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Molecular patterns of avian influenza A viruses

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Chinese Science Bulletin 2008年第13期53卷 2002-2007页

作者： kou zheng LEI FuMin WANG ShengYue ZHOU YanHong LI TianXian Hubei Bioinformatics and Molecular Imaging Key Laboratory Department of Systems Biology Huazhong University of Science and Technology Wuhan 430074 China State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China Institute of Zoology Chinese Academy of Sciences Beijing 100080 China Chinese National Human Genome Center Chinese Academy of Sciences Shanghai 201203 China

Avian influenza A viruses could get across the species barrier and be fatal to humans. Highly patho-genic avian influenza H5N1 virus was an example. The mechanism of interspecies transmission is not clear as yet. In this research,the protein sequences of 237 influenza A viruses with different subtypes were transformed into pseudo-signals. The energy features were extracted by the method of wavelet packet decomposition and used for virus classification by the method of hierarchical clustering. The clustering results showed that five patterns existed in avian influenza A viruses,which associated with the phenotype of interspecies transmission,and that avian viruses with patterns C and E could across species barrier and those with patterns A,B and D might not have the abilities. The results could be used to construct an early warning system to predict the transmissibility of avian influenza A viruses to humans.

关键词：禽流感病毒 H5N1 子波分解聚类种间传输

The limited number of available nucleotide and protein sequence data from the recent H7N9 cases in China impeded investigation and characterization of the outbreak

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Virologica Sinica 2014年第2期29卷 126-127页

作者： Haizhou Liu Na Han Wei Fang James Adams kou zheng Tianxian Li Zhihong Hu Simon Rayner Key Laboratory of Agricultural and Environmental Microbiology and State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences

Dear Editor,Nucleotide and protein sequences of isolates collectedfrom infected populations can be useful for determiningthe threats,such as host adaptation,which are associatedwith the emergence of new lineages.March 2013 saw thefirst reports of a new H7N9 lineage in Shanghai,Chinathat saw a gradual increase in the number of cases;but,by 17th May 2013,four Chinese provinces had

关键词：蛋白质序列序列数据核苷酸中国病例鉴定爆发上市

Molecular characterization of H3N2 and H4N6 subtypes avian influenza viruses isolated from mallards in Poyang Lake,China in 2010

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Chinese Science Bulletin 2012年第27期57卷 3586-3594页

作者： ZHU Na ZHAO JiuRu LI YongDong DING ChangQing XIA Han TANG Shuang ZHANG Zhong YU JingFeng CHEN Jing FAN ZhaoJun kou zheng LI TianXian State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of SciencesWuhan 430071China Ningbo Municipal Center for Disease Control and Prevention Ningbo 315010China College of Biology Beijing Forestry University Beijing 100083China

Poyang Lake is the largest inland freshwater lake in China and contains many species of wild birds and waterfowls.We conducted a survey of avian influenza viruses in nine semi-artificial waterfowl farms in Poyang Lake during January to March of 2010.Out of 1036 cloacal swabs collected,three H3N2 and one H4N6 influenza viruses were isolated from healthy mallards.All the isolates were genetically and phylogenetically characterized.The analysis of putative HA cleavage sites showed that all the four isolates possessed the molecular characteristics(QTRGL for H3N2 viruses,PEKASR for H4N6 virus) of lowly pathogenic avian influenza(LPAI) virus.The phylogenetic analysis of the viral genomes showed that all four virus isolates clustered in the Eurasian clade of influenza viruses.The M gene of the viruses possessed the highest homology with highly pathogenic H5N1 influenza viruses.In addition,co-infection of H3N2 and H4N6 in the same farm was observed.And interestingly,we isolated two subtypes viruses(H3N2 and H4N6) and their progeny virus(H3N2) with evidence of genome reassortment from the same farm,in which the PB1 and PB2 gene segments of H4N6 replaced those of the H3N2 strain.The results of animal infection experiments showed that all the four isolated viruses were lowly pathogenic to chickens and not pathogenic to mice,which was consistent with the results of genetic analysis.

关键词：禽流感病毒病毒分离分子特征鄱阳湖野鸭亚型中国系统发育分析

米托蒽醌甲磺酸盐预处理脂肪间充质干细胞对犬糖尿病的治疗效果评价

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畜牧兽医学报 2024年第3期55卷 1328-1344页

作者：谭宁李巴仑韩苗李琛琛景远翔寇正李娜彭莎赵献军华进联西北农林科技大学动物医学院陕西省干细胞工程技术研究中心杨凌712100 百欧派(天津)生物技术有限公司天津300350

本研究在高脂饮食(high-fat diet, HFD)饲喂和链脲佐菌素(streptozotin, STZ)注射的联合作用下成功建立小鼠及犬糖尿病模型,旨在探究米托蒽醌甲磺酸盐(mitoquionl mesylate, MitoQ)预处理脂肪间充质干细胞(adipose-derived mesenchymal stem cells, ADMSCs)对糖尿病动物模型治疗效果的提升作用及机制。取正常培养状态的ADMSCs及添加1μmol·L^(-1)MitoQ处理的ADMSCs,对MitoQ处理的细胞形态变化、生长、增殖、迁移及抗氧化能力等进行检测。选取48只8周龄的昆明(KM)雄性小鼠和12只中华田园犬,随机分为正常对照组(NC组)、糖尿病模型组(Diabetes组)、ADMSCs单独治疗组(ADMSCs组)和MitoQ预处理ADMSCs联合治疗组(MitoQ-ADMSCs组)。常规方法制作小鼠及犬糖尿病模型,对模型小鼠和犬分别进行ADMSCs和MitoQ-ADMSCs细胞静脉移植治疗,细胞数为2×10^(6)·只^(-1)(小鼠)和1×10^(7)·只^(-1)(犬),每周1次,连续3周。持续监测临床指标变化,治疗结束后1周收样,血清学、组织学、氧化应激及犬血清代谢组学分析。结果表明,MitoQ预处理ADMSCs不会影响其细胞形态,但能促进其生长、增殖及迁移能力,同时增强其抗氧化能力;ADMSCs和MitoQ-ADMSCs移植治疗后,发现MitoQ显著促进ADMSCs降低血糖的能力,且提高胰岛β细胞功能和机体血糖调节能力;ADMSCs经MitoQ预处理后有效减轻糖尿病伴发的肝代谢功能障碍和血脂代谢异常;ADMSCs可以减轻胰腺和肝组织损伤,促进胰岛素分泌,减轻肝糖原合成障碍和纤维化水平,而MitoQ处理能够显著改善ADMSCs治疗效果;MitoQ预处理ADMSCs能够有效提升机体的抗氧化能力,减轻氧化损伤,进而增强治疗效果;MitoQ预处理ADMSCs可以显著促进机体内与抗氧化相关的代谢物表达上调。结果揭示,MitoQ能够通过提高ADMSCs的抗氧化能力、加速组织损伤修复,从而更好地治疗小鼠及犬糖尿病。

关键词：米托蒽醌甲磺酸盐脂肪间充质干细胞犬糖尿病

卡瑞利珠单抗联合白蛋白紫杉醇+奈达铂/顺铂治疗老年晚期食管癌的疗效及安全性研究

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海南医学 2024年第3期35卷 310-313页

作者：王亚楠李文玉赵红珂寇卫政新乡医学院第一附属医院肿瘤科河南新乡453100 新乡医学院第一附属医院核磁共振科河南新乡453100

目的探讨卡瑞利珠单抗联合白蛋白紫杉醇+奈达铂/顺铂治疗老年晚期食管癌的疗效及安全性。方法选择2019年1月至2022年1月新乡医学院第一附属医院收治的90例食管癌患者作为研究对象,根据随机数表法将患者分为观察组和对照组,每组45例。对... 详细信息

目的探讨卡瑞利珠单抗联合白蛋白紫杉醇+奈达铂/顺铂治疗老年晚期食管癌的疗效及安全性。方法选择2019年1月至2022年1月新乡医学院第一附属医院收治的90例食管癌患者作为研究对象,根据随机数表法将患者分为观察组和对照组,每组45例。对照组患者给予白蛋白紫杉醇+奈达铂/顺铂治疗,观察组患者在对照组基础上联合卡瑞利珠单抗治疗,每21 d为一个治疗周期,所有患者均连续治疗4个周期。比较两组患者的治疗效果和化疗前后的肿瘤标志物指标[糖类抗原125(CA125)、糖类抗原199(CA199)、癌胚抗原(CEA)];随访1年统计两组患者的生存率,并记录两组患者治疗期间的不良反应情况。结果观察组患者的客观缓解率为66.67%,明显高于对照组的40.00%,差异有统计学意义(P0.05),化疗后,两组患者的CA125、CA199、CEA水平均明显降低,且观察组分别为(43.29±4.10)U/mL、(49.18±3.72)U/mL、(19.28±2.19)U/mL,明显低于对照组的(48.29±5.41)U/mL、(53.10±3.99)U/mL、(24.29±2.90)U/mL,差异均有统计学意义(P0.05)。结论卡瑞利珠单抗联合白蛋白紫杉醇+奈达铂/顺铂治疗老年晚期食管癌的效果更显著,可降低患者血清肿瘤标志物水平,提高患者1年生存率,安全性良好,可在临床推广应用。

关键词：老年食管癌卡瑞利珠单抗白蛋白紫杉醇奈达铂/顺铂疗效安全性

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基于深度学习的禽流感病毒溢出风险预测研究

广州大学学报（自然科学版） 2024年第2期23卷 48-56页

作者：刘耀华范馨月徐雪健王娜寇铮强小利广州大学计算科技研究院广东广州510006 广州大学计算机科学与网络工程学院广东广州510006

禽流感病毒基因组由8个长短不一的基因节段组成,全长约为14~16 kb。由于病毒本身特殊的分子遗传机制,病毒通过基因点突变和基因组重排快速变异,引发病毒感染宿主范围的改变,持续威胁人类健康,因此,自然界禽流感病毒溢出风险预测具有重... 详细信息

禽流感病毒基因组由8个长短不一的基因节段组成,全长约为14~16 kb。由于病毒本身特殊的分子遗传机制,病毒通过基因点突变和基因组重排快速变异,引发病毒感染宿主范围的改变,持续威胁人类健康,因此,自然界禽流感病毒溢出风险预测具有重要公共卫生意义。文章联合使用卷积神经网络和循环神经网络表征病毒基因组序列,分别在特定类群数据集和全类群数据集上进行训练和测试,并对模型的迁移预测能力进行评估。实验结果显示:①特定类群模型对各自数据集的预测性能良好,AUROC值和AUPR值分别达到0.966和0.876以上,但泛化能力较差;②除H9N2类群外,全局模型性能良好,AUROC值和AUPR值均达到1.000;③基于消融实验,发现注意力机制和Embedding层对模型性能影响较大;④进一步测试模型的泛化能力,迁移预测的AUROC值和AUPR值分别可达0.984和0.941以上;⑤可视化注意力权重系数矩阵,为模型提供生物学可解释性。性能良好的深度学习预测模型可用于禽流感病毒跨种感染的早期预警。

关键词：禽流感病毒深度学习溢出风险基因组

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基于增量学习的冠状病毒人际感染预测研究

广州大学学报（自然科学版） 2024年第2期23卷 37-47页

作者：杨晓宇沈骜沈嘉豪廖玉琼强小利寇铮广州大学计算科技研究院广东广州510006 广州大学计算机科学与网络工程学院广东广州510006

2019年底至今,新型冠状病毒大流行严重影响了公众卫生和社会秩序,而基于机器学习的预测方法可以判别冠状病毒的可感染性表型和大流行风险。目前,已发现6类感染人的冠状病毒,病毒基因组序列差异显著,病毒持续遗传变异导致机器学习模型性... 详细信息

2019年底至今,新型冠状病毒大流行严重影响了公众卫生和社会秩序,而基于机器学习的预测方法可以判别冠状病毒的可感染性表型和大流行风险。目前,已发现6类感染人的冠状病毒,病毒基因组序列差异显著,病毒持续遗传变异导致机器学习模型性能下降并引发潜在的学习遗忘现象。文章基于增量学习的模型框架,使用One-class SVM算法对冠状病毒新类群进行持续鉴别,并进一步使用参数共享和知识蒸馏的联合策略改造BP神经网络,对冠状病毒人际感染表型进行持续学习和预测。结果显示,One-class SVM对6类病毒区分的权衡参数v组合在0.92、0.81、0.24、0.11、0.55、0.20下达到最优的病毒类群分类效果;当隐藏层节点批次增加为6时,预测模型取得最好性能表现,IAC取得最大值0.9035,BT取得最大值-0.0399,有效地抑制了神经网络模型的学习遗忘趋势,模型的预测性能接近联合训练的性能表现(IAC:0.9236),明显优于未使用知识蒸馏的神经网络(IAC:0.7764),进一步与其他增量方法比较,优于基于样本的ESRIL方法(IAC:0.8662)和基于模型参数的CCLL方法(IAC:0.8853),具有重要的公共卫生应用价值。

关键词：增量学习冠状病毒刺突蛋白人际感染

Using amino acid features to identify the pathogenicity of influenza B virus

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Infectious Diseases of Poverty 2022年第3期11卷 88-88页

作者： zheng kou Xinyue Fan Junjie Li Zehui Shao Xiaoli Qiang Institute of Computing Science and Technology Guangzhou UniversityGuangzhou510006China School of Computer Science and Cyber Engineering Guangzhou UniversityGuangzhou510006China

Background:Influenza B virus can cause epidemics with high pathogenicity, so it poses a serious threat to public health. A feature representation algorithm is proposed in this paper to identify the pathogenicity phenotype of influenza B virus.Methods:The dataset included all 11 influenza virus proteins encoded in eight genome segments of 1724 strains. Two types of features were hierarchically used to build the prediction model. Amino acid features were directly delivered from 67 feature descriptors and input into the random forest classifier to output informative features about the class label and probabilistic prediction. The sequential forward search strategy was used to optimize the informative features. The final features for each strain had low dimensions and included knowledge from different perspectives, which were used to build the machine learning model for pathogenicity identification.Results:The 40 signature positions were achieved by entropy screening. Mutations at position 135 of the hemagglutinin protein had the highest entropy value (1.06). After the informative features were directly generated from the 67 random forest models, the dimensions for class and probabilistic features were optimized as 4 and 3, respectively. The optimal class features had a maximum accuracy of 94.2% and a maximum Matthews correlation coefficient of 88.4%, while the optimal probabilistic features had a maximum accuracy of 94.1% and a maximum Matthews correlation coefficient of 88.2%. The optimized features outperformed the original informative features and amino acid features from individual descriptors. The sequential forward search strategy had better performance than the classical ensemble method.Conclusions:The optimized informative features had the best performance and were used to build a predictive model so as to identify the phenotype of influenza B virus with high pathogenicity and provide early risk warning for disease control.

关键词： Influenza B virus Pathogenicity Amino acid feature Machine learning

Pithovirus: a new giant DNA virus found from more than 30,000-year-old sample

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Virologica Sinica 2014年第2期29卷 71-73页

作者： zheng kou Tianxian Li State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences

A third type of giant DNA virus named Pithovirus was recently isolated from a ＞30,000-year-old permafrost sample in Siberia （Legendre M,et al,2014）.Pithovirus has a larger pandoravirus-like particle with 1.5 μm length and its adenine-thymine-rich genome is about 600 kb,which is surprisingly smaller than Pandoravirus.There is very slight genetic relationship between Pithovirus and Pandoravirus and their replication cycles significantly differ.The groundbreaking discovery of this ancient virus expands our understanding of giant DNA viruses and raises the concern of pathogen reemergence from permafrost regions because of the change of climate or the activity of human.

关键词：病毒学临床诊断实验