Probing latent biomarker signatures and in vivo pathway activity in experimental disease states via statistical total correlation spectroscopy (STOCSY) of biofluids:: Application to HgCl2 toxicity

被引:81
作者
Holmes, E. [1 ]
Cloarec, O. [1 ]
Nicholson, J. K. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, London SW7 2AZ, England
基金
英国惠康基金;
关键词
metabonomics; STOCSY; NMR; Hg2+; renal cortical toxicity; biomarker signature;
D O I
10.1021/pr050399w
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A new multivariate statistical approach, based on the novel combination of projection on latent structure analysis with an inbuilt orthogonal filter (OPLS-DA) coupled with a spectroscopic correlation method statistical total correlation spectroscopy (STOCSY), was used to characterize the in vivo metabolic pathway perturbations of a model renal cortical toxin HgCl2, in the rat, using urine as an indicator of metabolic homeostasis disruption. This method provided an unbiased, sensitive approach to biomarker extraction and identification, and showed potential for generating potential novel pathway connectivities.
引用
收藏
页码:1313 / 1320
页数:8
相关论文
共 43 条
[1]   Human renal organic anion transporter 1-dependent uptake and toxicity of mercuric-thiol conjugates in Madin-Darby canine kidney cells [J].
Aslamkhan, AG ;
Han, YH ;
Yang, XP ;
Zalups, RK ;
Pritchard, JB .
MOLECULAR PHARMACOLOGY, 2003, 63 (03) :590-596
[2]  
Bairaktari E, 2002, CLIN CHEM, V48, P1106
[3]   STUDIES ON THE PATHO-PHYSIOLOGY OF ACUTE-RENAL-FAILURE .4. PROTECTIVE EFFECT OF DITHIOTHREITOL FOLLOWING ADMINISTRATION OF MERCURIC-CHLORIDE IN THE RAT [J].
BARNES, JL ;
MCDOWELL, EM ;
MCNEIL, JS ;
FLAMENBAUM, W ;
TRUMP, BF .
VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY, 1980, 32 (03) :201-232
[4]  
BARRETT GC, 1998, AMINO ACIDS PEPTIDES, P1
[5]   Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins [J].
Beckwith-Hall, BM ;
Nicholson, JK ;
Nicholls, AW ;
Foxall, PJD ;
Lindon, JC ;
Connor, SC ;
Abdi, M ;
Connelly, J ;
Holmes, E .
CHEMICAL RESEARCH IN TOXICOLOGY, 1998, 11 (04) :260-272
[6]  
BOTI Z, 1981, EXP PATHOL-JENA, V19, P247
[7]  
Brindle JT, 2002, NAT MED, V8, P1439, DOI 10.1038/nm802
[8]   Structure of renal organic anion and cation transporters [J].
Burckhardt, G ;
Wolff, NA .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2000, 278 (06) :F853-F866
[9]   AN INVESTIGATION OF ARGININOSUCCINIC ACID ANHYDRIDES IN ARGININOSUCCINIC ACID LYASE DEFICIENCY BY H-1-NMR SPECTROSCOPY [J].
BURNS, SP ;
ILES, RA .
CLINICA CHIMICA ACTA, 1993, 221 (1-2) :1-13
[10]   Statistical total correlation spectroscopy:: An exploratory approach for latent biomarker identification from metabolic 1H NMR data sets [J].
Cloarec, O ;
Dumas, ME ;
Craig, A ;
Barton, RH ;
Trygg, J ;
Hudson, J ;
Blancher, C ;
Gauguier, D ;
Lindon, JC ;
Holmes, E ;
Nicholson, J .
ANALYTICAL CHEMISTRY, 2005, 77 (05) :1282-1289