Ensuring sample quality for biomarker discovery studies - Use of ict tools to trace biosample life-cycle

The growing demand of personalized medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological material and its accompanying data are collected, handled and stored in accordance with standard operating procedures (SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life-cycle can be recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research facilities and will represent the starting point of all future personalized medicine-based clinical trials

Toward a Standardized Strategy of Clinical Metabolomics for the Advancement of Precision Medicine

Despite the tremendous success, pitfalls have been observed in every step of a clinical metabolomics workflow, which impedes the internal validity of the study. Furthermore, the demand for logistics, instrumentations, and computational resources for metabolic phenotyping studies has far exceeded our expectations. In this conceptual review, we will cover inclusive barriers of a metabolomics-based clinical study and suggest potential solutions in the hope of enhancing study robustness, usability, and transferability. The importance of quality assurance and quality control procedures is discussed, followed by a practical rule containing five phases, including two additional "pre-pre-" and "post-post-" analytical steps. Besides, we will elucidate the potential involvement of machine learning and demonstrate that the need for automated data mining algorithms to improve the quality of future research is undeniable. Consequently, we propose a comprehensive metabolomics framework, along with an appropriate checklist refined from current guidelines and our previously published assessment, in the attempt to accurately translate achievements in metabolomics into clinical and epidemiological research. Furthermore, the integration of multifaceted multi-omics approaches with metabolomics as the pillar member is in urgent need. When combining with other social or nutritional factors, we can gather complete omics profiles for a particular disease. Our discussion reflects the current obstacles and potential solutions toward the progressing trend of utilizing metabolomics in clinical research to create the next-generation healthcare system.11Ysciescopu

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes

The human early-life exposome (HELIX): project rationale and design

Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome

Challenges Associated With the Design and Deployment of Food Intake Urine Biomarker Technology for Assessment of Habitual Diet in Free-Living Individuals and Populations:A Perspective

Improvement of diet at the population level is a cornerstone of national and international strategies for reducing chronic disease burden. A critical challenge in generating robust data on habitual dietary intake is accurate exposure assessment. Self-reporting instruments (e.g., food frequency questionnaires, dietary recall) are subject to reporting bias and serving size perceptions, while weighed dietary assessments are unfeasible in large-scale studies. However, secondary metabolites derived from individual foods/food groups and present in urine provide an opportunity to develop potential biomarkers of food intake (BFIs). Habitual dietary intake assessment in population surveys using biomarkers presents several challenges, including the need to develop affordable biofluid collection methods, acceptable to participants that allow collection of informative samples. Monitoring diet comprehensively using biomarkers requires analytical methods to quantify the structurally diverse mixture of target biomarkers, at a range of concentrations within urine. The present article provides a perspective on the challenges associated with the development of urine biomarker technology for monitoring diet exposure in free-living individuals with a view to its future deployment in real world situations. An observational study (n = 95), as part of a national survey on eating habits, provided an opportunity to explore biomarker measurement in a free-living population. In a second food intervention study (n = 15), individuals consumed a wide range of foods as a series of menus designed specifically to achieve exposure reflecting a diversity of foods commonly consumed in the UK, emulating normal eating patterns. First Morning Void urines were shown to be suitable samples for biomarker measurement. Triple quadrupole mass spectrometry, coupled with liquid chromatography, was used to assess simultaneously the behavior of a panel of 54 potential BFIs. This panel of chemically diverse biomarkers, reporting intake of a wide range of commonly-consumed foods, can be extended successfully as new biomarker leads are discovered. Towards validation, we demonstrate excellent discrimination of eating patterns and quantitative relationships between biomarker concentrations in urine and the intake of several foods. In conclusion, we believe that the integration of information from BFI technology and dietary self-reporting tools will expedite research on the complex interactions between dietary choices and health. (c) Copyright (c) 2020 Beckmann, Wilson, Lloyd, Torres, Goios, Willis, Lyons, Phillips, Mathers and Draper