1. 国防科技创新特区项目，新发病毒重配模式及变异趋势的预测（17-163-12-ZT-005-053-01），课题负责人，在研；

2. 中国医学科学院青年医学人才奖励项目，寨卡病毒感染介导小头症发生的免疫损伤机制(2018RC310022)，课题负责人，在研；

3. 国家重点研发计划，重大突发动物源性人兽共患病跨种感染与传播机制研究（2016YFD0500300），子任务负责人，在研；

4. 中国医学科学院医学与健康科技创新工程，系统医学技术研究与应用（2016-I2M-1-005），子课题负责人，在研；

5. 江苏省“六大人才高峰”高层次人才项目，传染病患者免疫状态的系统和定量监测 （SWYY-169），课题负责人，在研；

6. 中国科学院模式识别国家重点实验室开放课题，整合组织样本及单细胞测序数据的免疫细胞组成性模式识别（201900004），课题负责人，在研；

7. 国家自然科学基金（面上项目），流感病毒NA蛋白上位点突变的功能约束和进化选择机制（31470273），课题负责人，结题；

8. 国家自然科学基金（青年基金），人流感病毒抗原性和受体亲和性之间的进化关系及其分子机制（31100950），课题负责人，结题；

主持“国防科技创新特区项目”1项、国家自然自然科学基金2项和国家重点实验室开放课题1项，参与“国家重点研发计划”1项和中国医学科学院医学与健康科技创新工程项目1项，获江苏省“六大人才高峰”高层次项目资助1项，获中国医学科学院青年医学人才项目资助1项。

成果概述      

        本人的研究领域是传染病的计算与系统生物学，专注于发展计算方法和系统整合策略研究重大传染病流行变异及宿主感染的分子机制，进而推动疾病的前瞻性预防控制。近十年的研究中，主要选用流感、寨卡和新冠作为重大新发突发传染病模型，在病毒的起源追溯、变异进化及宿主免疫等方向有相对系统的探索和进展。

（1 ）在病毒溯源环节，开发了多源数据整合的溯源策略，发现了2013年中国人群中爆发的流感H7N9病毒的详细起源路径和来源宿主，成果发表后被作为亮点文章推荐（Cell Host & Microbe 2013）；用类似的溯源策略，合作发现了2015年巴西地区爆发的寨卡病毒与早先蚊子中分离毒株的基因组相似性，为寨卡病毒的蚊媒传播提供了最早的分子证据（Cell Host & Microbe 2016）。在新型冠状病毒爆发的早期，系统刻画了新型冠状病毒SARS-CoV-2与SARS病毒的进化关系和遗传多样性（Cell Host& Microbe 2020）。

（2）在病毒变异进化层面，发展了基于病毒序列和结构特征的抗原变异预测模型（Genome Research 2008）和抗原距离定量模型（PLoSComputational Biology 2010），进而系统地研究了季节性流感H3N2和H1N1在全球不同地区的抗原变异和进化模式，并发现了中国南方地区在全球流感流行中的重要地位（Scientific Reports 2015）。进一步，为了系统度量每个位点在整个流感病毒进化历史中的抗原贡献，我们开发了基于机器学习的抗原决定性位点识别方法RECDS，鉴定出了季节性流感H3N2和H1N1各自最关键的15个抗原类替换决定性位点，为病毒的变异监测和疫苗推荐提供了重要参考（Molecular Biology & Evolution 2019）。

（3）在病毒侵染后的宿主免疫信号定量层面，已经开发了一个基于表达谱数据的组织样本中25种免疫细胞组分的预测模型array-ImmuCC (Scientific Reports2017)，基于转录组测序数据的免疫细胞组分预测模型seq-ImmuCC (Frontiersin Immunology 2018)，以及整合单细胞测序数据的组织特异性免疫组分预测模型tissue-ImmuCC（Bioinformatics 2020）。我们将模型成功应用于流感和寨卡等传染病的组织免疫状态定量研究中，发现了病毒感染后的免疫细胞动态变化规律。建立了在线服务器ImmuCC，上线以来已经为全球数十个课题组提供大量计算任务分析支持。

代表性文章

       (*)和(†) 分别表示（共同）第一或通讯作者.

1.     Wu A*, Niu P*, Wang L*, ZhouH*, Zhao X*, Wang W*, Wang J*, Ji C,Ding X, Wang X, Lu R, Gold S, Aliyari S, Zhang S, Vikram E, Zou A, Lenh E, ChenJ, Ye F, Han N, Peng Y, Guo H, Wu G†, Jiang T†, Tan W†, Cheng G†. Mutations, Recombination andInsertion in the Evolution of 2019-nCoV. bioRxiv (preprint). doi: https://doi.org/10.1101/2020.02.29.971101.

2.     Wu A*, Peng Y*, Huang B*, Ding X*, Wang X,Niu P, Meng J, Zhu Z, Zhang Z, Wang J, Sheng J, Quan L, Xia Z, Tan W†, Cheng G†, Jiang T†. Genomecomposition and divergence of the novel coronavirus (2019-nCoV) originating inChina. Cell Host & Microbe 2020, 27(3):325-328. doi:10.1016/j.chom.2020.02.001. 

3.     Ding X, Yuan X, Wu A†, Jiang T†. Flu Reassort: An integrated reassortment events database for influenzaviruses. Briefings in Bioinformatics 2019, doi: 10.1093/bib/bbz128.

4.     Chen Z, Ji C, Shen Q, Liu W, Qin F. X., Wu A†. Tissue-specific deconvolution of immune cell composition byintegrating bulk and single-cell transcriptomes. Bioinformatics 2019, DOI:10.1093/bioinformatics/btz672.

5.     Sun J, Wang J, Yuan X, Wu X, Sui T, Wu A†, Cheng G†, Jiang T†. Regulation of early host immuneresponses shapes the pathogenicity of avian influenza A virus. Frontiers in Microbiology 2019,DOI:10.3389/fmicb.2019.02007. 

6.     Quan L, Ji C, Ding X, Peng Y, Liu M, Sun J, Jiang T, Wu A†. Cluster-transition determining sites underlying the antigenicevolution of seasonal influenza viruses. Molecular Biology and Evolution 2019, pii: msz050. doi:10.1093/molbev/msz050. 

7.     Wu A†. Viral diseases meetomics: time for systems virology. Science China Life Sciences 2018,61(10): 1274-1276.

8.     Zhao M, Liu K, Luo J, Tan S, Quan C, Zhang S, Chai Y, Qi J, Li Y, Bi Y, XiaoH, Wong G,  Zhou J, Jiang T, Liu W, Yu H,Yan J, Liu Y, Shu Y, Wu G, Wu A†, Gao GF†, Liu WJ†. Heterosubtypic protectionsagainst human- infecting avian influenza viruses correlate to biasedcross-T-cell responses. mBio 2018, 9:e01408- 18.

9.     Jiang H, Sun J, ChenY, Chen Z, Wang L, Gao W, Shi Y, Zhang W, Mei Y, Chokkakula S, Wissa V, Jiang T†, Wu A† and Wang H†. Landscape of thegenome and host cell response of Mycobacterium shigaense reveals pathogenicfeatures. Emerg Microbes Infect 2018, 7(1): 112.

10.  Chen Z, Quan L, Huang A, Zhao Q, Yuan Y, Yuan X, Shen Q,Shang J, Ben Y, Qin FX-F†and Wu A†. seq-ImmuCC: Cell-Centric View of Tissue TranscriptomeMeasuring Cellular Compositions of Immune Microenvironment From Mouse RNA-SeqData. Frontiers in Immunology 2018, 9:1286. doi: 10.3389/fimmu.2018.01286.

11. Chen Z, Huang A, Sun J, Jiang T, Qin F.X.F†, Wu A†. Inference of immune cellcomposition on the expression profiles of mouse tissue. Scientific Reports 2017,7: 40508, doi: 10.1038/srep40508. 

12. Wang L, Valderramos S, Wu A, Ouyang S, Li C, Brasil P, Bonaldo M, Coates T, Nielsen-SainesK, Jiang T, Aliyari R, Cheng G. From mosquitos to humans: Genetic evolution ofZika virus. Cell Host & Microbe 2016, 19(5): 561-565. 

13. Wu A*, Su C*,Wang D*, Peng Y*, Liu M, Hua S, Li T, Gao F, Tang H, ChenJ, Liu X, Shu Y, Peng D, Jiang T. Sequential reassortments underlie diverseinfluenza H7N9 genotypes in China. Cell Host & Microbe 2013, DOI: 10.1016/j.chom.2013.09.001. 

14. Wu A*, Peng Y*,Du X, Shu Y, Jiang T, Correlation of Influenza Virus Excess Mortality withAntigenic Variation: Application to Rapid Estimation of Influenza MortalityBurden, PLoS Computational Biology, 2010, 6(8): e1000882. 

15. Du X*, Wang Z*, Wu A*, Song L, Cao Y, HangH, and Jiang T. Networks of genomic co-occurrence capture characteristics ofhuman influenza A (H3N2) evolution. Genome Research 2008, 18(1): 178-187. 

其他发表文章

       (*)和(†) 分别表示（共同）第一或通讯作者.

1.     Sun J*, Ye F*, Wu A*, Yang R*, Pan M, Sheng J , Zhu W, Mao L,Wang M, Huang B†, Tan W†, Jiang T†. Comparative transcriptome analysis reveals the intensive early-stageresponses of host cells to SARS-CoV-2 infection. bioRxiv (preprint). doi:10.1101/2020.04.30.071274.

2.     Peng Y, Wu A, Meng J, Yang L,Wang D†, Shu Y†, Jiang T†. Automatedrecommendation of the seasonal influenza vaccine strain with PREDAC. Biosafety and Health. doi:http://dx.doi.org/10.1016/j.bsheal.2020.04.002.

3.     Zhang Z*, Ye S*, Wu A, Jiang T, Peng Y†.Prediction of the receptorome for the human-infecting virome. bioRxiv(preprint). doi: https://doi.org/10.1101/2020.02.27.967885.

4.     Zhang Z, Yu F, Zou Y, Qiu Y, Wu A,Jiang T†, Peng Y†. Phage protein receptors have multipleinteraction partners and high expressions. Bioinformatics, 2020, 1–5. doi:10.1093/bioinformatics/btaa123.

5.     Lu C*, Cai Z*, Zou Y, Zhang Z, Chen W, Deng L, DuX, Wu A, Yang L, Wang D, Shu Y,Jiang T†, Peng Y†. FluPhenotype—a one-stop platform for early warnings of the influenza Avirus. Bioinformatics, 2020, 1–3. doi: 10.1093/bioinformatics/btaa083.

6.     Peng Y*†, Zhu W*, Feng Z, Zhu Z, Zhang Z,Chen Y, Liu S, Wu A, Wang D, Shu Y†, Jiang T†.Identification of genome-widenucleotide sitesassociated with mammalian virulence in influenza A viruses. BiosafetyandHealth (2020). doi: https://doi.org/10.1016/j.bsheal.2020.02.006.

7.     Wang H*†, Jiang H*, Teles R*,Chen Y, Wu A, Lu J, Chen Z, Ma F,Pellegrini M, Modlin RL†. Cellular, molecular and immunologicalcharacteristics of Langhans multinucleated giant cells programmed by IL-15. TheJournal of Investigative Dermatology (2020). doi:https://doi.org/10.1016/ j.jid.2020.01.026.

8.     Sun X, Shang J, Wu A,  XiaJ† , Xu F†. Identification of dynamic signatures associated with smokingrelatedsquamous cell lung cancer and chronic obstructive pulmonary disease. Journalof Cellular and Molecular Medicine 2019. doi: 10.1111/jcmm.14852.

9.     Liu W†,Pellegrini M, Wu A†.Identification of bridging centrality in complex networks. IEEE Access2019, 7:93123-93130.

10.  Li C, Deng YQ, Zu S, Quanquin N, Shang J, Tian M, Ji X, Zhang NN, DongHL, Xe YP, Zhao LZ, Zhang FC, Li XF, WuA, Cheng G, Qin CF. Zika virus shedding in the stool and infection throughthe anorectal mucosa in mice. Emerg Microbes Infect 2018, 7(1):169.

11.  Zhang Z, Zhu Z, Chen W, Cai Z, Xu B, Tan Z, Wu A, Gen X, Guo X, Tan Z, Xia Z, Zhu H, Jiang T, Peng Y. Cellmembrane proteins with high N-glycosylation, high expression, and multipleinteraction partners are prefered by mammalian viruses as receptors. Bioinformatics2018, doi: 10.1093/bioinformatics/bty694.

12. Luo J, Deng L, Ding X, Quan L, Wu A†, Jiang T†. Hydrogenbond variations of influenza A viruses during adaptation in human. ScientificReports 2017, 7: 14295.

13. Ding X, Luo J Quan L, Wu A†, Jiang T†.Evolutionary genotypes of influenza A (H7N9) viruses over five epidemic wavesin China. Infection, Genetics and Evolution 2017, 55,10.1016/j.meegid.2017.09.027.

14. Weiss DI, Dang AT, Montoya D, Wu A, Gilliet M, Pellegrini M, Modlin RL. Innate activation of Th17cells triggers IL-26 release. Journal of Immunology 2017, 198,61.4.

15. Li T, Yao H, Liu D, Ren H, Hu Y, Kargbo D, Teng Y,Deng Y, Lu H, Liu X, Liu K, Fang L, Ning N, Wang G, Dafae F, Kamar A, Wu A, Jiang T, Li Z, Huang J, Sun Y,Qian J, Kargbo B, Jiang J, Wang H, Cao W. Mapping the clinical outcomes andgenetic evolution of Ebola virus in Sierra Leone. JCI insight 2017, 2(14):e88333.

16. Peng Y, Li X, Zhou H, Wu A, Dong L, Zhang Y, Gao R, Bo H, Yang L, Wang D, Lin X, Jin M,Shu Y and Jiang T. Continual antigenic diversification in China leads to globalantigenic complexity of avian influenza H5N1 viruses. Scientific Reports 2017,7:43566, doi: 10.1038/srep43566.

17. Zou Y, Wu Z, Deng L, Wu A, Wu F, Li K, Jiang T, Peng Y. cooccurNet: an R package forco-occurrence network construction and analysis. Bioinformatics 2017, btx062.doi: 10.1093/bioinformatics/btx062.

18. Xu X*,Wu A*, Zhang X, Su M,Jiang T, Yuan Z. MetaDP: a comprehensive web server for disease prediction of16S rRNA metagenomic datasets. Biophys Rep 2017. Doi:10.1007/s41048-016-0033-4.

19. Dai W*,Wu A*, Ma L, Li Y, JiangT, Li Y. A novel index of protein-protein interface propensity improvesinterface residue recognition. BMC Systems Biology 2016, 10(Suppl4):112.

20. Liu M, Zhao X, Hua S, Du X, Peng Y, Li X, Lan Y, WangD, Wu A†, Shu Y†& Jiang T†. Antigenic patterns andevolution of the human influenza A (H1N1) virus. Scientific Reports 2015,5:14171.

21. Wang Y, Qu J, Ba Q, Dong J, Zhang L, Zhang H, Wu A, Qang D, Xia Z, Peng D, Shu Y, CaoB, Jiang T. Detection and typing of human-infecting influenza viruses in Chinaby using a multiplex DNA biochip assay. J Virol Methods 2016, 234: 178-185.

22. Wang L*, Wu A*, Wang E. Y*, QuanquinN, Li C, Wang J, Chen H, Liu S, Liu P, Liu Y, Qin X, Jiang T†, Cheng G†.Functional genomics reveals linkers critical for influenza polymerase. JVirol 2016, 90(6): 2938-2947.

23. Peng Y, Yang L, Li H, Zou Y, Deng L, Wu A, Du X, Wang D, Shu Y, Jiang T.PREDAC-H3: a user-friendly platform for antigenic surveillance of humaninfluenza A(H3N2) virus based on hemagglutinin sequences. Bioinformatics 2016,32(16): 2526-2527.

24. Liu W, Wu A,Pellegrini M, Wang X. Integrative analysis of human protein, function and diseasenetworks. Scientific Reports 2015, DOI: 10.1038/srep14344.

25. Hua S, Li X, Liu M, Cheng Y, Peng Y, Huang W, Tan M,Wei H, Guo J, Wang D, Wu A†, Shu Y†& Jiang T†. Antigenic variation ofhuman influenza A (H3N2) viruses during the 2014-15 winter season. SciChina Life Sci 2015.

26. Liu M, Song T, Hua S, Wu A† & Jiang T†. Computational analysis ofantigenic epitopes of avian influenza A (H7N9) viruses. Sci China Life Sci 2015,DOI: 10.1007/s11427-015-4886-4.

27. Deng L, Liu M, Hua S, Peng Y, Wu A, Qin F. X, Cheng G, Jiang T. Network of co-mutations in Ebolavirus genome predicts the disease lethality. Cell Research 2015, 25:753-756.

28. Ma F, Li B, Liu S, Iyer S. S, Yu Y, Wu A, Cheng G. Positive feedbackregulation of type I IFN production by the IFN-inducible DNA sensor cGAS. Journalof Immunology 2015, 194(4): 1545-54.

29. Ma M, Yang X, Qian Y, Zhao S, Hua S, Wang T, Chen S,Ma G, Sang X, Liu L, Wu A, Jiang T,Gao Y, Gray G, Zhao T, Ling X, Wang J, Lu B, Qian J, Cao W. Characterization ofa novel reassortant influenza A virus (H2N2) from a domestic duck in easternChina. Scientific Reports 4, 2014, doi:10.1038/srep07588.

30. Li H, Peng Y, Zou Y, Huang Z, Wu A, Li K, Jiang T. PREDAC-H5: A user-friendly tool for theautomated surveillance of antigenic variants for the HPAI H5N1 virus. Infection,genetics and evolution 2014, 28: 62-63.

31. Li C*,Wu A*, Peng Y, Wang J,Guo Y, Chen Z, Zhang H, Wang Y, Dong J, Wang L, Qing F. X, Cheng G, Deng T,Jiang T. Integrating computational modeling and functional assays to decipher thestructure-function relationship of influenza virus PB1 protein. ScientificReports 4, 2014, doi:10.1038/srep07192.

32. Wang D, Yang L, Gao R, Zhang X, Tan Y, Wu A, Zhu W, Zhou J, Li X, Sun Y, Zhang Y, Liu Y, Liu T, Xiong Y, Xu J, ChenL, Weng Y, Qi X, Guo J, Li X, Dong J, Huang W, Zhang Y, Dong L, Zhao X, Liu L,Lu J, Lan Y, Wei H, Xin L, Chen Y, Xu C, Chen T, Zhu Y, Jiang T, Feng Z, YangW, Wang Y, Zhu H, Guan Y, Gao G, Li D, Han J, Wang S, Wu G, Shu Y. Genetictuning of the novel avian influenza A (H7N9) virus during interspeciestransmission, China, 2013. Euro Surveillance 2014, 19(25):pii=20699.

33. Deng L*, Wu A*, Dai W, Song T, Cui Y, Jiang T. Exploring proteindomain organization by recognition of secondary structure packing interfaces. Bioinformatics2014, doi:10.1093/bioinformatics/btu327.

34. Deng L, Dong X, WuA, Song T, Jiang T. Coevolution signals capture the specific packing ofsecondary structures in protein architecture. Protein Cell, 2014, 5(6):480-483.

35. Dai W, Song T,Wang X, Jin X, Deng L, Wu A† & Jiang T†. Improvementin Low-Homology Template-Based Modeling by Employing a Model Evaluation Methodwith Focus on Topology. PLoS ONE 2014, 9(2): e89935. doi: 10.1371/journal.pone.0089935.

36. Li C, Ba Q, WuA, Zhang H, Jiang T. A peptide derived from C-terminus of PB1 inhibitsinfluenza virus replication by interfering with viral polymerase assembly. FEBSJ 2013, 280(4): 1139-49.

37. Du X, Dong L, Lan Y, Peng Y, Wu A, Zhang Y,Huang W, Wang D, Wang M, Guo Y, Shu Y, Jiang T, Mapping of H3N2 InfluenzaAntigenic Evolution in China Reveals a Strategy for Vaccine StrainRecommendation. Nature Communications 2012, 3:709.

38. Hu Y, Dong X, Wu A, Cao, Y, Tian L,Jiang T. Incorporation of local structural preference potentialimproves fold recognition, PLoS One 2011, 6(2): e17215.

39. Cao Y, KohXY, Dong L, Du X, Wu A, Ding X, DengH, Shu Y, Chen J, Jiang T. Rapid estimation of binding activity of influenzavirus hemagglutinin to human and avian recpetors. PloS One 2011, 6(4):e18664.

40. Tian L*, Wu A*, Cao Y, Dong X, Hu Y, Jiang T. NCACO-score:An effective main-chain dependent scoring function for structure modeling, BMCBioinformatics 2011, 12:208-219.

41. Zhao L*, Wu A*, Bi L, Liu P, Zhang X, Jiang T,Jin G, Qi Z. Length-dependent regulation of the Kv1.2 channel activation by itsC-terminus. Molecular Membrane Biology, 2009, 26(3): 186-193