Applying computation biology and “big data” to develop multiplex diagnostics for complex chronic diseases such as osteoarthritis

Figures & data

Table 1. Biomarker approaches examined for the diagnosis of osteoarthritis.

Publication name	Publish date	Biochemical biomarkers	Body fluid	Sample size	Age	Gender	Comparison group	Statistical method	Sensitivity/ specificity
Role of hyaluronic acid in early diagnosis of knee osteoarthritis (Singh et al., 2014a)	2014.12	Hyaluronic acid	Serum	100/50 (cases/controls)	Case 51.28 ± 7.93 Control 46.08 ± 4.81 p<0.001	Case: 34 males, 66 females; Control: 16 males 34 females	Normal/mild OA	ROC curve	87.6%/86.0%
Identification and characterization of osteoarthritis patients with inflammation derived tissue turnover (Siebuhr et al., 2014)	2014.1	hsCRP, CRPM	Serum	12/202/57/60 (mild/moderate/ severe/TKR)	Mean: 65.3	155 Males;176 females	Mild/moderate/ severe/TKR	ROC curve	33.3%/87.18%
TSG-6 activity as a novel biomarker of progression in knee osteoarthritis (Wisniewski et al., 2014)	2014.2	TSG-6	Synovial fluid, serum	91 (OA)			High/low risk of rapid progression to end-stage OA	ROC curve	91%/82%
A computational method to differentiate normal individuals, osteoarthritis and rheumatoid arthritis patients using serum biomarkers (Heard et al., 2014)	2014.6	38 cytokines	Serum	100/100 (cases/controls)	Normal: 40.0 ± 9.5 OA: 60.4 ± 10		Normal/OA	Artificial neural network	100%/100%
Serum Cartilage Oligomeric Matrix Protein: tool for early diagnosis and grading of severity of primary knee osteoarthritis (Singh et al., 2014b)	2014.8	COMP	Serum	100/50 (cases/controls)	Cases: 58.93 ± 9.20 Control: 54.68 ± 9.68	50 Males;100 females	Normal/OA (KL = 0/KL ≥ 1)	ROC curve	98%/98%
Usefulness of urinary CTX-II and NTX-I in evaluating radiological knee osteoarthritis: the Matsudai knee osteoarthritis survey (Tanishi et al., 2014)	2014.2	uCTX-II	Urine	794/616 (OA/normal)	Males:KL0: 1:65.3 ± 9.7 KL2: 72.3 ± 5.3 KL3: 72.5 ± 4.9 KL4: 74.7 ± 3.2FemalesKL0,: 1. 60.7 ± 9.5KL2: 70.3 ± 6.0KL3: 71.6 ± 6.1KL4: 72.9 ± 5.1	435 Males;605 females	KL0, 1/KL ≥ 2	ROC curve	≈60%/40% men ≈70%40 women
Cartilage Oligomeric Matrix Protein – inflammation biomarker in knee osteoarthritis (Zivanovic et al., 2011)	2011.2	COMP	Serum	66/22 (effusion/control)	69.97 ± 9.37	20 Males;68 females	With/without effusion (inflammation)	ROC Curve	59%/50%
Identification of Osteoarthritis Biomarkers by Proteomic Analysis of Synovial Fluid (Han et al., 2012)	2012.12	S100A12 and other two unknown proteins	Synovial fluid	36/24 (OA/RA)	OA: 70.2 ± 5.4RA: 68.4 ± 4.9	OA: 9 males, 27 femalesRA: 4 males, 20 females	OA/RA	Artificial neural network	89.4%/ 91.2%
Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis (Henrotin et al., 2012)	2012.07	Fib3-1, Fib3-2	Urine	10/5 (cases/controls)	Cases: 76.0 ± 5.0 Control: 25.6 ± 2.6	15 Females	Normal/late OA	ROC curve	Fib3-1: 68.4%/ 77.1%, Fib3-2: 74.6%/ 85.7

Singh S, Kumar D, Sharma NR. (2014a). Role of hyaluronic acid in early diagnosis of knee osteoarthritis. J Clin Diagn Res 8:LC04–7

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Siebuhr AS, Petersen KK, Arendt-Nielsen L, et al. (2014). Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. Osteoarthritis Cartilage 22:44–50

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Wisniewski HG, Colon E, Liublinska V, et al. (2014). TSG-6 activity as a novel biomarker of progression in knee osteoarthritis. Osteoarthritis Cartilage 22:235–41

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Heard BJ, Rosvold JM, Fritzler MJ, et al. (2014). A computational method to differentiate normal individuals, osteoarthritis and rheumatoid arthritis patients using serum biomarkers. J R Soc Interface 11:20140428

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Singh S, Shahi U, Kumar D, Shahi NT. (2014b). Serum Cartilage Oligomeric Matrix Protein: tool for early diagnosis and grading of severity of primary knee osteoarthritis. Int J Osteol Orthop 1:1–7

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Tanishi N, Yamagiwa H, Hayami T, et al. (2014). Usefulness of urinary CTX-II and NTX-I in evaluating radiological knee osteoarthritis: the Matsudai knee osteoarthritis survey. J Orthop Sci 19:429–36

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Zivanovic S, Rackov LP, Zivanovic A, et al. (2011). Cartilage oligomeric matrix protein-inflammation biomarker in knee osteoarthritis. Bosn J Basic Med Sci 11:27–32

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Han MY, Dai JJ, Zhang Y, et al. (2012). Identification of osteoarthritis biomarkers by proteomic analysis of synovial fluid. J Int Med Res 40:2243–50

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Henrotin Y, Gharbi M, Mazzucchelli G, et al. (2012). Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis. Arthritis Rheum 64:2260–7

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