Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform th...Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform the first de novo genome assembly of M.fortis,comprehensive gene annotation analysis,and evolution analysis.Furthermore,we compare the recovery rate of schistosomes,pathological changes,and liver transcriptomes between M.fortis and mice at different time points after infection.We observe that the time and type of immune response in M.fortis are different from those in mice.M.fortis activates immune and inflammatory responses on the 10th day post infection,such as leukocyte extravasation,antibody activation,Fc-gamma receptor-mediated phagocytosis,and the interferon signaling cascade,which play important roles in preventing the development of schistosomes.In contrast,an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes.Infected mice suffer severe pathological injury and continuous decreases in cell cycle,lipid metabolism,and other functions.Our findings offer new insights into the intrinsic resistance mechanism of M.fortis against schistosome infection.The genome sequence also provides the basis for future studies of other important traits in M.fortis.展开更多
Homologous recombination deficiency(HRD)has emerged as a critical prognostic and predictive biomarker in oncology.However,current test-ing methods,especially those reliant on targeted panels,are plagued by inconsisten...Homologous recombination deficiency(HRD)has emerged as a critical prognostic and predictive biomarker in oncology.However,current test-ing methods,especially those reliant on targeted panels,are plagued by inconsistent results from the same samples.This highlights the urgent need for standardized benchmarks to evaluate HRD assay performance.In phases lla and Ilb of the Chinese HRD Harmonization Project,we de-veloped ten pairs of well-characterized DNA reference materials derived from lung,breast,and melanoma cancer cell lines and their matched normal cell lines,keeping each paired with seven cancer-to-normal mass ratios.Reference datasets for allele-specific copy number variations(AsCNVs)and HRD scores were established and validated using three sequencing methods and nine analytical pipelines.The genomic instabil-ity scores(GISs)of the reference materials ranged from 11 to 96,enabling validation across various thresholds.The AsCNV reference datasets covered a genomic span of 2340 to 2749 Mb,equivalent to 81.2%to 95.4%of the autosomes in the 37d5 reference genome.These bench-marks were subsequently utilized to assess the accuracy and reproducibility of four HRD panel assays,revealing significant variability in both ASCNV detection and HRD scores.The concordance between panel-detected GISs and reference GISs ranged from 0.81 to 0.94,with only two assays exhibiting high overall agreement with Myriad MyChoice CDx for HRD classification.This study also identified specific challenges in ASCNV detection in HRD-related regions and the profound impact of high ploidy on consistency.The established HRD reference materials and datasets providea robust toolkit forobjective evaluation of HRD testing.展开更多
To the Editor:Chronic kidney disease(CKD)is a global burden of the public health.The global prevalence of CKD exceeded 10%while the awareness was around 10%.[1]In the era of big data,improving the identification of CK...To the Editor:Chronic kidney disease(CKD)is a global burden of the public health.The global prevalence of CKD exceeded 10%while the awareness was around 10%.[1]In the era of big data,improving the identification of CKD using informatic tools is important.Computable phenotype is proven as an efficient tool to facilitate the process of patient identification using electronic health record(EHR)data.展开更多
Dear Editor,Recent studies show that induced pluripotent stem cells(iPSCs)generated through ectopic expression of transcription factors retain an epigenetic memory of their original somatic cells(Kim et al.,2010;Polo ...Dear Editor,Recent studies show that induced pluripotent stem cells(iPSCs)generated through ectopic expression of transcription factors retain an epigenetic memory of their original somatic cells(Kim et al.,2010;Polo et al.,2010)or aberrant silencing of a single imprinted gene cluster(Liu et al.,2010;Stadtfeld et al.,2010),which affects their developmental and differentiation potentials.展开更多
Inefficient nitrogen(N)utilization in agricultural production has led to many negative impacts such as excessive use of N fertilizers,redundant plant growth,greenhouse gases,long-lasting toxicity in ecosystem,and even...Inefficient nitrogen(N)utilization in agricultural production has led to many negative impacts such as excessive use of N fertilizers,redundant plant growth,greenhouse gases,long-lasting toxicity in ecosystem,and even effect on human health,indicating the importance to optimize N applications in cropping systems.Here,we present a multiseasonal study that focused on measuring phenotypic changes in wheat plants when they were responding to different N treatments under field conditions.Powered by drone-based aerial phenotyping and the AirMeasurer platform,we first quantified 6 N response-related traits as targets using plot-based morphological,spectral,and textural signals collected from 54 winter wheat varieties.Then,we developed dynamic phenotypic analysis using curve fitting to establish profile curves of the traits during the season,which enabled us to compute static phenotypes at key growth stages and dynamic phenotypes(i.e.,phenotypic changes)during N response.After that,we combine 12 yield production and N-utilization indices manually measured to produce N efficiency comprehensive scores(NECS),based on which we classified the varieties into 4 N responsiveness(i.e.,N-dependent yield increase)groups.The NECS ranking facilitated us to establish a tailored machine learning model for N responsiveness-related varietal classification just using N-response phenotypes with high accuracies.Finally,we employed the Wheat55K SNP Array to map single-nucleotide polymorphisms using N response-related static and dynamic phenotypes,helping us explore genetic components underlying N responsiveness in wheat.In summary,we believe that our work demonstrates valuable advances in N response-related plant research,which could have major implications for improving N sustainability in wheat breeding and production.展开更多
基金This work was supported by the Key Project in the National Science&Technology Pillar Program from the Ministry of Science and Technology(2015BAI09B04)the National Natural Science Foundation of China(31872256,31472188)+2 种基金the National Key Research and Development Program of China(2017YFD0501306)the Science and Technology Service Network Initiative of Chinese Academy of Sciences(KFJ-STS-QYZD-126,ZDBS-SSW-DQC-02)CAS Youth Innovation Promotion Association,and SA-SIBS Scholarship Program.
文摘Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform the first de novo genome assembly of M.fortis,comprehensive gene annotation analysis,and evolution analysis.Furthermore,we compare the recovery rate of schistosomes,pathological changes,and liver transcriptomes between M.fortis and mice at different time points after infection.We observe that the time and type of immune response in M.fortis are different from those in mice.M.fortis activates immune and inflammatory responses on the 10th day post infection,such as leukocyte extravasation,antibody activation,Fc-gamma receptor-mediated phagocytosis,and the interferon signaling cascade,which play important roles in preventing the development of schistosomes.In contrast,an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes.Infected mice suffer severe pathological injury and continuous decreases in cell cycle,lipid metabolism,and other functions.Our findings offer new insights into the intrinsic resistance mechanism of M.fortis against schistosome infection.The genome sequence also provides the basis for future studies of other important traits in M.fortis.
基金supported by the National Key R&D Program of China(Grant No.2022YFF1202203)the NIFDC Fund for Key Technology Research,China(Grant No.GJJS-2022-2-1).
文摘Homologous recombination deficiency(HRD)has emerged as a critical prognostic and predictive biomarker in oncology.However,current test-ing methods,especially those reliant on targeted panels,are plagued by inconsistent results from the same samples.This highlights the urgent need for standardized benchmarks to evaluate HRD assay performance.In phases lla and Ilb of the Chinese HRD Harmonization Project,we de-veloped ten pairs of well-characterized DNA reference materials derived from lung,breast,and melanoma cancer cell lines and their matched normal cell lines,keeping each paired with seven cancer-to-normal mass ratios.Reference datasets for allele-specific copy number variations(AsCNVs)and HRD scores were established and validated using three sequencing methods and nine analytical pipelines.The genomic instabil-ity scores(GISs)of the reference materials ranged from 11 to 96,enabling validation across various thresholds.The AsCNV reference datasets covered a genomic span of 2340 to 2749 Mb,equivalent to 81.2%to 95.4%of the autosomes in the 37d5 reference genome.These bench-marks were subsequently utilized to assess the accuracy and reproducibility of four HRD panel assays,revealing significant variability in both ASCNV detection and HRD scores.The concordance between panel-detected GISs and reference GISs ranged from 0.81 to 0.94,with only two assays exhibiting high overall agreement with Myriad MyChoice CDx for HRD classification.This study also identified specific challenges in ASCNV detection in HRD-related regions and the profound impact of high ploidy on consistency.The established HRD reference materials and datasets providea robust toolkit forobjective evaluation of HRD testing.
基金National Natural Science Foundation of China(Nos.82100741,82003529,91846101,81771938,81900665,82090021)Beijing Municipal Science and Technology Commission(Grant No.7212201)+5 种基金the University of Michigan Health System-Peking University Health Science Center Joint Institute for Translational and Clinical Research(Nos.BMU2020JI011,BMU2019JI005,BMU2018JI012)Beijing Nova Programme Interdisciplinary Cooperation Project(No.Z191100001119008)National Key R&D Program of the Ministry of Science and Technology of China(No.2019YFC2005000)the National Key Research and Development Program of China(No.2018AAA0102100)PKU-Baidu Fund(Nos.2020BD005,2019BD017)CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-046)
文摘To the Editor:Chronic kidney disease(CKD)is a global burden of the public health.The global prevalence of CKD exceeded 10%while the awareness was around 10%.[1]In the era of big data,improving the identification of CKD using informatic tools is important.Computable phenotype is proven as an efficient tool to facilitate the process of patient identification using electronic health record(EHR)data.
基金supported in part by grants from the Chinese Academy of Sciences(KSCX2-YW-R-110,KSCX2-YW-R-229,XDA01010403 to J.L.,KSCX1-YW-02,KJCX2-YW-M15 to J.W.)the Ministry of Science and Technology(2007CB947101,2009CB941101 to J.L.,2006CB503900,2010CB912102 to J.W.)+1 种基金the National Natural Science Foundation of China(30871430 to J.L.,30821065 to J.W.)the Shanghai Municipal Commission for Science and Technology(07DZ22919,08DJ1400502,09PJ1410900 to J.L.,07dz05907 to J.W.).
文摘Dear Editor,Recent studies show that induced pluripotent stem cells(iPSCs)generated through ectopic expression of transcription factors retain an epigenetic memory of their original somatic cells(Kim et al.,2010;Polo et al.,2010)or aberrant silencing of a single imprinted gene cluster(Liu et al.,2010;Stadtfeld et al.,2010),which affects their developmental and differentiation potentials.
基金supported by the National Natural Science Foundation of China(32070400 to J.Z.)The drone-based phenotyping,field experiments,yield,and N measures were also supported by the Key Project of Modern Agriculture of Jiangsu Province(BE2019383)+1 种基金J.Z.,R.J.,and G.Deakin were partially supported by the Allan&Gill Gray Philanthropies'sustainable productivity for crops improvement(G118688 to the University of Cambridge and Q-20-0370 to NIAB)J.Z.and R.J.were supported by the One CGIAR's Seed Equal Initiative(5507-CGIA-07 to J.Z.),as well as the United Kingdom Research and Innovation's(UKRI)Biotechnology and Biological Sciences Research Council's(BBSRC)International Partnership Grant(BB/X511882/1).
文摘Inefficient nitrogen(N)utilization in agricultural production has led to many negative impacts such as excessive use of N fertilizers,redundant plant growth,greenhouse gases,long-lasting toxicity in ecosystem,and even effect on human health,indicating the importance to optimize N applications in cropping systems.Here,we present a multiseasonal study that focused on measuring phenotypic changes in wheat plants when they were responding to different N treatments under field conditions.Powered by drone-based aerial phenotyping and the AirMeasurer platform,we first quantified 6 N response-related traits as targets using plot-based morphological,spectral,and textural signals collected from 54 winter wheat varieties.Then,we developed dynamic phenotypic analysis using curve fitting to establish profile curves of the traits during the season,which enabled us to compute static phenotypes at key growth stages and dynamic phenotypes(i.e.,phenotypic changes)during N response.After that,we combine 12 yield production and N-utilization indices manually measured to produce N efficiency comprehensive scores(NECS),based on which we classified the varieties into 4 N responsiveness(i.e.,N-dependent yield increase)groups.The NECS ranking facilitated us to establish a tailored machine learning model for N responsiveness-related varietal classification just using N-response phenotypes with high accuracies.Finally,we employed the Wheat55K SNP Array to map single-nucleotide polymorphisms using N response-related static and dynamic phenotypes,helping us explore genetic components underlying N responsiveness in wheat.In summary,we believe that our work demonstrates valuable advances in N response-related plant research,which could have major implications for improving N sustainability in wheat breeding and production.
