Potential biomarkers for early detection of acute graft-versus-host disease

Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HCT), resulting in considerable morbidity and mortality. Currently, the diagnosis of aGVHD is largely made based on clinical parameters and invasive biopsies. For the past 20 years, researchers have been trying to find reliable biomarkers to enable early and accurate diagnosis of aGVHD. Although a number of potential aGVHD biomarkers have been published, as yet, no validated diagnostic test is available. Proteomics encompasses a broad range of rapidly developing technologies, which have shown tremendous promise for early detection of aGVHD. In this article, we review the current state of aGVHD biomarker discovery, provide a summary of the key proteins of interest and the most common analytical procedures for the clinic, as well as outlining the significant challenges faced in their use.     

Formalin-fixed paraffin-embedded tissue: The holy grail of clinical proteomics?

Tissue is the most relevant biological material to gather insight in disease mechanisms by means of omics technologies. However, fresh frozen tissue, which is generally regarded as the best imaginable source for such studies, is often not available. In case it is available, the different ways of storage (e.g. −20°C, −80°C, liquid nitrogen, etc.) hamper the conduction of reproducible multicenter studies because of different protein degradation rates. Formalin-fixed paraffin-embedded (FFPE) tissue on the contrary is considered as a valuable alternative for fresh frozen tissue, because only a few standard operation procedures are applied worldwide for the preparation of these tissues and because they are all stored in the same way. However, a study on the impact of the different preparation protocols for FFPE tissue was still lacking. Therefore, Bronsert et al. in this issue [Bronsert, P., Weißer, J., Biniossek, M. L., Kuehs, M. et al., Proteomics Clin. Appl. 2014, 8 786–804] conducted such a study that provides proof that there is no significant effect between these sample preparations procedures, and thereby they further open the gate for FFPE tissues to enter the field of clinical proteomics.     

Exploring the potential of platelet proteomics in children

Proteomics is a rapidly evolving ‘‘post-genomic’’ science utilizing advanced technologies in protein separation, identification, quantitation and heavily relying on bioinformatics. Proteomic research in pediatrics is important and most of the successes thus far are seen in research that utilize samples that require less invasive procedures and focus on prevailing childhood diseases such as acute lymphoblastic leukaemia and neuroblastoma. Recent advances in proteomics are helping to elucidate platelet processes that are relevant to bleeding and clotting disorders, as well as other important roles of platelets such as in angiogenesis and inflammation. Nevertheless, most of platelet proteome data obtained to date are derived from the adult population and the potential of platelet proteomic application in children has not yet been explored. As it happens in all research fields, there are additional challenges in studying children such as procuring sufficient biological samples and access to less common disease cohorts as compared to in adults. Furthermore, many of the prevalent platelet-mediated diseases in adults, such as coronary heart disease and atherosclerotic lesions, are believed to have origins during childhood. Hence, platelet proteomic research in children may reveal some important information on how platelet plays a role in the pathogenesis of disease. In this article, we refer to the current knowledge from platelet proteomic research strategies in adults and address the specific concerns in the study of pediatric samples.     

House dust induces IL-6 and IL-8 response in A549 epithelial cells

The in vitro potency of house dust to induce cytokine response in A549 lung epithelial cells was studied. Dusts collected from carpet, bed, shelf and floor of a villa and an apartment by vacuuming were found to trigger the production of interleukin-8 (IL-8) and interleukin-6 (IL-6) in a dose-dependent manner, and the interleukin production was several-fold higher than of swine dust (used as a positive control). The IL-8 and IL-6 production of pure Escherichia coli lipopolysaccharide was significantly lower than of the dusts and a peptidoglycan-polysaccharide complex did not show any stimulatory effect at all. The lipopolysaccharide and peptidoglycan contents of the samples were determined by gas chromatography-tandem mass spectrometry analysis of, respectively, 3-hydroxy fatty acids and muramic acid; in addition, ergosterol was monitored for fungal biomass. The inflammatory properties of house dust upon inhalation may be reflected in its high potency to induce cytokine response in lung epithelial cells.     

Two simple algorithms on linear combination of multiple biomarkers to maximize partial area under the ROC curve

In clinical practices, it is common that several biomakers are related to a specific disease and each single marker does not have enough diagnostic power. An effective way to improve the diagnostic accuracy is to combine multiple markers. It is known that the area under the receiver operating characteristic curve (AUC) is very popular for evaluation of a diagnostic tool. Su and Liu (1993) derived the best linear combination that maximizes AUC when the markers are multivariate normally distributed. However, there are many applications that do not operate in the entire range of the curve, but only in particular regions of it, for example, high specificity regions. In these cases, it is more practical to analyze the partial area under the curve (pAUC). In this paper, we propose two easy-implemented algorithms, to find the best linear combination of multiple biomarkers that optimizes the pAUC, for given range of specificity. Analysis of synthesized and real datasets shows that the proposed algorithms achieve larger predictive pAUC values on future observations than existing methods, such as Su and Liu’s method, logistic regression and others.     

Antioxidant profile of red-single variety wines microoxygenated before malolactic fermentation

The controlled addition of oxygen before malolactic fermentation involves stability of wine colour and an improvement in their organoleptic quality. This study has examined its effect on the “in vitro” antioxidant profile of a variety of Spanish red-single variety wines of different ages. Total antioxidant capacity scavenger activity and the biomarkers of oxidative stress were all analysed. Neither antioxidant capacity, nor scavenger activity were influenced by the microoxygenation. However, the biomarkers of oxidative stress showed some effect of this technique. The controlled addition of small amounts of oxygen produced an increase in the prevention of DNA-damage and seems to decrease the capacity to inhibit lipid peroxidation. The effect on the capacity to protect DNA-damages was statistically significant in the groups of young and one year old wines, where microoxygenated wines showed higher values than their respective control ones. Furthermore, the effect on the prevention of lipid peroxidation was only qualitative, any statistical significant difference was found. A varietal effect was observed in analyzing the results, being Tinta del País wines the most influenced by this technique.     

Compositional Changes of Hydrocarbons of Residual Oil in Contaminated Soil During Ozonation

Ozonation is an effective method to remove recalcitrant weathered oil in contaminated soil. The purpose of this study was to characterize the compositional changes of hydrocarbons in residual oil during ozonation. A bioremediated soil containing residual oil was ozonated for up to 15 h. A total of 102 compounds in the residual oil were analyzed by GC/MS and 36 diagnostic ratios (DRs) were calculated based on quantitative or semi-quantitative results in order to evaluate the susceptibility of the residual oil compositions to ozonation and the effects of ozonation on the fingerprint profile of the residual oil. The total ozonation removal rates were in the following order: triaromatic steranes (TAS) > steranes, polycyclic aromatic hydrocarbons, terpanes > alkanes. Ozone kept the fingerprints of n-alkanes, C₂₇- to C₃₄-terpanes, steranes and TAS, separately. Branched alkanes (i.e., pristane and phytane) showed a higher removal rate than n-alkanes. Ozone reactivity of PAHs depended on the number of rings, presence of heteroatoms and level of alkylation. Four- to six-ring PAHs and PAHs with a high level of alkylation showed higher reactivity, while dibenzothiophene and alkylated dibenzothiophenes were found to be resistant to ozonation. Some of the biomarker source ratios remained stable and could still be used for source identification even after some of the biomarkers were removed by >90% by ozonation.