title: Localized-statistical quantification of human serum proteome associated with type 2 diabetes.
abstract: BACKGROUND
  Recent advances in proteomics have shed light to discover serum proteins or peptides as biomarkers for tracking the progression of diabetes as well as understanding molecular mechanisms of the disease.
  
  
  RESULTS
  In this work, human serum of non-diabetic and diabetic cohorts was analyzed by proteomic approach. To analyze total 1377 high-confident serum-proteins, we developed a computing strategy called localized statistics of protein abundance distribution (LSPAD) to calculate a significant bias of a particular protein-abundance between these two cohorts. As a result, 68 proteins were found significantly over-represented in the diabetic serum (p<0.01). In addition, a pathway-associated analysis was developed to obtain the overall pathway bias associated with type 2 diabetes, from which the significant over-representation of complement system associated with type 2 diabetes was uncovered. Moreover, an up-stream activator of complement pathway, ficolin-3, was observed over-represented in the serum of type 2 diabetic patients, which was further validated with statistic significance (p = 0.012) with more clinical samples.
  
  
  CONCLUSIONS
  The developed LSPAD approach is well fit for analyzing proteomic data derived from biological complex systems such as plasma proteome. With LSPAD, we disclosed the comprehensive distribution of the proteins associated with diabetes in different abundance levels and the involvement of ficolin-related complement activation in diabetes.
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rong-Xia
authors.initials: RX
authors.lastname: Li
authors.forename: Hai-Bing
authors.initials: HB
authors.lastname: Chen
authors.forename: Kang
authors.initials: K
authors.lastname: Tu
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Zhao
authors.forename: Hu
authors.initials: H
authors.lastname: Zhou
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.forename: Qing-Run
authors.initials: QR
authors.lastname: Li
authors.forename: Song
authors.initials: S
authors.lastname: Nie
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Li
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Jia
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Wu
mesh_terms: D000368:Aged; D015415:Biomarkers; D001798:Blood Proteins / Q000737:chemistry*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism*; D018450:Disease Progression; D004587:Electrophoresis, Agar Gel / Q000379:methods; D006801:Humans; D037102:Lectins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D000097604:Ficolins
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D037102:Lectins; D000097604:Ficolins
references.citation: Diabetes Care. 1999 May;22(5):767-72
references.pmid: 10332679
references.citation: J Proteome Res. 2005 Mar-Apr;4(2):613-9
references.pmid: 15822942
references.citation: Diabetes. 2004 Jun;53(6):1570-6
references.pmid: 15161763
references.citation: J Am Soc Nephrol. 2001 Jul;12(7):1549-1557
references.pmid: 11423586
references.citation: J Proteome Res. 2005 Jul-Aug;4(4):1265-73
references.pmid: 16083276
references.citation: Clin Chim Acta. 2005 Nov;361(1-2):10-9
references.pmid: 15996650
references.citation: Proteomics. 2005 Jul;5(10):2619-30
references.pmid: 15892164
references.citation: Atherosclerosis. 2006 Jun;186(2):396-401
references.pmid: 16140307
references.citation: Proteome Sci. 2006 Dec 12;4:22
references.pmid: 17163994
references.citation: Adv Exp Med Biol. 2007;598:93-104
references.pmid: 17892207
references.citation: Horm Metab Res. 2003 May;35(5):308-12
references.pmid: 12916001
references.citation: Diabetes. 2002 May;51(5):1609-17
references.pmid: 11978663
references.citation: Arch Intern Med. 2006 Oct 9;166(18):2007-13
references.pmid: 17030835
references.citation: J Biol Chem. 1997 Oct 10;272(41):25576-82
references.pmid: 9325276
references.citation: Proteomics. 2008 Apr;8(7):1516-27
references.pmid: 18383005
references.citation: Mol Cell Proteomics. 2002 Nov;1(11):845-67
references.pmid: 12488461
references.citation: Proteomics. 2001 Dec;1(12):1503-6
references.pmid: 11747208
references.citation: Lancet. 1999 May 15;353(9165):1649-52
references.pmid: 10335783
references.citation: Diabetes. 2005 Feb;54(2):570-5
references.pmid: 15677517
references.citation: J Proteome Res. 2002 Jul-Aug;1(4):375-80
references.pmid: 12645894
references.citation: Science. 1989 Jun 23;244(4911):1483-7
references.pmid: 2734615
references.citation: Autoimmunity. 2003 May;36(3):177-81
references.pmid: 12911285
references.citation: Metabolism. 2002 Jul;51(7):838-42
references.pmid: 12077727
references.citation: Proteomics. 2004 Jan;4(1):244-56
references.pmid: 14730686
references.citation: Biochemistry. 1994 Mar 1;33(8):1988-93
references.pmid: 8117655
references.citation: Diabetes. 2002 May;51(5):1596-600
references.pmid: 11978661
references.citation: Nature. 1997 Apr 3;386(6624):506-10
references.pmid: 9087411
references.citation: Rev Inst Med Trop Sao Paulo. 1994 Sep-Oct;36(5):479
references.pmid: 7569618
references.citation: Diab Vasc Dis Res. 2005 May;2(2):54-60
references.pmid: 16305059
references.citation: Med Hypotheses. 2008;70(2):424-9
references.pmid: 17553627
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10852-7
references.pmid: 16043703
references.citation: Diabetes Res Clin Pract. 2004 Oct;66(1):41-7
references.pmid: 15364160
references.citation: J Biol Chem. 1996 Jan 19;271(3):1776-83
references.pmid: 8576182
references.citation: J Lipid Res. 1988 Mar;29(3):273-8
references.pmid: 3379339
references.citation: Atherosclerosis. 2003 Apr;167(2):257-64
references.pmid: 12818408
references.citation: Proteomics. 2005 Aug;5(13):3442-53
references.pmid: 16047309
references.citation: Ann Fam Med. 2005 Jan-Feb;3(1):60-3
references.pmid: 15671192
references.citation: Horm Metab Res. 2005 Apr;37 Suppl 1:95-8
references.pmid: 15918118
references.citation: J Biol Chem. 1999 Oct 29;274(44):31286-90
references.pmid: 10531326
references.citation: Mol Cell Proteomics. 2003 Jun;2(6):399-404
references.pmid: 12851465
references.citation: Proteomics. 2006 Jan;6(2):721-30
references.pmid: 16419016
references.citation: Curr Opin Lipidol. 2004 Jun;15(3):261-7
references.pmid: 15166781
references.citation: J Lipid Res. 2004 Jun;45(6):993-1007
references.pmid: 15060092
references.citation: Med Hypotheses. 2007;69(6):1272-6
references.pmid: 17553629
references.citation: Diabetologia. 1997 Nov;40(11):1286-92
references.pmid: 9389420
references.citation: Proc Natl Acad Sci U S A. 1984 Mar;81(5):1356-60
references.pmid: 6424116
references.citation: Immunobiology. 1998 Aug;199(2):348-57
references.pmid: 9777418
references.citation: Mol Genet Metab. 2008 Apr;93(4):481-4
references.pmid: 18055244
references.citation: Metabolism. 1989 Nov;38(11):1042-6
references.pmid: 2478861
references.citation: Proteomics. 2005 Apr;5(5):1431-45
references.pmid: 15761960
references.citation: Arch Intern Med. 2003 Jan 13;163(1):93-9
references.pmid: 12523922
references.citation: Semin Liver Dis. 1997;17(4):297-310
references.pmid: 9408965
references.citation: J Lipid Res. 2003 Jul;44(7):1387-94
references.pmid: 12700345
references.citation: Altern Med Rev. 2001 Jun;6(3):248-71
references.pmid: 11410071
references.citation: Clin Chem. 2005 Feb;51(2):351-9
references.pmid: 15528295
references.citation: Clin Immunol. 2008 Jun;127(3):394-400
references.pmid: 18533284
references.citation: Circ J. 2007 Jun;71(6):868-73
references.pmid: 17526982
references.citation: Diabetes. 2002 Apr;51(4):1131-7
references.pmid: 11916936
references.citation: Free Radic Biol Med. 2007 Sep 1;43(5):730-9
references.pmid: 17664137
references.citation: Atherosclerosis. 1994 Jan;105(1):25-34
references.pmid: 8155085
references.citation: Diabetes Metab. 2003 Sep;29(4 Pt 2):6S9-18
references.pmid: 14502096
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references.pmid: 10592173
references.citation: Immunol Today. 1995 Feb;16(2):58-61
references.pmid: 7888067
references.citation: JAMA. 2001 Jul 18;286(3):327-34
references.pmid: 11466099
references.citation: J Am Coll Cardiol. 2007 May 1;49(17):1798-805
references.pmid: 17466231
references.citation: J Clin Invest. 2007 Mar;117(3):746-56
references.pmid: 17332893