Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are characterized by airway obstruction and an inflammatory process. Reaching early diagnosis and discrimination of subtypes of these respiratory diseases are quite a challenging task than other chronic illnesses. Metabolomics is the study of metabolic pathways and the measurement of unique biochemical molecules generated in a living system. In the last decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. In this article, we review the current state of the metabolomics of COPD, asthma and CF with a focus on the different methods and instrumentation being used for the discovery of biomarkers in research and translation into clinic as diagnostic aids for the choice of patient-specific therapies.

Chronic Kidney Disease (CKD) is a global health problem annually affecting millions of people around the world. It is a comprehensive syndrome, and various factors may contribute to its occurrence. In this study, it was attempted to provide an accurate definition of chronic kidney disease; followed by focusing and discussing on molecular pathogenesis, novel diagnosis approaches based on biomarkers, recent effective antigens and new therapeutic procedures related to high-risk chronic kidney disease such as membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy, which may lead to end-stage renal diseases. Additionally, a considerable number of metabolites and proteins that have previously been discovered and recommended as potential biomarkers of various CKDs using ‘-omics-’ technologies, proteomics, and metabolomics were reviewed.

Metabolomics methods have been widely used in the field of biomarker discovery in TC and attempts are still in progress to use these methods to find a reliable biomarker panel besides current diagnostic tools.

Membranous glomerulonephritis (MGN) is one of the most frequent causes of nephrotic syndrome in adults. It is characterized by the thickening of the glomerular basement membrane in the renal tissue. The current diagnosis of MGN is based on renal biopsy and the detection of antibodies to the few podocyte antigens. Due to the limitations of the current diagnostic methods, including invasiveness and the lack of sensitivity of the current biomarkers, there is a requirement to identify more applicable biomarkers. The present study aimed to identify diagnostic metabolites that are involved in the development of the disease using topological features in the component-reaction-enzyme-gene (CREG) network for MGN. Significant differential metabolites in MGN compared with healthy controls were identified using proton nuclear magnetic resonance and gas chromatography-mass spectrometry techniques, and multivariate analysis. The CREG network for MGN was constructed, and metabolites with a high centrality and a striking fold-change in patients, compared with healthy controls, were introduced as putative diagnostic biomarkers. In addition, a protein-protein interaction (PPI) network, which was based on proteins associated with MGN, was built and analyzed using PPI analysis methods, including molecular complex detection and ClueGene Ontology. A total of 26 metabolites were identified as hub nodes in the CREG network, 13 of which had salient centrality and fold-changes: Dopamine, carnosine, fumarate, nicotinamide D-ribonucleotide, adenosine monophosphate, pyridoxal, deoxyguanosine triphosphate, L-citrulline, nicotinamide, phenylalanine, deoxyuridine, tryptamine and succinate. A total of 13 subnetworks were identified using PPI analysis. In total, two of the clusters contained seed proteins (phenylalanine-4-hydroxlylase and cystathionine γ-lyase) that were associated with MGN based on the CREG network. The following biological processes associated with MGN were identified using gene ontology analysis: ‘Pyrimidine-containing compound biosynthetic process’, ‘purine ribonucleoside metabolic process’, ‘nucleoside catabolic process’, ‘ribonucleoside metabolic process’ and ‘aromatic amino acid family metabolic process’. The results of the present study may be helpful in the diagnostic and therapeutic procedures of MGN. However, validation is required in the future.

The present study was designed to search for metabolic biomarkers and their correlation with serum zinc in Crohn's disease patients. Crohn's disease (CD) is a form of inflammatory bowel disease that may affect any part of the gastrointestinal tract and can be difficult to diagnose using the clinical tests. Thus, introduction of a novel diagnostic method would be a major step towards CD treatment. Proton nuclear magnetic resonance spectroscopy ((1)H NMR) was employed for metabolic profiling to find out which metabolites in the serum have meaningful significance in the diagnosis of CD. CD and healthy subjects were correctly classified using random forest methodology. The classification model for the external test set showed a 94% correct classification of CD and healthy subjects. The present study suggests Valine and Isoleucine as differentiating metabolites for CD diagnosis. These metabolites can be used for screening of risky samples at the early stages of CD diagnoses. Moreover, a robust random forest regression model with good prediction outcomes was developed for correlating serum zinc level and metabolite concentrations. The regression model showed the correlation (R(2)) and root mean square error values of 0.83 and 6.44, respectively. This model suggests valuable clues for understanding the mechanism of zinc deficiency in CD patients.

BackgroundCeliac disease (CD) is a disorder associated with body reaction to gluten. After the gluten intake, an immune reaction against the protein occurs and damages villi of small intestine in celiac patients gradually.ObjectivesThe OSC, a filtering method for minimization of inter- and intra-spectrometer variations that influence on data acquisition, was applied to biofluid NMR data of CD patients.Patients and MethodsIn this study, metabolites of total 56 serum samples from 12 CD patients, 15 CD patients taking gluten-free diet (GFD), and 29 healthy cases were analyzed using nuclear magnetic resonance (NMR) and associated theoretical analysis. Employing ProMetab (version ProMetab_v3_3) software, data obtained from NMR spectra were reduced and orthogonal signal correction (OSC) effect on celiac disease metabonomics before and after the separation by principle component analysis (PCA) was investigated.ResultsThe three groups were separated by OSC and findings were analyzed by partial least squares discriminant analysis (PLS-DA) method. Root mean square error of calibration (RMSEc) and correlation coefficient of calibration (Rc) for PLS-DA referred to an efficient group separation filtered by OSC.ConclusionsThe applied leave-one-out cross-validation to PLS-DA method performed along with OSC confirmed validation of data analysis. Finally four metabolites are introduced as CD biomarkers.

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Celiac disease (CD) is an immune reaction as a consequence of ingestion of gluten. Diagnosis of CD is not easily using the clinical tests. Then, the discovery of appropriate methods for CD diagnosis is necessary. This study was concentrated to seek the metabolic biomarkers causes of CD compare to healthy subjects.In the present study, we classify CD and healthy subjects using classification and regression tree (CART). To find metabolites in serum which are helpful for the diagnosis of CD, the metabolic profiling was employed using the proton nuclear magnetic resonance spectroscopy ( 1 HNMR). Based on CART results, it was concluded that just using one descriptor, CD and control groups could be classified separately. The 89 % of data in the test set was predicted correctly by the obtained classification model. Our study indicates that quantitative metabolite analysis of serum can be employed to distinguish healthy from CD subjects.