Metabolomics: Basic Principles and Strategies

Metabolomics is the study of metabolome within cells, biofluids, tissues, or organisms to comprehensively identify and quantify all endogenous and exogenous low-molecular-weight (<1 kDa) small molecules/metabolites in a biological system in a high-throughput manner. Metabolomics has several applications in health and disease including precision/personalized medicine, single cell, epidemiologic population studies, metabolic phenotyping, and metabolome-wide association studies (MWAS), precision metabolomics, and in combination with other omics disciplines as integrative omics, biotechnology, and bioengineering. Mass spectrometry (MS)-based metabolomics/lipidomics provides a useful approach for both identification of disease-related metabolites in biofluids or tissue and also encompasses classification and/or characterization of disease or treatment-associated molecular patterns generated from metabolites. Here, in this review, we provide a brief overview of the current status of promising MS-based metabolomics strategies and their emerging roles, as well as possible challenges

A Molecular Case Report of Autosomal Dominant Retinitis Pigmentosa: RP1/RHO Sequence Variants in a Turkish Family

WOS: 000300453800003PubMed ID: 22321012Retinitis pigmentosa (RP) is an inherited progressive retinal disease with a complex inheritance pattern affecting about 1 in 3,500 people worldwide. To date, a large number of sequence changes in the causal contributor genes of wide-spectrum heterogeneous RP were reported, including deletions, insertions, or substitutions that lead missense mutations or truncations. Here we present an association between the clinical presentations of adRP and sequence variants involving novel M216L mutation in the RHO gene together with nonsynonimous sequence changes R872H, N985Y, A1670T, S1691P, C2033Y, and synonimous Q1725Q with novel, N1521N, and T1733T SNPs in the RP1 gene of uncertain pathogenicity in a Turkish family with autosomal dominant retinitis pigmentosa

Pathway-Centric Analysis of the TCGA - NSCLC Transcriptome Data Pertaining to Deceased Patients

Lung cancer among other cancer types is the most prevalent disease with about 1.9 million new cases observed each year and ranks the fifth most common cause of death according to the World Health Organization. Of the two main subtypes of lung cancer, non-small cell lung carcinoma (NSCLC) accounts for the majority of all cases. The two major subtypes of NSCLC, lung squamous cell carcinoma and lung adenocarcinoma are extensively sampled as part of The Cancer Genome Atlas (TCGA) project. In this study, we took a pathway centric focus on the analysis of RNA-Seq data belonging to dead NSCLC patients involved in TCGA. We applied statistical tests comparing subgroups of patients based on varying clinical traits such as tumor pathologic staging and the total number of days passed from diagnosis till death for the subjected patients. We also compared the transcriptome of smokers and nonsmokers to gain insights about the effect of tobacco smoking history on the gene expression patterns of deceased NSCLC patients. Neuroactive ligand-receptor interaction pathway was overrepresented in patients who died at pathologic T2 stage as well as in those lung cancer patients who survived less than a year. Down-regulation of the signaling pathways such as retrograde endocannabinoid, Hippo, AGE-RAGE in diabetic complications, Wnt, and oxytocin was also striking in patients who survived shorter. We show concordant results with previous findings about the down-regulation of nitric oxide synthase in smokers. This study may encourage more focused analyses of the TCGA data with a potential to cast new perspectives onto lung cancer research

Association between RAS Gene Polymorphisms (ACE I/D, AGT M235T) and Henoch-Schönlein Purpura in a Turkish Population

Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity, and renin-angiotensin system (RAS) regulates vascular homeostasis and inflammation with activation of cytokine release. Thus, we aimed to investigate the association between HSP and ACE I/D and AGT M235T polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We obtained a significant difference in genotype distribution (p = 0.003) and allele frequencies (p < 0.001) of ACE I/D polymorphism between patients and controls, while no significant association was detected in genotype distribution (p > 0.05) and allele frequencies (p > 0.05) of the AGT M235T polymorphism. Risk assessment showed significant risk for HSP in the subjects both with the ID + DD genotype (p = 0.019, OR: 2.288, 95% CI: 1.136–4.609) and D allele (OR: D vs. I: 2.0528, 95% CI: 1.3632–3.0912, p = 0.001) while no significant risk was obtained for HSP in the subjects both with the MT + TT genotype (p = 0.312, OR: 1.3905, 95% CI: 0.7326–2.6391) and T allele (OR: T vs. M: 1.065, 95% CI: 0.729–1.557, p = 0.743). Furthermore, when patients were stratified by the presence of certain systemic complications of HSP, no significant association was detected with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D polymorphism is significantly associated with HSP susceptibility

FAS/FASL gene polymorphisms in Turkish patients with chronic myeloproliferative disorders

Introduction : Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. Material and methods : We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Results : Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group (p G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis (p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups (p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations (p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. Conclusions : According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data