Leistner, D. M. | Search bioRxiv

bioRxiv2020

Concepts and Software Package for Efficient Quality Control in Targeted Metabolomics Studies - MeTaQuaC

Targeted quantitative mass spectrometry metabolite profiling is the workhorse of metabolomics research. Robust and reproducible data is essential for confidence in analytical results and is particularly important with large-scale studies. Commercial kits are now available which use carefully calibrated and validated internal and external standards to provide such reliability. However, they are still subject to processing and technical errors in their use and should be subject to a laboratorys routine quality assurance and quality control measures to maintain confidence in the results. We discuss important systematic and random measurement errors when using these kits and suggest measures to detect and quantify them. We demonstrate how wider analysis of the entire dataset, alongside standard analyses of quality control samples can be used to identify outliers and quantify systematic trends in order to improve downstream analysis. Finally we present the MeTaQuaC software which implements the above concepts and methods for Biocrates kits and creates a comprehensive quality control report containing rich visualization and informative scores and summary statistics. Preliminary unsupervised multivariate analysis methods are also included to provide rapid insight into study variables and groups. MeTaQuaC is provided as an open source R package under a permissive MIT license and includes detailed user documentation.

bioinformatics↗

bioRxiv2019

Cohort profile: The LipidCardio Study - Role of Lipoproteins in Cardiovascular Disease

PurposeThe LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. Particularly the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease will be a main focus.\n\nParticipants1.005 individuals aged 21 years and older undergoing cardiac catheterization during 17 months at a tertiary academic cardiology center were enrolled. The baseline data set contains detailed phenotyping, broad biochemical parameters, genetic data, but also standardized personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, amongst others. Blood samples were stored in a biobank for future analyses.\n\nFindings to dateThe mean age of the participants at enrolment was 70.9{+/-}11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of cardiovascular disease than participants without CAD.\n\n20% of patients had lipoprotein(a) [Lp(a)] concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared to participants in quintiles 1-4 (OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in the LPA gene (rs10455872, rs3798220 and rs186696265) and the APOE gene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank.\n\nFuture plansMortality information will be obtained in two-year intervals. Follow-up phone interviews will be conducted at 3, and 6 years after enrolment. We seek to cooperate with other researchers in the field, e.g. by sharing data and biobank samples.\n\nRegistrationnot applicable, purely observational study

epidemiology↗