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基于表观基因组数据的乳腺癌预后基因-年龄交互作用研究

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中华流行病学杂志 2024年第7期45卷 1007-1013页

作者：周添霖薛茂杰戴智翔张汝阳陈峰南京医科大学公共卫生学院生物统计学系南京211166 南京医科大学附属常州第二人民医院信息科常州213164 南京医科大学环境与人类健康国际联合研究中心南京211166

目的基于表观基因组数据,探索乳腺癌预后基因-年龄交互作用。方法利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)多个独立乳腺癌表观基因组数据集,进行DNA甲基化的差异表达分析。采用错误发现率(FDR)法进行多重校正,保留q-FDR≤0.0... 详细信息

目的基于表观基因组数据,探索乳腺癌预后基因-年龄交互作用。方法利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)多个独立乳腺癌表观基因组数据集,进行DNA甲基化的差异表达分析。采用错误发现率(FDR)法进行多重校正,保留q-FDR≤0.05的差异表达甲基化位点。应用三阶段分析策略,采用多因素Cox比例风险回归模型检验基因-年龄交互作用。发现阶段使用TCGA-BRCA数据库筛选q-FDR≤0.05的信号。验证阶段Ⅰ使用GSE72245数据验证交互作用,标准为P≤0.05且效应方向一致。验证阶段Ⅱ使用GSE37754和GSE75067数据再次验证信号。通过结合临床指标与交互作用信号构建预后预测模型。结果三阶段分析策略鉴定出一个甲基化位点(cg16126280_(EBF1)),其与年龄存在交互作用,共同影响患者的生存时间(交互作用HR=1.0011,95%CI:1.0007~1.0015,P<0.001)。年龄分层分析显示,cg16126280_(EBF1)的高甲基化效应在乳腺癌年轻患者(HR=0.5505,95%CI:0.3838~0.7896,P=0.001)和老年患者中完全相反(HR=2.1665,95%CI:1.2852~3.6522,P=0.004)。结论DNA甲基化位点cg16126280_(EBF1)与年龄存在交互作用,以复杂的关联模式共同影响乳腺癌预后,为年龄特异性靶向药物研发提供了新的人群证据。

关键词：乳腺癌 DNA甲基化年龄交互作用

高温胁迫对玉米杂交种及其亲本自交系光合特性、保护酶活性和产量的影响

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中国生态农业学报（中英文） 2024年第9期32卷 1470-1480页

作者：徐田军吕天放张勇刘宏伟刘月娥蔡万涛张如养宋伟邢锦丰赵久然王荣焕北京市农林科学院玉米研究所/玉米DNA指纹及分子育种北京市重点实验室北京100097

研究并明确高温胁迫对玉米杂交种及其亲本自交系叶片光合性能、产量性状等的影响,以期为耐高温玉米品种选育和推广提供理论依据。以‘京农科728’‘MC812’‘先玉335’和‘郑单958’及其亲本自交系为试验材料,于花期前后(大喇叭口期—... 详细信息

研究并明确高温胁迫对玉米杂交种及其亲本自交系叶片光合性能、产量性状等的影响,以期为耐高温玉米品种选育和推广提供理论依据。以‘京农科728’‘MC812’‘先玉335’和‘郑单958’及其亲本自交系为试验材料,于花期前后(大喇叭口期—吐丝后7 d)对其进行高温胁迫(高温胁迫15 d)处理,研究高温胁迫对不同基因型玉米杂交种及其亲本自交系叶绿素相对含量、光合特性、最大光化学效率(F_(v)/F_(m))、保护酶活性、产量及其产量构成要素的影响。结果表明:1)与大田对照相比,花期前后高温胁迫下不同杂交种及其亲本自交系的叶绿素相对含量、净光合速率、气孔导度和F_(v)/F_(m)均呈降低趋势,杂交种以‘京农科728’降幅最小,亲本自交系以‘京2416’降幅最小。胞间CO_(2)浓度和蒸腾速率则均呈升高趋势,杂交种以‘京农科728’增幅最小,亲本自交系以‘京2416’增幅最小。2)花期前后高温胁迫导致玉米杂交种及其亲本自交系的穗位叶磷酸烯醇式丙酮酸羧化酶(PEPCase)、核酮糖-1,5-二磷酸羧化酶(RuBPCase)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性呈降低趋势。3)花期前后高温胁迫降低了玉米杂交种及其亲本自交系的穗行数和行粒数,进而导致产量下降,杂交种‘京农科728’‘MC812’‘先玉335’和‘郑单958’产量分别降低3.18%、5.00%、50.61%和9.50%;亲本自交系中,‘京2416’的穗行数、行粒数和产量降幅最小,而‘PH6WC’产量降幅最大。由此可见,花期前后高温胁迫下‘京农科728’‘MC812’及其父本自交‘京2416’具有较高的叶绿素相对含量、光合能力和保护酶活性,产量受高温影响较小,具有较好的耐热性。

关键词：玉米杂交种亲本自交系高温胁迫光合特性保护酶活性产量

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Trash to treasure:lactate and protein lactylation in maize root impacts response to drought

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Science China(Life Sciences) 2023年第8期66卷 1903-1914页

作者： Zi Shi Miaoyi Zhou Wei Song Ya Liu Ronghuan Wang Yuandong Wang ruyang zhang Jiuran Zhao Wen Ren Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Beijing Academy of Agriculture and Forestry SciencesBeijing 100097China

Lactate,protein lactylation(Kla),and specifically histone lactylation have recently been shown to regulate antipathogenic immune responses in ***,after we confirmed the presence and accumulation of lactate in maize roots under drought conditions,a lactylome profiling analysis revealed that Kla modifications were invariably present in maize roots,that there were obvious differences in the lactylomes of drought-sensitive(B73)***-tolerant(Jing2416)lines,and that growing Jing2416 under drought conditions caused significant decreases in the lactylation of multiple enzymes responsible for fatty acid *** by findings of histone-Kla based epigenetic regulation of immune functions in animals,we initially discovered 37 Kla sites on 16 histones in the maize genome,and again detected obvious differential histone Klamediated trends between two lines by Ch ***,only 2.7%of genes with differential histone Kla peaks detected during drought stress were commonly present in both lines,a finding demonstrating that abiotic stress triggers distinct epigenetic activities in diverse germplasm while also strongly supporting that a histone Kla layer of regulation is associated with physiological responses to drought ***,exogenous application of spermidine improved the drought tolerance of B73and substantially altered the levels of lactate,protein lactylation,and histone Kla ***,beyond extending the known domain of Kla-based biochemical and epigenetic regulation from animal immunity to plant stress physiology,our study suggests the physiological,biochemical,and genetic function of“the best-known metabolic waste”,lactate.

关键词： lactate lactylome drought spermidine maize

不同玉米杂交种及其亲本自交系耐热性的差异比较

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中国农业科学 2024年第2期57卷 403-415页

作者：徐田军吕天放李自豪张勇刘宏伟刘月娥蔡万涛张如养宋伟邢锦丰赵久然王荣焕北京市农林科学院玉米研究所/玉米DNA指纹及分子育种北京市重点实验室

【目的】近年来，我国黄淮海夏玉米区高温热害不利天气频发重发，已成为威胁玉米生产的重要不利因素。研究并明确高温胁迫对不同基因型玉米品种雌雄穗及产量的影响，为耐高温玉米品种培育和选择提供参考。【方法】以郑单958（郑58×昌7-... 详细信息

【目的】近年来，我国黄淮海夏玉米区高温热害不利天气频发重发，已成为威胁玉米生产的重要不利因素。研究并明确高温胁迫对不同基因型玉米品种雌雄穗及产量的影响，为耐高温玉米品种培育和选择提供参考。【方法】以郑单958（郑58×昌7-2）、先玉335(PH6WC×PH4CV)、京农科728（京MC01×京2416）和MC812（京B547×京2416）及其亲本自交系为供试材料，花期前后（大喇叭口期-吐丝后7 d）进行高温胁迫处理，研究高温胁迫对不同基因型玉米杂交种及其亲本自交系雌雄穗生长发育、散粉吐丝间隔（ASI）、花粉活性、产量及其构成要素的影响。【结果】（1）花期前后高温胁迫导致参试玉米品种及其亲本自交系的穗粒数减少，进而产量降低，且不同品种和自交系对高温胁迫的响应存在显著差异。与对照相比，高温胁迫下，郑单958、先玉335、京农科728和MC812的穗粒数降幅分别为22.28%、46.79%、6.13%和8.11%，产量降幅分别为9.50%、50.61%、3.18%和5.00%，其中，京农科728和MC812减产不显著，而郑单958和先玉335显著减产；亲本自交系中，京2416的穗行数、行粒数和产量降幅最小且不显著，而PH6WC均显著降低且降幅最大。（2）高温胁迫下，参试品种及其亲本自交系的雄穗分支总数、雄穗长度、总散粉量和花粉活性降低，散粉持续期缩短，ASI延长。与对照相比，高温胁迫下，ASI延长1.6 d。雄穗长度降幅表现为郑单958>先玉335>MC812>京农科728。郑单958雄穗长度降幅最大，但雄穗分支数多，花粉量最大；先玉335雄穗分支少，雄穗长度降幅大，花粉量最少且活性最低；京2416总散粉量大且花粉活力强，降幅最小（仅为4.50%和3.98%）。【结论】花期前后高温胁迫对参试玉米品种的籽粒产量和花粉活性等影响较大，京农科728和MC812的产量和花粉活性降幅显著低于先玉335和郑单958，耐热性较好。通过比较参试玉米杂交种亲本自交系的耐热性，父本自交系的耐热性要好于母本自交系。其中，京2416的雄穗分支和长度降幅小，花粉量大，花粉活性高，且花丝茸毛多，捕获花粉能力强，单穗产量高，ASI小，耐热性最好。因此，在耐高温玉米品种选育过程中，要重视和加大对耐热种质（如京2416等）的利用与改良创新，组配选育耐高温玉米新品种。

关键词：高温玉米亲本自交系耐热性

Global COVID-19 Pandemic Waves: Limited Lessons Learned Worldwide over the Past Year

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Engineering 2022年第6期8卷 91-98页

作者： Yongyue Wei Jinxing Guan Xiao Ning Yuelin Li Liangmin Wei Sipeng Shen ruyang zhang Yang Zhao Hongbing Shen Feng Chen Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human Health&Center for Global Health Nanjing Medical UniversityNanjing 211166China Department of Biomedical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Institute for Social and Economic Research and Policy Columbia UniversityNew YorkNY 10027USA

The occurrence of coronavirus disease 2019(COVID-19)was followed by a small burst of cases around the world;afterward,due to a series of emergency non-pharmaceutical interventions(NPIs),the increas-ing number of confirmed cases slowed down in many ***,the lifting of control measures by the government and the public’s loosening of precautionary behaviors led to a sudden increase in cases,arousing deep concern across the *** deep concern across the *** study evaluates the situation of the COVID-19 pandemic in countries and territories worldwide from January 2020 to February *** to the time-varying reproduction number(R(t))of each country or territory,the results show that almost half of the countries and territories in the world have never controlled the *** the countries and territories that had once contained the occurrence,nearly half failed to maintain their prevention and control,causing the COVID-19 pandemic to rebound across the world—resulting in even higher waves in half of the rebounding countries or *** work also proposes and uses a time-varying country-level transmission risk score(CTRS),which takes into account both R(t)and daily new cases,to demonstrate country-level or territory-level transmission potential and ***-varying hierarchical clustering of time-varying CTRS values was used to successfully reveal the countries and territories that contributed to the recent aggravation of the global pandemic in the last quarter of 2020 and the beginning of 2021,and to identify countries and territories with an increasing risk of COVID-19 transmission in the near ***,a regression analysis indicated that the introduction and relaxation of NPIs,including workplace closure policies and stay-at-home requirements,appear to be associated with recent global transmission *** conclu-sion,a systematic evaluation of the global COVID-19 pandemic over the past year indicates that

关键词： COVID-19 Global pandemic Prevention and control effect

Statistical analysis for genome-wide association study

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The Journal of Biomedical Research 2015年第4期29卷 285-297页

作者： Ping Zeng Yang Zhao Cheng Qian Liwei zhang ruyang zhang Jianwei Gou Jin Liu Liya Liu Feng Chen Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical University Department of Epidemiology and Biostatistics School of Public HealthXuzhou Medical College

In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic insights into understanding pathogenesis of diseases. In this paper, we present an overview of widely used approaches and strategies for analysis of GWAS, offered a general consideration to deal with GWAS data. The issues regarding data quality control, population structure, association analysis, multiple comparison and visual presentation of GWAS results are discussed; other advanced topics including the issue of missing heritability, meta-analysis, setbased association analysis, copy number variation analysis and GWAS cohort analysis are also briefly introduced.

关键词： genome-wide association study quality control multiple comparison population structure genetic model statistical model missing heritability meta-analysis copy number variation

Transmission dynamics model and the coronavirus disease 2019 epidemic:applications and challenges

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Medical Review 2022年第1期2卷 89-109页

作者： Jinxing Guan Yang Zhao Yongyue Wei Sipeng Shen Dongfang You ruyang zhang Theis Lange Feng Chen Departments of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjing 211166JiangsuChina China International Cooperation Center for Environment and Human Health Center for Global HealthNanjing Medical UniversityNanjing 211166JiangsuChina Center of Biomedical BigData Nanjing Medical UniversityNanjing 211166JiangsuChina Department of Public Health University of CopenhagenCopenhagenDenmark

Since late 2019,the beginning of coronavirus disease 2019(COVID-19)pandemic,transmission dynamics models have achieved great development and were widely used in predicting and ***,we provided an introduction to the history of disease transmission,summarized transmission dynamics models into three main types:compartment extension,parameter extension and population-stratified extension models,highlight the key contribution of transmission dynamics models in COVID-19 pandemic:estimating epidemiological parameters,predicting the future trend,evaluating the effectiveness of control measures and exploring different possibilities/***,we pointed out the limitations and challenges lie ahead of transmission dynamics models.

关键词： compartment model coronavirus disease 2019 novel coronavirus pneumonia SEIR SIR transmission dynamics model.

Identification of a locus associated with genic male sterility in maize via EMS mutagenesis and bulked-segregant RNA-seq

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The Crop Journal 2021年第6期9卷 1263-1269页

作者： Zi Shi Wen Ren Yanxin Zhao Xiaqing Wang ruyang zhang Aiguo Su Shuai Wang Chunhui Li Jiarong Wang Shuaishuai Wang Yunxia zhang Yulong Ji Wei Song Jiuran Zhao Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Maize Research CenterBeijing Academy of Agriculture&Forestry SciencesBeijing 100097China

Genic male sterility(GMS) is one of the most important resources for exploiting heterosis in crop breeding, so that identifying genomic loci regulating GMS is desirable. However, many regulatory genes controlling GMS have not yet been characterized in maize, owing partly to a lack of genetic materials. We generated a recessive male-sterile maize mutant in the Jing 724 genetic background via ethyl methanesulfonate treatment, and found the male sterility to be due to a single gene mutation. Bulk-segregant RNA sequencing of three replicates indicated that one genomic region located at the end of chromosome 4 was associated with the observed mutant phenotype. Among genes with nonsynonymous mutations,Zm00001 d053895(bHLH51) showed abolished expression in the sterile bulks and was annotated as a bHLH transcription factor orthologous to Arabidopsis AMS, suggesting an association with the male sterility of the mutant. Kompetitive Allele-Specific PCR assays further validated the exclusive correlation of male sterility with the single C-to-T mutation in the fifth exon. The new maize mutant and the potential SNP locus provide novel genetic material for investigating the molecular mechanism underlying tapetal development and may facilitate the improvement of hybrid production systems.

关键词： Genic male sterility EMS-induced mutant BSR-seq bHLH51 Maize

ORF355 confers enhanced salinity stress adaptability to S-type cytoplasmic male sterility maize by modulating the mitochondrial metabolic homeostasis

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Journal of Integrative Plant Biology 2023年第3期65卷 656-673页

作者： Senlin Xiao Wei Song Jinfeng Xing Aiguo Su Yanxin Zhao Chunhui Li Zi Shi Zhiyong Li Shuai Wang ruyang zhang Yuanrong Pei Huabang Chen Jiuran Zhao Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Maize Research InstituteBeijing Academy of Agriculture and Forestry SciencesBeijing 100097China State Key Laboratory of Plant Cell and Chromosome Engineering Innovative Academy of Seed DesignInstitute of Genetics and Developmental Biologythe Chinese Academy of SciencesBeijing 100101China

Moderate stimuli in mitochondria improve wideranging stress adaptability in animals, but whether mitochondria play similar roles in plants is largely unknown. Here, we report the enhanced stress adaptability of S-type cytoplasmic male sterility(CMS-S) maize and its association with mild expression of sterilizing gene ORF355. A CMS-S maize line exhibited superior growth potential and higher yield than those of the near-isogenic N-type line in saline fields. Moderate expression of ORF355 induced the accumulation of reactive oxygen species and activated the cellular antioxidative defense system. This adaptive response was mediated by elevation of the nicotinamide adenine dinucleotide concentration and associated metabolic homeostasis. Metabolome analysis revealed broad metabolic changes in CMS-S lines, even in the absence of salinity stress. Metabolic products associated with amino acid metabolism and galactose metabolism were substantially changed, which underpinned the alteration of the antioxidative defense system in CMS-S plants. The results reveal the ORF355-mediated superior stress adaptability in CMS-S maize and might provide an important route to developing salt-tolerant maize varieties.

关键词： cytoplasmic male sterility metabolic homeostasis mitochondria salinity stress adaptability Zea mays L.