Localized-statistical quantification of human serum proteome associated with type 2 diabetes.
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.
Li
Rong-Xia
RX
Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Chen
Hai-Bing
HB
Tu
Kang
K
Zhao
Shi-Lin
SL
Zhou
Hu
H
Li
Su-Jun
SJ
Dai
Jie
J
Li
Qing-Run
QR
Nie
Song
S
Li
Yi-Xue
YX
Jia
Wei-Ping
WP
Zeng
Rong
R
Wu
Jia-Rui
JR
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
D015415:Biomarkers; D001798:Blood Proteins; D037102:Lectins; D000097604:Ficolins
Diabetes Care. 1999 May;22(5):767-72
10332679
J Proteome Res. 2005 Mar-Apr;4(2):613-9
15822942
Diabetes. 2004 Jun;53(6):1570-6
15161763
J Am Soc Nephrol. 2001 Jul;12(7):1549-1557
11423586
J Proteome Res. 2005 Jul-Aug;4(4):1265-73
16083276
Clin Chim Acta. 2005 Nov;361(1-2):10-9
15996650
Proteomics. 2005 Jul;5(10):2619-30
15892164
Atherosclerosis. 2006 Jun;186(2):396-401
16140307
Proteome Sci. 2006 Dec 12;4:22
17163994
Adv Exp Med Biol. 2007;598:93-104
17892207
Horm Metab Res. 2003 May;35(5):308-12
12916001
Diabetes. 2002 May;51(5):1609-17
11978663
Arch Intern Med. 2006 Oct 9;166(18):2007-13
17030835
J Biol Chem. 1997 Oct 10;272(41):25576-82
9325276
Proteomics. 2008 Apr;8(7):1516-27
18383005
Mol Cell Proteomics. 2002 Nov;1(11):845-67
12488461
Proteomics. 2001 Dec;1(12):1503-6
11747208
Lancet. 1999 May 15;353(9165):1649-52
10335783
Diabetes. 2005 Feb;54(2):570-5
15677517
J Proteome Res. 2002 Jul-Aug;1(4):375-80
12645894
Science. 1989 Jun 23;244(4911):1483-7
2734615
Autoimmunity. 2003 May;36(3):177-81
12911285
Metabolism. 2002 Jul;51(7):838-42
12077727
Proteomics. 2004 Jan;4(1):244-56
14730686
Biochemistry. 1994 Mar 1;33(8):1988-93
8117655
Diabetes. 2002 May;51(5):1596-600
11978661
Nature. 1997 Apr 3;386(6624):506-10
9087411
Rev Inst Med Trop Sao Paulo. 1994 Sep-Oct;36(5):479
7569618
Diab Vasc Dis Res. 2005 May;2(2):54-60
16305059
Med Hypotheses. 2008;70(2):424-9
17553627
Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10852-7
16043703
Diabetes Res Clin Pract. 2004 Oct;66(1):41-7
15364160
J Biol Chem. 1996 Jan 19;271(3):1776-83
8576182
J Lipid Res. 1988 Mar;29(3):273-8
3379339
Atherosclerosis. 2003 Apr;167(2):257-64
12818408
Proteomics. 2005 Aug;5(13):3442-53
16047309
Ann Fam Med. 2005 Jan-Feb;3(1):60-3
15671192
Horm Metab Res. 2005 Apr;37 Suppl 1:95-8
15918118
J Biol Chem. 1999 Oct 29;274(44):31286-90
10531326
Mol Cell Proteomics. 2003 Jun;2(6):399-404
12851465
Proteomics. 2006 Jan;6(2):721-30
16419016
Curr Opin Lipidol. 2004 Jun;15(3):261-7
15166781
J Lipid Res. 2004 Jun;45(6):993-1007
15060092
Med Hypotheses. 2007;69(6):1272-6
17553629
Diabetologia. 1997 Nov;40(11):1286-92
9389420
Proc Natl Acad Sci U S A. 1984 Mar;81(5):1356-60
6424116
Immunobiology. 1998 Aug;199(2):348-57
9777418
Mol Genet Metab. 2008 Apr;93(4):481-4
18055244
Metabolism. 1989 Nov;38(11):1042-6
2478861
Proteomics. 2005 Apr;5(5):1431-45
15761960
Arch Intern Med. 2003 Jan 13;163(1):93-9
12523922
Semin Liver Dis. 1997;17(4):297-310
9408965
J Lipid Res. 2003 Jul;44(7):1387-94
12700345
Altern Med Rev. 2001 Jun;6(3):248-71
11410071
Clin Chem. 2005 Feb;51(2):351-9
15528295
Clin Immunol. 2008 Jun;127(3):394-400
18533284
Circ J. 2007 Jun;71(6):868-73
17526982
Diabetes. 2002 Apr;51(4):1131-7
11916936
Free Radic Biol Med. 2007 Sep 1;43(5):730-9
17664137
Atherosclerosis. 1994 Jan;105(1):25-34
8155085
Diabetes Metab. 2003 Sep;29(4 Pt 2):6S9-18
14502096
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
10592173
Immunol Today. 1995 Feb;16(2):58-61
7888067
JAMA. 2001 Jul 18;286(3):327-34
11466099
J Am Coll Cardiol. 2007 May 1;49(17):1798-805
17466231
J Clin Invest. 2007 Mar;117(3):746-56
17332893