The Singapore Lipidomics Incubator: A Model for Engagement and Translation Anne Bendt (Presenter) National University of Singapore Presenter Bio: MSc (Biol), U Greifswald/ Germany PhD (Biochem), U Cologne/ Germany PostDoc (mycobacterial lipidomics), U Singapore Scientific Program Manager; since 2008 Associate Director of the Singapore Lipidomics Incubator; since 2015 Principal Investigator at the Life Sciences Institute/Singapore; since 2015 I am a Principal Investigator in the Singapore Lipidomics Incubator (SLING), anchored within the Life Sciences Institute of the National University of Singapore. In addition to my active research & translation role, I have also been serving as SLING’s Associate Director since 2015. My main research interests include Lipidomics tools and their applications, especially for development of biomarkers and diagnostics; Infectious Diseases; Translation & Commercialization; Operations. More info: https://www.lsi.nus.edu.sg/corp/research-programmes/sling/principal-investigators/anne-k-bendt/

Authors: Anne K Bendt (1), Tze Ping Loh (2) and Markus R Wenk (1,3)
(1) Singapore Lipidomics Incubator (SLING) at the Life Sciences Institute, National University of Singapore; (2) Department of Laboratory Medicine, National University Hospital, Singapore; (3) Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore

We developed a model of engagement to clinically translate LC-MS/MS-based analytical protocols to measure metabolites (lipids, small molecules) in human plasma. By close interactions with data scientists, clinicians and laboratory medicine, we are translating some of our lab-based technology into assays suitable for clinical applications. A special focus lies in understanding natural variation and population reference values. Data from ongoing studies in multi-ethnic cohorts will be discussed.

Introduction

At the Singapore Lipidomics Incubator (SLING), anchored at the National University of Singapore, we have established a program for mass spectrometry-based R&D of lipids (i.e. glycerolipids, sterol lipids, glycerophospholipids, sphingolipids and lyso lipids). Capitalizing primarily on LC-MS/MS we develop robust assays to quantitate lipids and other small molecules from biological specimen such as human plasma. Our initial aim was to advance technologies for lipid research. Now, spurred by increasing interest from clinicians, we are translating some of our methods into assays suitable for clinical adoption, in close interaction with the Department of Laboratory Medicine at the National University Hospital.

Methods

We established a strong team comprising of four core competencies: top-notch lipidomics R&D, data integration, clinical trial capabilities and last but not least laboratory medicine as the envisaged end user. We capitalize on state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) using an Agilent 1290 LC system coupled to a 6490 or a 6495 QQQ. Sample preparation is supported by a liquid handling robotic system (BRAVO). We validate our methods by using an appropriately high number (20-30% of total samples) of quality control samples (technical TQC and batch BQC) and standard reference materials, to ensure reproducibility, accuracy and precision of the lipid quantitation workflow (1).

Results

Besides the development of standardized analytical protocols (1), we have an interest in natural variation and reference values, with a special focus on ethnicity. By having access to plasma from various extensive cohort studies of the multi-ethnic Singapore population (Chinese, Indian and Malay) in comparison with Caucasian cohorts, we begin to understand the natural variation of hundreds of lipid species in human plasma, paving the way towards defining population reference values (2, 3), elucidating disease mechanisms and biomarker discovery. In a number of ongoing clinical studies we are aiming to determine clinical utility of select markers. Our workflow pipelines resulted in hundreds of successful collaborations and accompanying publications, from which some data will be presented.

Conclusions & Discussion

At SLING, we created a model for engagement of key stakeholders to drive the translation of R&D into assays for clinical use and value capture. The close interaction with clinicians indeed was crucial to move from a mere technical ‘push’ towards a clinician’s ‘pull’, i.e. identifying current gaps in the clinical pathway and developing appropriate methods to address unmet diagnostic needs, with a clear application in mind.

1) Burla B et al., Mass spectrometry-based lipidomics of human blood plasma – a community-initiated position paper aimed at developing generally accepted guidelines. J Lipid Res. 2018 Aug 16. doi: 10.1194/jlr.S087163

2) Saw WY et al., ‘Establishing multiple omics baselines for three Southeast Asian populations in the Singapore Integrative Omics Study’. Nat Commun. 2017 Sep 21;8(1):653

3) Begum H et al., ‘Lipidomic profiling of plasma in a healthy Singaporean population to identify ethnic specific differences in lipid levels and associations with disease risk factors’. Clin Mass Spec 6 (2017) 25-31.

We gratefully acknowledge contributions from key personnel from the Singapore Lipidomics Incubator (SLING) at the Life Sciences Institute (LS).The Singapore Lipidomics Incubator receives funding from the Singapore National Research Foundation (NRFI2015-05) and the Life Sciences Institute under the Office of Deputy President for Research and Technology, National University of Singapore.