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Role of Tandem Mass Spectrometry in Diagnosis and Management of Inborn Errors of Metabolism
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Kannan Vaidyanathan, Sandhya Gopalakrishnan
Unprocessed oligosaccharides and glycoconjugates were detected in urine in patients with glycoproteinosis, Pompe’s disease and sialic acid storage diseases by MALDI-TOF-MS [81]. Urinary analysis of free oligosaccharides by MALDI/TOF/TOF aids the diagnosis of lysosomal storage disorders [82]. Using label-free quantitative proteomics, two potential markers, prosaposin, and GM2 activator protein (GM2AP), were identified in urine of pediatric patients for pre-symptomatic kidney disease in Type I diabetes and Fabry disease [83]. An LC-MS/MS method for the simultaneous determination of homovanillic acid, VMA, orotic acid and homogentisic acid in urine has been developed [84]. Acylglycines are important metabolites for the diagnosis of a number of IEM. A UPLC/MS method was developed for the assay of acylglycines in urine samples [85]. Urinary steroids were analyzed in patients with 21 hydroxylase deficiency by GC-MS/MS. Many novel steroids some of which may be used as biomarkers were identified [86]. Large number of putative IEM markers was identified in urine by ESI-MS/MS technique by Rebollido-Fernandez et al. [87]. An analytical method for the detection of pterins in urine for the identification of both typical and atypical PKU has been described [88].
Omics and perinatal medicinePreeclampsia
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Piya Chaemsaithong, Liona C. Poon
One study used isobaric tag for relative and absolute quantitation (iTRAQ) analysis of maternal plasma samples taken at 12 weeks of gestation. iTRAQ is a relatively new quantitative proteomics technique applicable to bottom-up mass spectrometry (157–159). Advantages of this technique are that a protein can be identified and quantified from data of multiple peptides often with multiple values per distinct peptide, thereby enhancing confidence in both identity and abundance. In addition, several samples can be combined and analyzed together. The authors found that there were 31 upregulated proteins and 20 downregulated proteins in patients who subsequently developed PE (n = 5), demonstrating the potential for the development of a first trimester screening model for PE using proteomics (160).
Functional Omics and Big Data Analysis in Microalgae
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Chetan Paliwal, Tonmoy Ghosh, Asha A. Nesamma, Pavan P. Jutur
More recently, due to the importance being attached to algal-derived third-generation biofuels, researchers have shifted their focus and tried to study quantitative proteomics in different algal species under stress conditions. A proteome study was reported in Nannochloropsis oculata under nitrogen starvation (Tran et al. 2016), and several heat shock proteins in C. reinhardtii were down-regulated during short duration, high light stress (Mahong et al. 2012). Nitrogen starvation stimulus helps to study the various responses of C. reinhardtii in the transcriptome, proteome, and photosynthetic metabolism (Schmollinger et al. 2014) and similarly in Tisochrysis lutea and Neochloris oleoabundans (Garnier et al. 2014; Morales-Sánchez et al. 2016). Recently, lipid droplet surface protein was identified in selected microalgae strains, and this new identification could develop a better understanding of organelle dynamics (Sirikhachornkit et al. 2018). The response of microalgae to N starvation and the corresponding changes happening in the proteome are very useful for the prediction of metabolic pathways, and knowledge is very crucial if we are to be able to stimulate desired fatty acid or triacylglycerol (TAG) accumulation.
Integrating analysis of proteome profile and drug screening identifies therapeutic potential of MET pathway for the treatment of malignant peripheral nerve sheath tumor
Published in Expert Review of Proteomics, 2023
Ryuto Tsuchiya, Yuki Yoshimatsu, Rei Noguchi, Yooksil Sin, Takuya Ono, Taro Akiyama, Hidetaka Kosako, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo
In an attempt to identify potential therapeutic agents, precision medicine based on genomic information has been actively conducted in recent years [9,10]. However, <10% of patients are eligible for precision medicine, indicating that current genome-based precision medicine has limitations [11]. As a preclinical method of identifying new therapeutic agents, pharmaco-genomics, a screening technique that collects the genomic and pharmacologic profiles of the tumor using various cell lines, has been increasingly highlighted [12–16]. However, in vitro drug responses were not completely consistent with those in patients. The failure of these approaches is partly due to the discrepancy between the genome and protein expression and post-translational modifications of the proteins [17,18]. Thus, it is important to focus on proteomics, in addition to genomics. Proteomic profiles provide information regarding the biological phenotypes more directly than genetic profiles, thereby aiding in the identification of disease pathways, diagnostic biomarkers, and therapeutic targets [19]. In particular, quantitative proteomics is useful in drug discovery because it enables the stratification of samples according to protein expression levels [20].
Differential expression of MAP3K7 and TROPONIN C proteins and related perturbations in renal amyloidosis
Published in Expert Review of Proteomics, 2020
Nimisha Gupta, Tahreem Sahar, Dinesh Khullar, S.K. Jain, Saima Wajid
Serum samples from both diseased and control groups when electrophoresed in two dimensions, revealed significant differences in terms of intensity and number of the spots present in both the gels, followed by PD – Quest analysis. Among differentially expressed spots, eight spots (SSP 1507, SSP 2303, SSP 2408, SSP 3405, SSP 1305, SSP 2204, SSP 7103 and SSP 5104) were further selected for characterization by MALDI-TOF-MS PMF. Out of eight spots, four spots (SSP 2408, SSP 5104, SSP 1305 and SSP 7103) were found to be qualitative while another four spots were found to be quantitative (SSP 1507, SSP 2303, SSP 3405 and SSP 2204) as shown in Figure 1. Quantitative proteomics yields information about the physiological differences between two biological samples. On the other hand, qualitative proteomics is the general method used for protein identification. The qualitative proteins are present either in the control or diseased sample while the quantitative protein spots are present in both the control and diseased sample. Supplementary Figure 2–9 shows master gel, pop-up graphs and spot parameters displaying visual alterations of selected identified spots that validate the SSP calculations.
Proteomic examination of the neuroglial secretome: lessons for the clinic
Published in Expert Review of Proteomics, 2020
Jong-Heon Kim, Ruqayya Afridi, Won-Ha Lee, Kyoungho Suk
Recently, a modified dual Stable Isotope Labeling by/with Amino acids in Cell culture (SILAC) labeling strategy was adopted to analyze the secretome profile of astrocytes isolated from the rat forebrain [50]. Owing to the dual labeling technology used in the study, the group identified more than 2,000 proteins in astrocytic conditioned medium. The study highlights the supremacy of quantitative proteomics over qualitative proteomic techniques. The inflammatory activation of astrocytes, as observed in neurological disorders, impacts neuronal health, leading to neuronal degeneration and dysfunction [51]. Increased levels of IL-1β and GM-CSF were detected using enzyme-linked immunosorbent assay (ELISA) in astrocytic condition medium treated with cytochrome C (CytC) [51]. CytC is secreted by neurotoxic glial cells and can exacerbate ongoing neuroinflammation after release into the extracellular space by activating astrocytes and microglia through autocrine effects [51]. A recent study identified alterations in the astrocytic secretome induced by activation of the unfolded protein response (UPR), leading to neuronal damage. The conditioned medium from UPR-activated astrocytes was analyzed using liquid chromatography–mass spectrometry (LC/MS), and several proteins were found to be differentially expressed in conditioned medium obtained from the activated astrocytes [52]. The differentially expressed proteins were mostly chaperones important for the folding and synthesis of proteins in the endoplasmic reticulum.