同研究的结果一致性较弱;显著关联的遗传变异位点的功能较难解释等。高通量测序技术,也称第二代测序(Next-generation sequencing,NGS)技术,可以快速、准确地产出高通量的变异位点数据,为解决以上问题提供了可行的方案。基于NGS技术的GWAS方法(NGS-GWAS)可在一定程度上弥补传统GWAS的不足。文章对NGS-GWAS策略和方法进行了系统性调研,提出了目前较为可行的NGS-GWAS的实施策略和方法,并对NGS-GWAS如何应用于个体化医疗(Personalized medicine,PM)进行了展望。
