Checking out the boundaries: Milestone in lipidomics achieved

Results of the first phase of a Ceramide Ring Trial have just been published in the renowned journal Nature Communications, representing a significant landmark in the field of lipidomics. This achievement, involving researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) and scientific teams from all over the world, represents a groundbreaking advance in the establishment of reference values for ceramides, plasma lipids involved in cardiovascular disease risk prediction. The ring trial was initiated and coordinated by SLING, the Singapore Lipidomics Incubator, and performed under the umbrella of the International Lipidomics Society (ILS).

Lipidomics – the large-scale study of pathways and networks of cellular lipids in biological systems – aims to understand the roles of lipids in health and disease by analysing their structures, functions, and interactions in cells. Understanding the upper and lower concentration boundaries of lipids is essential for scientific progress and the clinical translation of lipidomics. To do this, the Ceramide Ring Trial was the first step in assessing technical reproducibility across a global network of laboratories.

It all started with a meeting in Singapore

In a ring trial, multiple laboratories independently analyse the same samples using similar or different methods to compare their results. It helps in assessing the reliability and consistency of measurements across different labs, improving standardisation and quality control in scientific testing.

“It all started with a meeting at NUS between scientists from the major laboratories in the field that agreed that the comparability between lipidomic studies is a major issue,” says Professor Markus Wenk, Dean, College of Health and Life Sciences at Hamad Bin Khalifa University and Visiting Toh Chin Chye Professor in the Department of Biochemistry at NUS Medicine, who initiated this project and is the senior corresponding author on the published study. After seven years of collaborative efforts, the results from 34 participating laboratories across 19 countries have been summarized in a study published in Nature Communications. To reduce complexity, the Ceramide Ring Trial focused on human plasma and aimed to investigate concentration levels and their variabilities of four distinct endogenous ceramides. These lipids play a role in multiple pathologies and have been associated as biomarkers in cardiovascular diseases. Participants of the trial utilized their own preferred analytical method and/or a standardized protocol to quantify ceramides in a human plasma reference material (NIST SRM1950 (used as standard for metabolites in human plasma, provided by the National Institutes of Standards and Technology, NIST) and three additional human plasma reference materials as examples of human diseases such as diabetes, by using specially formulated mixtures of ceramide synthetic standards (from Avanti Polar Lipids) for absolute quantitation.

“This was a true community effort, where most of the labs in the lipidomics field, a private company and the National Institute of Standards and Technology in the United States joined forces with a clear goal in mind. We obtained relevant results for the research community and we benefitted from the expertise of all the groups involved, " explains Assistant Professor Federico Torta from the Department of Biochemistry and the Precision Medicine Translational Research Programme at NUS Medicine and Cardiovascular & Metabolic Disorders research programme at Duke-NUS Medical School.

“The results obtained from different laboratories using different methods and instrumentations were well comparable, better than we initially anticipated,” adds Bo Burla, a senior researcher from the Life Sciences Institute at NUS. “Using specific synthetic standard for absolute quantitation was key to reduce variability and improve accuracy, allowing us to reach consensus in the concentrations of the analytes of interest. This study is the largest and most targeted public inter-laboratory and cross-platform ring trial for distinct ceramides in human plasma and sets a new benchmark for future harmonisation of lipidomics research and beyond”.

For more information, please visit the International Lipidomics Society website: https://lipidomicssociety.org.

Publication in Nature Communications: Federico Torta, Nils Hoffmann, Bo Burla, Irina Alecu, Makoto Arita, Takeshi Bamba, Steffany A. L. Bennett, Justine Bertrand-Michel, Britta Brügger, Mónica P. Cala, Dolores Camacho-Muñoz, Antonio Checa, Michael Chen, Michaela Chocholoušková, Michelle Cinel, Emeline Chu-Van, Benoit Colsch, Cristina Coman, Lisa Connell, Bebiana DaCosta Sousa, Alex M. Dickens, Maria Fedorova, Finnur Freyr Eiríksson, Hector Gallart-Ayala, Mohan Ghorasaini, Martin Giera, Xue Li Guan, Mark Haid, Thomas Hankemeier, Amy Harms, Marcus Höring, Michal Holčapek, Thorsten Hornemann, Chunxiu Hu, Andreas J. Hülsmeier, Kevin Huynh, Christina M. Jones, Julijana Ivanisevic, Yoshihiro Izumi, Harald C. Köfeler, Sin Man Lam, Mike Lange, Jong Cheol Lee, Gerhard Liebisch, Katrice Lippa, Andrea F. Lopez-Clavijo, Malena Manzi, Manuela R. Martinefski, Raviswamy G. H. Math, Satyajit Mayor, Peter J. Meikle, María Eugenia Monge, Myeong Hee Moon, Sneha Muralidharan, Anna Nicolaou, Thao Nguyen-Tran, Valerie B. O’Donnell, Matej Orešič, Arvind Ramanathan, Fabien Riols, Daisuke Saigusa, Tracey B. Schock, Heidi Schwartz-Zimmermann, Guanghou Shui, Madhulika Singh, Masatomo Takahashi, Margrét Thorsteinsdóttir, Noriyuki Tomiyasu, Anthony Tournadre, Hiroshi Tsugawa, Victoria Tyrrell, Grace van der Gugten, Michael O. Wakelam, Craig E. Wheelock, Denise Wolrab, Guowang Xu, Tianrun Xu, John A. Bowden, Kim Ekroos, Robert Ahrends & Markus R. Wenk. Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards

https://www.nature.com/articles/s41467-024-52087-x

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Sally Toh

Head, Communications

Yong Loo Lin School of Medicine

National University of Singapore

Email: sally.toh@nus.edu.sg