Protein Microarray: An Ideal Platform for Systems Biology

  • Zong-Xiu Wang
  • Rui-Ping Deng
  • Shu-Juan Guo
  • Ji-Bin Zhang
  • Sheng-Ce Tao
Chapter

Abstract

Systems biology intends to understand the biological systems as a whole, it may hold the key for eventually cure of some of the most challenging complex diseases, such as cancer, diabetes, obesity, mental disorders and etc. The major driving forces of systems biology are high-throughput “-omics” technologies, i.e., genomics, transcriptomics, proteomics and metabolomics and etc. Featured as high-throughput, miniaturized and capable of parallel analyses, protein microarray has already become a powerful tool for systems biology. In this chapter, we will focus on the application of protein microarrays for global analysis of biological systems and clinical samples, especially cancer related studies. We will discuss the four major types of protein microarray, i.e., proteome microarray, antibody microarray, reverse phase protein array (RPA) and lectin microarrays. We will also discuss the challenges that we are facing and the future trends of protein microarray technology and its applications for systems biology. We strongly believe that protein microarrays will become a standard technology in both basic research and clinical study.

Keywords

Systems biology Proteome microarray Antibody microarray Reverse phase protein array (RPA) Cancer 

Abbreviations

RPA

Reverse phase protein array

ORF

Open reading frame

IVTT

In vitro transcription and translation

uDBPs

Unconventional DNA-binding proteins

HATs

Histone acetylases

HDACs

Histone deacetylase

SELEX

Systematic evolution of ligands by exponential enrichment

References

  1. Aldea M, Clofent J, de Nunez AC, Chamorro M, Velasco M, Berrendero JR, Navarro C, Cuezva JM (2011) Reverse phase protein microarrays quantify and validate the bioenergetic signature as biomarker in colorectal cancer. Cancer Lett 311:210–218CrossRefPubMedGoogle Scholar
  2. Alhamdani MS, Schroder C, Hoheisel JD (2010a) Analysis conditions for proteomic profiling of mammalian tissue and cell extracts with antibody microarrays. Proteomics 10:3203–3207CrossRefPubMedGoogle Scholar
  3. Alhamdani MS, Schroder C, Werner J, Giese N, Bauer A, Hoheisel JD (2010b) Single-step procedure for the isolation of proteins at near-native conditions from mammalian tissue for proteomic analysis on antibody microarrays. J Proteome Res 9:963–971CrossRefPubMedGoogle Scholar
  4. Angenendt P, Glokler J, Murphy D, Lehrach H, Cahill DJ (2002) Toward optimized antibody microarrays: a comparison of current microarray support materials. Anal Biochem 309:253–260CrossRefPubMedGoogle Scholar
  5. Auffray C, Chen Z, Hood L (2009) Systems medicine: the future of medical genomics and healthcare. Genome Med 1:2CrossRefPubMedPubMedCentralGoogle Scholar
  6. Barber N, Gez S, Belov L, Mulligan SP, Woolfson A, Christopherson RI (2009) Profiling CD antigens on leukaemias with an antibody microarray. FEBS Lett 583:1785–1791CrossRefPubMedGoogle Scholar
  7. Belov L, de la Vega O, dos Remedios CG, Mulligan SP, Christopherson RI (2001) Immunophenotyping of leukemias using a cluster of differentiation antibody microarray. Cancer Res 61:4483–4489PubMedGoogle Scholar
  8. Belov L, Huang P, Chrisp JS, Mulligan SP, Christopherson RI (2005) Screening microarrays of novel monoclonal antibodies for binding to T-, B- and myeloid leukaemia cells. J Immunol Methods 305:10–19CrossRefPubMedGoogle Scholar
  9. Belov L, Mulligan SP, Barber N, Woolfson A, Scott M, Stoner K, Chrisp JS, Sewell WA, Bradstock KF, Bendall L, Pascovici DS, Thomas M, Erber W, Huang P, Sartor M, Young GA, Wiley JS, Juneja S, Wierda WG, Green AR, Keating MJ, Christopherson RI (2006) Analysis of human leukaemias and lymphomas using extensive immunophenotypes from an antibody microarray. Br J Haematol 135:184–197CrossRefPubMedGoogle Scholar
  10. Berg D, Langer R, Tran K, Walch A, Schuster T, Bronger H, Becker KF (2011) Protein microarray-based comparison of HER2, estrogen receptor, and progesterone receptor status in core biopsies and surgical specimens from FFPE breast cancer tissues. Appl Immunohistochem Mol Morphol 19:300–305CrossRefPubMedGoogle Scholar
  11. Bussow K, Cahill D, Nietfeld W, Bancroft D, Scherzinger E, Lehrach H, Walter G (1998) A method for global protein expression and antibody screening on high-density filters of an arrayed cDNA library. Nucleic Acids Res 26:5007–5008CrossRefPubMedPubMedCentralGoogle Scholar
  12. Cahill DJ (2001) Protein and antibody arrays and their medical applications. J Immunol Methods 250:81–91CrossRefPubMedGoogle Scholar
  13. Chandra H, Reddy PJ, Srivastava S (2011) Protein microarrays and novel detection platforms. Expert Rev Proteomics 8:61–79CrossRefPubMedGoogle Scholar
  14. Charles PT, Goldman ER, Rangasammy JG, Schauer CL, Chen MS, Taitt CR (2004) Fabrication and characterization of 3D hydrogel microarrays to measure antigenicity and antibody functionality for biosensor applications. Biosens Bioelectron 20:753–764CrossRefPubMedGoogle Scholar
  15. Chen CS, Zhu H (2006) Protein microarrays. Biotechniques 40:423, 425, 427CrossRefPubMedGoogle Scholar
  16. Chen CS, Korobkova E, Chen H, Zhu J, Jian X, Tao SC, He C, Zhu H (2008) A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat Methods 5:69–74CrossRefPubMedPubMedCentralGoogle Scholar
  17. Crompton PD, Kayala MA, Traore B, Kayentao K, Ongoiba A, Weiss GE, Molina DM, Burk CR, Waisberg M, Jasinskas A, Tan X, Doumbo S, Doumtabe D, Kone Y, Narum DL, Liang X, Doumbo OK, Miller LH, Doolan DL, Baldi P, Felgner PL, Pierce SK (2010) A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci USA 107:6958–6963CrossRefPubMedPubMedCentralGoogle Scholar
  18. Davies DH, Liang X, Hernandez JE, Randall A, Hirst S, Mu Y, Romero KM, Nguyen TT, Kalantari-Dehaghi M, Crotty S, Baldi P, Villarreal LP, Felgner PL (2005a) Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci USA 102:547–552CrossRefPubMedPubMedCentralGoogle Scholar
  19. Davies DH, McCausland MM, Valdez C, Huynh D, Hernandez JE, Mu Y, Hirst S, Villarreal L, Felgner PL, Crotty S (2005b) Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice. J Virol 79:11724–11733CrossRefPubMedPubMedCentralGoogle Scholar
  20. Delehanty JB (2004) Printing functional protein microarrays using piezoelectric capillaries. Methods Mol Biol 264:135–143PubMedGoogle Scholar
  21. Delehanty JB, Ligler FS (2003) Method for printing functional protein microarrays. Biotechniques 34:380–385PubMedGoogle Scholar
  22. Feilner T, Hultschig C, Lee J, Meyer S, Immink RG, Koenig A, Possling A, Seitz H, Beveridge A, Scheel D, Cahill DJ, Lehrach H, Kreutzberger J, Kersten B (2005) High throughput identification of potential Arabidopsis mitogen-activated protein kinases substrates. Mol Cell Proteomics 4:1558–1568CrossRefPubMedGoogle Scholar
  23. Gelperin DM, White MA, Wilkinson ML, Kon Y, Kung LA, Wise KJ, Lopez-Hoyo N, Jiang L, Piccirillo S, Yu H, Gerstein M, Dumont ME, Phizicky EM, Snyder M, Grayhack EJ (2005) Biochemical and genetic analysis of the yeast proteome with a movable ORF collection. Genes Dev 19:2816–2826CrossRefPubMedPubMedCentralGoogle Scholar
  24. Gulmann C, Sheehan KM, Conroy RM, Wulfkuhle JD, Espina V, Mullarkey MJ, Kay EW, Liotta LA, Petricoin EF III (2009) Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer. J Pathol 218:514–519CrossRefPubMedGoogle Scholar
  25. Haab BB (2001) Advances in protein microarray technology for protein expression and interaction profiling. Curr Opin Drug Discov Devel 4:116–123PubMedGoogle Scholar
  26. Haab BB, Dunham MJ, Brown PO (2001) Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Genome Biol 2:RESEARCH0004CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hermanson G, Chun S, Felgner J, Tan X, Pablo J, Nakajima-Sasaki R, Molina DM, Felgner PL, Liang X, Davies DH (2012) Measurement of antibody responses to Modified Vaccinia virus Ankara (MVA) and Dryvax((R)) using proteome microarrays and development of recombinant protein ELISAs. Vaccine 30:614–625CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hsu KL, Mahal LK (2006) A lectin microarray approach for the rapid analysis of bacterial glycans. Nat Protoc 1:543–549CrossRefPubMedGoogle Scholar
  29. Hsu KL, Pilobello KT, Mahal LK (2006) Analyzing the dynamic bacterial glycome with a lectin microarray approach. Nat Chem Biol 2:153–157CrossRefPubMedGoogle Scholar
  30. Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, Rho HS, Woodard C, Wang H, Jeong JS, Long S, He X, Wade H, Blackshaw S, Qian J, Zhu H (2009) Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell 139:610–622CrossRefPubMedPubMedCentralGoogle Scholar
  31. Hu S, Xie Z, Qian J, Blackshaw S, Zhu H (2011) Functional protein microarray technology. Wiley Interdiscip Rev Syst Biol Med 3:255–268CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hudson ME, Pozdnyakova I, Haines K, Mor G, Snyder M (2007) Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci USA 104:17494–17499CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ideker T, Galitski T, Hood L (2001) A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2:343–372CrossRefPubMedGoogle Scholar
  34. Jeong JS, Jiang L, Albino E, Marrero J, Rho HS, Hu J, Hu S, Vera C, Bayron-Poueymiroy D, Rivera-Pacheco ZA, Ramos L, Torres-Castro C, Qian J, Bonaventura J, Boeke JD, Yap WY, Pino I, Eichinger DJ, Zhu H, Blackshaw S (2012 Jun) Rapid identification of monospecific monoclonal antibodies using a human proteome microarray. Mol Cell Proteomics 11(6):O111.016253. Epub 2012 Feb 3PMID:22307071 (PubMed – in process)Google Scholar
  35. Jones VW, Kenseth JR, Porter MD, Mosher CL, Henderson E (1998) Microminiaturized immunoassays using atomic force microscopy and compositionally patterned antigen arrays. Anal Chem 70:1233–1241CrossRefPubMedGoogle Scholar
  36. Jones RB, Gordus A, Krall JA, MacBeath G (2006) A quantitative protein interaction network for the ErbB receptors using protein microarrays. Nature 439:168–174CrossRefPubMedGoogle Scholar
  37. Kaufman KL, Belov L, Huang P, Mactier S, Scolyer RA, Mann GJ, Christopherson RI (2010) An extended antibody microarray for surface profiling metastatic melanoma. J Immunol Methods 358:23–34CrossRefPubMedGoogle Scholar
  38. Kramer A, Feilner T, Possling A, Radchuk V, Weschke W, Burkle L, Kersten B (2004) Identification of barley CK2alpha targets by using the protein microarray technology. Phytochemistry 65:1777–1784CrossRefPubMedGoogle Scholar
  39. Kung LA, Tao SC, Qian J, Smith MG, Snyder M, Zhu H (2009) Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals new roles for protein glycosylation in eukaryotes. Mol Syst Biol 5:308CrossRefPubMedPubMedCentralGoogle Scholar
  40. Kunnath-Velayudhan S, Salamon H, Wang HY, Davidow AL, Molina DM, Huynh VT, Cirillo DM, Michel G, Talbot EA, Perkins MD, Felgner PL, Liang X, Gennaro ML (2010) Dynamic antibody responses to the Mycobacterium tuberculosis proteome. Proc Natl Acad Sci USA 107:14703–14708CrossRefPubMedPubMedCentralGoogle Scholar
  41. Kuschel C, Steuer H, Maurer AN, Kanzok B, Stoop R, Angres B (2006) Cell adhesion profiling using extracellular matrix protein microarrays. Biotechniques 40:523–531CrossRefPubMedGoogle Scholar
  42. Kusnezow W, Jacob A, Walijew A, Diehl F, Hoheisel JD (2003) Antibody microarrays: an evaluation of production parameters. Proteomics 3:254–264CrossRefPubMedGoogle Scholar
  43. Lin YY, Lu JY, Zhang J, Walter W, Dang W, Wan J, Tao SC, Qian J, Zhao Y, Boeke JD, Berger SL, Zhu H (2009) Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell 136:1073–1084CrossRefPubMedPubMedCentralGoogle Scholar
  44. Lueking A, Horn M, Eickhoff H, Bussow K, Lehrach H, Walter G (1999) Protein microarrays for gene expression and antibody screening. Anal Biochem 270:103–111CrossRefPubMedGoogle Scholar
  45. MacBeath G, Schreiber SL (2000) Printing proteins as microarrays for high-throughput function determination. Science 289:1760–1763PubMedGoogle Scholar
  46. Martiny-Baron G, Haasen D, D’Dorazio D, Voshol J, Fabbro D (2011) Characterization of kinase inhibitors using reverse phase protein arrays. Methods Mol Biol 785:79–107CrossRefPubMedGoogle Scholar
  47. Mochon AB, Ye J, Kayala MA, Wingard JR, Clancy CJ, Nguyen MH, Felgner P, Baldi P, Liu H (2010) Serological profiling of a Candida albicans protein microarray reveals permanent host-pathogen interplay and stage-specific responses during candidemia. PLoS Pathog 6:e1000827CrossRefPubMedPubMedCentralGoogle Scholar
  48. Nilsson P, Paavilainen L, Larsson K, Odling J, Sundberg M, Andersson AC, Kampf C, Persson A, Al-Khalili SC, Ottosson J, Bjorling E, Hober S, Wernerus H, Wester K, Ponten F, Uhlen M (2005) Towards a human proteome atlas: high-throughput generation of mono-specific antibodies for tissue profiling. Proteomics 5:4327–4337CrossRefPubMedGoogle Scholar
  49. Nishizuka S, Charboneau L, Young L, Major S, Reinhold WC, Waltham M, Kouros-Mehr H, Bussey KJ, Lee JK, Espina V, Munson PJ, Petricoin E III, Liotta LA, Weinstein JN (2003a) Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays. Proc Natl Acad Sci USA 100:14229–14234CrossRefPubMedPubMedCentralGoogle Scholar
  50. Nishizuka S, Chen ST, Gwadry FG, Alexander J, Major SM, Scherf U, Reinhold WC, Waltham M, Charboneau L, Young L, Bussey KJ, Kim S, Lababidi S, Lee JK, Pittaluga S, Scudiero DA, Sausville EA, Munson PJ, Petricoin EF III, Liotta LA, Hewitt SM, Raffeld M, Weinstein JN (2003b) Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. Cancer Res 63:5243–5250PubMedGoogle Scholar
  51. Paweletz CP, Charboneau L, Bichsel VE, Simone NL, Chen T, Gillespie JW, Emmert-Buck MR, Roth MJ, Petricoin EF III, Liotta LA (2001) Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene 20:1981–1989CrossRefPubMedGoogle Scholar
  52. Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De VC, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, Snyder M (2005) Global analysis of protein phosphorylation in yeast. Nature 438:679–684CrossRefPubMedGoogle Scholar
  53. Puig-Costa M, Oliveras-Ferraros C, Flaquer S, Llopis-Puigmarti F, Pujol-Amado E, Martin-Castillo B, Vazquez-Martin A, Cufi S, Ortiz R, Roig J, Codina-Cazador A, Menendez JA (2011) Antibody microarray-based technology to rapidly define matrix metalloproteinase (MMP) signatures in patients undergoing resection for primary gastric carcinoma. J Surg Oncol 104:106–109CrossRefPubMedGoogle Scholar
  54. Ramaswamy A, Lin E, Chen I, Mitra R, Morrisett J, Coombes K, Ju Z, Kapoor M (2005) Application of protein lysate microarrays to molecular marker verification and quantification. Proteome Sci 3:9CrossRefPubMedPubMedCentralGoogle Scholar
  55. Reddy ST, Ge X, Miklos AE, Hughes RA, Kang SH, Hoi KH, Chrysostomou C, Hunicke-Smith SP, Iverson BL, Tucker PW, Ellington AD, Georgiou G (2010) Monoclonal antibodies isolated without screening by analyzing the variable-gene repertoire of plasma cells. Nat Biotechnol 28:965–969CrossRefPubMedGoogle Scholar
  56. Schena M, Shalon D, Heller R, Chai A, Brown PO, Davis RW (1996) Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad Sci USA 93:10614–10619CrossRefPubMedPubMedCentralGoogle Scholar
  57. Sheehan KM, Calvert VS, Kay EW, Lu Y, Fishman D, Espina V, Aquino J, Speer R, Araujo R, Mills GB, Liotta LA, Petricoin EF III, Wulfkuhle JD (2005) Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma. Mol Cell Proteomics 4:346–355CrossRefPubMedGoogle Scholar
  58. Song Q, Liu G, Hu S, Zhang Y, Tao Y, Han Y, Zeng H, Huang W, Li F, Chen P, Zhu J, Hu C, Zhang S, Li Y, Zhu H, Wu L (2010) Novel autoimmune hepatitis-specific autoantigens identified using protein microarray technology. J Proteome Res 9:30–39CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sreekumar A, Nyati MK, Varambally S, Barrette TR, Ghosh D, Lawrence TS, Chinnaiyan AM (2001) Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res 61:7585–7593PubMedGoogle Scholar
  60. Stillman BA, Tonkinson JL (2000) FAST slides: a novel surface for microarrays. Biotechniques 29:630–635PubMedGoogle Scholar
  61. Stoll D, Templin MF, Schrenk M, Traub PC, Vohringer CF, Joos TO (2002) Protein microarray technology. Front Biosci 7:c13–c32CrossRefPubMedGoogle Scholar
  62. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefPubMedGoogle Scholar
  63. Tao SC, Chen CS, Zhu H (2007) Applications of protein microarray technology. Comb Chem High Throughput Screen 10:706–718CrossRefPubMedGoogle Scholar
  64. Tao SC, Li Y, Zhou J, Qian J, Schnaar RL, Zhang Y, Goldstein IJ, Zhu H, Schneck JP (2008) Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiology 18:761–769CrossRefPubMedPubMedCentralGoogle Scholar
  65. Tateno H, Kuno A, Itakura Y, Hirabayashi J (2010) A versatile technology for cellular glycomics using lectin microarray. Methods Enzymol 478:181–195CrossRefPubMedGoogle Scholar
  66. Tateno H, Toyota M, Saito S, Onuma Y, Ito Y, Hiemori K, Fukumura M, Matsushima A, Nakanishi M, Ohnuma K, Akutsu H, Umezawa A, Horimoto K, Hirabayashi J, Asashima M (2011) Glycome diagnosis of human induced pluripotent stem cells using lectin microarray. J Biol Chem 286:20345–20353CrossRefPubMedPubMedCentralGoogle Scholar
  67. Templin MF, Stoll D, Schrenk M, Traub PC, Vohringer CF, Joos TO (2002) Protein microarray technology. Trends Biotechnol 20:160–166CrossRefPubMedGoogle Scholar
  68. Toyoda M, Yamazaki-Inoue M, Itakura Y, Kuno A, Ogawa T, Yamada M, Akutsu H, Takahashi Y, Kanzaki S, Narimatsu H, Hirabayashi J, Umezawa A (2011) Lectin microarray analysis of pluripotent and multipotent stem cells. Genes Cells 16:1–11CrossRefPubMedGoogle Scholar
  69. Wingren C, Borrebaeck CA (2008) Antibody microarray analysis of directly labelled complex proteomes. Curr Opin Biotechnol 19:55–61CrossRefPubMedGoogle Scholar
  70. Wingren C, Ingvarsson J, Dexlin L, Szul D, Borrebaeck CA (2007) Design of recombinant antibody microarrays for complex proteome analysis: choice of sample labeling-tag and solid support. Proteomics 7:3055–3065CrossRefPubMedGoogle Scholar
  71. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920CrossRefPubMedGoogle Scholar
  72. Zheng D, Wan J, Cho YG, Wang L, Chiou CJ, Pai S, Woodard C, Zhu J, Liao G, Martinez-Maza O, Qian J, Zhu H, Hayward GS, Ambinder RF, Hayward SD (2011) Comparison of humoral immune responses to Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus using a viral proteome microarray. J Infect Dis 204:1683–1691CrossRefPubMedPubMedCentralGoogle Scholar
  73. Zhou J, Belov L, Huang PY, Shin JS, Solomon MJ, Chapuis PH, Bokey L, Chan C, Clarke C, Clarke SJ, Christopherson RI (2010) Surface antigen profiling of colorectal cancer using antibody microarrays with fluorescence multiplexing. J Immunol Methods 355:40–51CrossRefPubMedGoogle Scholar
  74. Zhu H, Snyder M (2003) Protein chip technology. Curr Opin Chem Biol 7:55–63CrossRefPubMedGoogle Scholar
  75. Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P, Lan N, Jansen R, Bidlingmaier S, Houfek T, Mitchell T, Miller P, Dean RA, Gerstein M, Snyder M (2001) Global analysis of protein activities using proteome chips. Science 293:2101–2105CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Zong-Xiu Wang
    • 1
    • 2
    • 3
  • Rui-Ping Deng
    • 1
    • 2
  • Shu-Juan Guo
    • 1
    • 2
  • Ji-Bin Zhang
    • 3
  • Sheng-Ce Tao
    • 1
    • 2
  1. 1.Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education)Shanghai Jiao Tong UniversityShanghaiChina
  2. 2.State Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong UniversityShanghaiChina
  3. 3.National Key Laboratory of Agricultural Microbiology, College of Life Science and TechnologyHuazhong Agricultural UniversityWuhanChina

Personalised recommendations