Bioinformatics and Virtual Metabolomics Core infrastructure to support omics research in Qatar
Authors: Halama Anna , Zaghlool Shaza , Bhagwat Aditya , Kulinski Michal , Latiff Aishah , Suhre Karsten 
Published: June 2019

Metabolic profiling assembles the information on the small molecule (metabolites) composition in the body. There are several factors like genetic makeup, protein abundance, environment, life habits or gut microbiota, which all contribute to “metabolic fingerprint” - specific for each individual. Metabolomics can be deployed to draw a map of metabolic interactions associated with diseased condition; characteristic metabolic alterations can be used to monitor disease onset, progression or response to the treatment. For instance, alteration in branch chain amino acids, aromatic amino acids and lipids was associated with prediction of type 2 diabetes (T2D). Furthermore, elevated level of 1,5-anhydroglucitol (1,5-AG) in plasma and saliva samples was determined by us and by others as biomarker, complementary to Hba1C, for detection and monitoring of T2D. Metabolomics study requires expertise in experimental design, sample measurements and data analysis to produce meaningful, reliable and reproducible data. Metabolomics data can be further integrated with other “omics” including transcriptomics, proteomics, glycomics and methylomics. Here we are presenting the “Bioinformatics and Virtual Metabolomics Core”, an infrastructure, which we established in Qatar to enable metabolic profiling as well as analysis of highly complex “omics” data. To perform metabolomics study the following components are required: 1) Technology providing reliable data with high quality; 2) Pipeline for data processing; 3) Expertise in data interpretation. 1) We were actively involved in establishment of targeted and non-targeted metabolomics platforms in Qatar. Targeted platform: In collaboration with Translational Research Institute (TRI) we established targeted metabolomics platform able to quantify 163 metabolites including amino acids, carnitines, phosphatidylcholines, lysophospholipids and sphingomyelins. This platform is deploying Absolute IDQ Biocrates Kit technology for sample preparation and processing. The measurements are performed using flow injection analysis (FIA) - mass spectrometry (MS) technology based on combined ExigentEksperLC100 and QTRAP4500 (ABSCIEX). Evaluation of the mass spectrometry data is performed with MetIDQ software package (integral part of the Absolute IDQ assay). Untargeted platform: We were involved in the process of untargeted platform establishment. This platform is hosted and operated by Anti-Doping Lab Qatar (ADLQ) and enables for semi quantitative profiling of metabolites in human biofluids, tissue samples and cell culture. The protocols for sample processing and preparation were optimized by Metabolon and are conducted in Qatar accordingly. These measurements are deploying Waters ACQUITY ultra-performance liquid chromatography (UPLC) and a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer. Compounds identification is performed by comparison of peaks to library entries of purified standards based on retention index (RI). 2) The metabolomics study generates large amount of highly complex data, which requires further data processing. We have developed an internal pipeline for data processing, including quality control and data normalization. For visualization purposes we use Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures (OPLS). Statistical data analysis is tailored according to the experimental design and data structure. We are using web-tools to enable our customer direct data access. We also developed a tool called “AUTONOMICS” for automated data analysis, which can serve more advanced users. 3) Our team is extensively working with metabolomics data; we are using Gaussian graphical modeling to reconstruct metabolic pathways and to draw network of interactions between metabolites. For pathway analysis and data interpretation we are using KEGG database, Ingenuity® Pathway Analysis (IPA®) and our experience. To provide detailed overview on human disease including diabetes, kidney and liver disorders as well as cancer we are combining metabolomics with other “omics” data. Our expertise lies in processing and evaluation of data from human biofluids (urine, plasma, saliva). The team is also specialized in metabolomics in cell culture; we developed a pipeline for cell culture-optimized sample collection and processing. In conclusion, our platform was established to enable fully comprehensive metabolomics study in Qatar, which will serve local scientific community. We are supporting our collaborators and users over the whole process related to metabolomics study including experimental design, sample processing, metabolite measurements and data analysis.