多批次肝衰竭患者呼出气体的电喷雾萃取电离质谱检测及代谢组学数据分析

doi:10.7503/cjcu20150826

摘要/Abstract

摘要：

采用高分辨电喷雾萃取电离质谱(EESI-MS)技术对肝衰竭患者和健康志愿者呼出气体样本进行快速检测, 结合多块偏最小二乘分析(MB-PLS)方法, 对多批次获取的呼出气体代谢数据进行统计建模分析, 并与传统的PLS方法进行比较. 结果表明, MB-PLS方法能有效消除批次差异对统计建模的影响. 此外, 利用MB-PLS模型变量VIP值对变量进行筛选, 可降低数据的冗余, 消除无关变量对模型的影响, 从而有效提高了模型的性能.

关键词: 呼出气体, 代谢组学, 电喷雾萃取电离质谱, 多块偏最小二乘分析

Abstract:

In metabolomics studies, the number of samples should be enough to guarantee the reliability of data statistical analysis. The effective storage time of exhaled breath is short, and it is difficult to collect and detect a large number of breath samples in a short time. Combining multi batches of samples may obtain a large data, but usually there is a large variance between batches induced by ambient air varying. In this paper, the exhaled breath data of liver failure patients and healthy volunteers were obtained by high resolution extractive electrospray ionization mass spectrometry(EESI-MS) and then analyzed by multi-block partial least square(MB-PLS). The results were compared with traditional PLS method and showed its strength of removing the variance of batches for modeling. Moreover, we provided a variable selection strategy that based on variable importance in the projection(VIP) of MB-PLS to reduce the redundancy of data and eliminate the effect of non-information variables for modeling, and the performance of MB-PLS model had a great improvement.

Key words: Exhaled breath, Metabolomics, Extractive electrospray ionization mass spectrometry, Multi-block partial least square analysis

中图分类号:

O657.6

TrendMD:

李鹏辉, 邓伶莉, 罗娇, 李巍, 宁晶, 丁健桦, 邬小萍. 多批次肝衰竭患者呼出气体的电喷雾萃取电离质谱检测及代谢组学数据分析. 高等学校化学学报, 2016, 37(4): 626.

LI Penghui, DENG Lingli, LUO Jiao, LI Wei, NING Jing, DING Jianhua, WU Xiaoping. EESI-MS Detection and Statistical Analysis of Multi-batch of Exhaled Breath Metabolomics Data of Liver Failure Patients. Chem. J. Chinese Universities, 2016, 37(4): 626.

图/表 8

Fig.1 Two typical multi-block problems(A) The objects are in common, but the variables measured on these objects are different; (B) the variables are in common, but the objects are different.

Table 1 Four batches of exhaled breath sample

Batch	Date of collection	Liver failure patient	Healthy volunteer	Batch	Date of collection	Liver failure patient	Healthy volunteer
1	2014-07-08	9	4	3	2014-08-25	8	11
2	2014-08-14	9	4	4	2014-09-11	9	16

Fig.2 EESI-MS spectra of exhaled breath from liver failure patients and healthy volunteers (A)—(D) MS data of exhaled breath from liver failure patients; (E)—(H) MS data of exhaled breath from healthy volunteers. Each row represents a batch.

Fig.3 Scores plot of MB-PLS model(A) and PLS model(B) by the four batches of data respectivelyThe batches labeled by different graphics, the hollow red graphics and solid blue graphics for the disease group and control group respectively.

Fig.4 Model validation results of MB-PLS(○) and PLS(△) respectively

Fig.5 VIP scores of MB-PLS model

Fig.6 Variation of the mean CAMCCV of MB-PLS model with the threshold of VIP

Fig.7 MS/MS spectrum and proposed structure of m/z 90 from the data of liver failure patients and healthy volunteers breath samples

参考文献 39

[1]	Phillips M., Herrera J., Krishnan S., Zain M., Greenberg J., Cataneo R. N., J. Chromatogr. B, 1999, 729(1/2), 75—88
[2]	Gieger C., Geistlinger L., Altmaier E., de Angelis M. H., Kronenberg F., Meitinger T., Mewes H. W., Wichmann H. E., Weinberger K. M., Adamski J., Illig T., Suhre K., Plos Genet., 2008, 4(11), e1000282
[3]	Want E. J., Wilson I. D., Gika H., Theodoridis G., Plumb R. S., Shockcor J., Holmes E., Nicholson J. K., Nat.Protoc., 2010, 5(6), 1005—1018
[4]	Sugimoto M., Wong D. T., Hirayama A., Soga T., Tomita M., Metabolomics, 2010, 6(1), 78—95
[5]	Yuan M., Breitkopf S. B., Yang X. M., Asara J. M., Nat. Protoc., 2012, 7(5), 872—881
[6]	Carraro S., Rezzi S., Reniero F., Héberger K., Giordano G., Zanconato S., Guillou C., Baraldi E., Am. J. Respir. Crit. Care. Med., 2007, 175(10), 986—990
[7]	Motta A., Paris D., Melck D., de Laurentiis G., Maniscalco M., Sofia M., Montuschi P., Eur. Respir. J., 2012, 39(2), 498—500
[8]	Gu H. W., Qi Y. P., Xu N., Ding J. H., An Y. B., Chen H. W., Chinese J. Anal. Chem., 2012, 40(12), 1933—1937
	(顾海威, 齐云鹏, 许宁, 丁健桦, 安艳波, 陈焕文. 分析化学, 2012, 40(12), 1933—1937 )
[9]	Chen C., Deng L. L., Wei S. W., Gowda G. A. N., Gu H. W., Chiorean E. G., Abu Zaid M., Harrison M. L., Pekny J. F., Loehrer P. J., J. Proteome Res., 2015, 14(6), 2492—2499
[10]	Gu H. W., Huang Y., Filgueira M., Carr P. W., J. Chromatogr. A, 2011, 1218(38), 6675—6687
[11]	Hanouneh I. A., Zein N. N., Cikach F., Dababneh L., Grove D., Alkhouri N., Lopez R., Dweik R. A., Clin. Gastroenterol.H., 2014, 12(3), 516—523
[12]	Van Den Velde S., Nevens F., Van Hee P., Van Steenberghe D., Quirynen M., J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 2008, 875(2), 344—348
[13]	Krotoszynski B., Gabriel G., Oneill H., Claudio M. P. A., J. Chromatogr. Sci., 1977, 15(7), 239—244
[14]	Phillips M., Gleeson K., Hughes J. M. B., Greenberg J., Cataneo R. N., Baker L., McVay W. P., Lancet, 1999, 353(9168), 1930—1933
[15]	Netzer M., Millonig G., Osl M., Pfeifer B., Praun S., Villinger J., Vogel W., Baumgartner C., Bioinformatics, 2009, 25(7), 941—947
[16]	Casalinuovo I. A., Di Pierro D., Coletta M., Di Francesco P., Sensors, 2006, 6(11), 1428—1439
[17]	Roeck F., Barsan N., Weimar U., Chem. Rev., 2008, 108(2), 705—725
[18]	Skeldon K. D., Mcmillan L. C., Wyse C. A., Monk S. D., Gibson G., Patterson C., France T., Longbottom C., Padgett M. J., Respir. Med., 2006, 100(2), 300—306
[19]	Storer M., Dummer J., Sturney S., Epton M., Curr. Anal. Chem., 2013, 9(4), 576—583
[20]	Moser B., Bodrogi F., Eibl G., Lechner M., Rieder J., Lirk P., Resp. Physiol. Neurobi., 2005, 145(2/3), 295—300
[21]	Pan S. S., Zhao N., Ouyang Y. Z., Huang K. K., Ding J. H., Chen H. W., Yuan L., Wang X. X., Chem. J. Chinese Universities, 2013, 34(6), 1379—1384
	(潘素素, 赵娜, 欧阳永中, 黄科科, 丁健桦, 陈焕文, 袁龙, 王兴祥. 高等学校化学学报, 2013, 34(6), 1379—1384 )
[22]	Ding J. H., Wang X. X., Zhang H., Pan S. S., Luo M. B., Li J. Q., Chen H. W., Chem. J. Chinese Universities, 2011, 32(8), 1714—1719
	(丁健桦, 王兴祥, 张慧, 潘素素, 罗明标, 李建强, 陈焕文. 高等学校化学学报, 2011, 32(8), 1714—1719)
[23]	Chen H. W., Wortmann A., Zhang W. H., Zenobi R., Angew. Chem. Int. Ed., 2007, 46(46), 580—583
[24]	Pan S. S., Tian Y., Li M., Zhao J. Y., Zhu L. L., Zhang W., Gu H. W., Wang H. D., Shi J. B., Fang X., Li P. H., Chen H. W., Sci. Rep., 2015, 5,8725
25	[25] Ding J.H., Yang S. P., Liang D. P., Chen H. W., Wu Z. Z., Zhang L. L., Ren Y. L., Analyst, 2009, 134(10), 2040—2050
[26]	Wood C. C., Mccarthy G., Electroencephalogr. Clin. Neurophysiol., 1984, 59(3), 249—260
[27]	Frank I. E., Kowalski B. R., Anal. Chim. Acta, 1984, 162, 241—251
[28]	Wang W. X., Zhou H. H., Lin H., Roy S., Shaler T. A., Hill L. R., Norton S., Kumar P., Anderle M., Becker C. H., Anal. Chem., 2003, 75(18), 4818—4826
[29]	Redestig H., Fukushima A., Stenlund H., Moritz T., Arita M., Saito K., Kusano M., Anal. Chem., 2009, 81(19), 7974—7960
[30]	Jauhiainen A., Basetti M., Narita M., Narita M., Griffiths J., Tavare' S., BMC Bioinformatics, 2014, 30(15), 2155—2161
[31]	De Livera A. M., Dias D. A., De Souza D., Rupasinghe T., Pyke J., Tull D., Roessner U., McConville M., Speed T. P., Anal. Chem., 2012, 84(24), 10768—10776
[32]	Wangen L. E., Kowalski B. R., J. Chemometr., 1989, 3(1), 3—20
[33]	Beauchamp J., Herbig J., Gutmann R., Hansel A., J. Breath Res., 2008, 2(4), 046001
[34]	Picard R. R., Cook R. D., J. Am. Stat. Assoc., 1984, 79(387), 575—583
[35]	Lindgren F., Hansen B., Karcher W., Sjostrom M., Eriksson L., J. Chemometr., 1996, 10(5/6), 521—532
[36]	Levine M., Tarver H., J. Biol. Chem., 1950, 184(2), 427—436
[37]	Pilgeram L. O., Gal E. M., Sassenrath E. N., Greenberg D. M., J. Biol. Chem., 1953, 204(1), 367—377
[38]	Duvigneaud V., Chandler J. P., Simmonds S., Moyer A. W., Cohn M., J. Biol. Chem., 1946, 164(2), 603—613
[39]	Artom C., Crowder M., Fed. Proc., 1949, 8(1), 180—181