Sitole Lungile, Steffens Francois, Krüger Tjaart P J, Meyer Debra
1 Department of Biochemistry, University of Pretoria , Pretoria, South Africa .
OMICS. 2014 Aug;18(8):513-23. doi: 10.1089/omi.2013.0157. Epub 2014 Jun 17.
Global health, whether in developed or developing countries, is in need of robust systems diagnostics for major diseases, such as HIV/AIDS, impacting the world populations. Fourier transform Infrared (FTIR) spectroscopy of serum is a quick and reagent-free methodology with which to analyze metabolic alterations such as those caused by disease or treatment. In this study, Attenuated Total Reflectance Fourier-Transform (ATR-FTIR) Spectroscopy was investigated as a means of distinguishing HIV-infected treatment-experienced (HIV(pos) ART(pos), n=39) and HIV-infected-treatment-naïve (HIV(pos) ART(neg), n=16) subjects from uninfected control subjects (n=30). Multivariate pattern recognition techniques, including partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), successfully distinguished sample classes, while univariate approaches identified significant differences (p<0.05) after Benjamini-Hochberg corrections. OPLS-DA discriminated between all groups with sensitivity, specificity, and accuracy of >90%. Compared to uninfected controls, HIV(pos) ART(pos) and HIV(pos) ART(neg) subjects displayed significant differences in spectral regions linked to lipids/fatty acids (3010 cm(-1)), carbohydrates (1299 cm(-1); 1498 cm(-1)), glucose (1035 cm(-1)), and proteins (1600 cm(-1); 1652 cm(-1)). These are all molecules shown by conventional biochemical analysis to be affected by HIV/ART interference. The biofluid metabolomics approach applied here successfully differentiated global metabolic profiles of HIV-infected patients and uninfected controls and detected potential biomarkers for development into indicators of host response to treatment and/or disease progression. Our findings therefore contribute to ongoing efforts for capacity-building in global health for robust omics science and systems diagnostics towards major diseases impacting population health.
全球健康,无论在发达国家还是发展中国家,都需要针对影响世界人口的重大疾病(如艾滋病毒/艾滋病)建立强大的系统诊断方法。血清的傅里叶变换红外(FTIR)光谱分析是一种快速且无需试剂的方法,可用于分析由疾病或治疗引起的代谢变化。在本研究中,衰减全反射傅里叶变换(ATR-FTIR)光谱分析被用作一种区分受艾滋病毒感染且有治疗经历(HIV(pos) ART(pos),n = 39)、受艾滋病毒感染且未接受过治疗(HIV(pos) ART(neg),n = 16)的受试者与未感染对照受试者(n = 30)的手段。多元模式识别技术,包括偏最小二乘判别分析(PLS-DA)和正交偏最小二乘判别分析(OPLS-DA),成功区分了样本类别,而单变量方法在进行Benjamini-Hochberg校正后确定了显著差异(p<0.05)。OPLS-DA对所有组的区分具有>90%的敏感性、特异性和准确性。与未感染对照相比,HIV(pos) ART(pos)和HIV(pos) ART(neg)受试者在与脂质/脂肪酸(3010 cm(-1))、碳水化合物(1299 cm(-1);1498 cm(-1))、葡萄糖(1035 cm(-1))和蛋白质(1600 cm(-1);1652 cm(-1))相关的光谱区域显示出显著差异。这些都是传统生化分析表明受艾滋病毒/抗逆转录病毒治疗干扰影响的分子。此处应用的生物流体代谢组学方法成功区分了艾滋病毒感染患者和未感染对照的整体代谢谱,并检测到了潜在的生物标志物,有望发展成为宿主对治疗和/或疾病进展反应的指标。因此,我们的研究结果有助于全球健康领域正在进行的能力建设努力,以推动针对影响人群健康的重大疾病的强大组学科学和系统诊断。