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The AccelerAge framework: a new statistical approach to predict biological age based on time-to-event data

Sluiskes, Marije (author), Goeman, Jelle (author), Beekman, Marian (author), Slagboom, Eline (author), van den Akker, E.B. (author), Putter, H. (author), Rodríguez-Girondo, Mar (author)

Aging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While chronological age serves as a strong risk factor for age-related health conditions, considerable heterogeneity exists in the aging trajectories of...

journal article 2024

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Upstream process development for cultured red blood cell production

Gallego Murillo, Joan Sebastián (author)

Production of cultured red blood cells (cRBCs) hold the promise of being a potentially unlimited source of cells that could cover the increasing demand of RBCs for transfusion purposes, while having more control on the quality and safety of the cells compared to the current donor-dependent system. cRBCs could also be used for novel therapies in...

doctoral thesis 2023

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Explainable AI for metabolic engineering

van Graft, Tijmen (author)

Metabolic engineering is an important field in biotechnology, aimed at optimizing cellular processes to produce desired compounds. In this thesis, we focus on predicting the metabolome from the proteome, as understanding this relationship is crucial for understanding cellular metabolism. We investigate the usage of additional biological...

master thesis 2023

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Technical Report: A Comprehensive Comparison between Different Quantification Versions of Nightingale Health’s 1H-NMR Metabolomics Platform

Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, Marian (author), Slagboom, P. Eline (author), van den Akker, E.B. (author)

1H-NMR metabolomics data is increasingly used to track health and disease. Nightingale Health, a major supplier of 1H-NMR metabolomics, has recently updated the quantification strategy to further align with clinical standards. Such updates, however, might influence backward replicability, particularly affecting studies with repeated measures....

journal article 2023

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Benchmarking Outlier Detection Methods for Detecting IEM Patients in Untargeted Metabolomics Data

Bongaerts, Michiel (author), Kulkarni, Purva (author), Zammit, Alan (author), Bonte, Ramon (author), Kluijtmans, Leo A. J. (author), Blom, Henk J. (author), Engelke, Udo F. H. (author), Tax, D.M.J. (author), Ruijter, George J.G. (author), Reinders, M.J.T. (author)

Untargeted metabolomics (UM) is increasingly being deployed as a strategy for screening patients that are suspected of having an inborn error of metabolism (IEM). In this study, we examined the potential of existing outlier detection methods to detect IEM patient profiles. We benchmarked 30 different outlier detection methods when applied to...

journal article 2023

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Integration of metabolomics with genomics: Metabolic gene prioritization using metabolomics data and genomic variant (CADD) scores

Bongaerts, Michiel (author), Bonte, Ramon (author), Demirdas, Serwet (author), Huidekoper, Hidde H. (author), Langendonk, Janneke (author), Wilke, Martina (author), de Valk, Walter (author), Blom, Henk J. (author), Reinders, M.J.T. (author), Ruijter, George J.G. (author)

The integration of metabolomics data with sequencing data is a key step towards improving the diagnostic process for finding the disease-causing genetic variant(s) in patients suspected of having an inborn error of metabolism (IEM). The measured metabolite levels could provide additional phenotypical evidence to elucidate the degree of...

journal article 2022

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Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation

Wang, Gangqi (author), Heijs, Bram (author), Kostidis, Sarantos (author), Rietjens, Rosalie G.J. (author), Mahfouz, A.M.E.T.A. (author), Chuva de Sousa Lopes, Susana M. (author), van den Berg, Cathelijne W. (author), van den Berg, Bernard M. (author), Rabelink, Ton J. (author)

Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess metabolism at a spatial resolution that acknowledges both heterogeneity and cellular dynamics in its tissue microenvironment. Using a multi-omics platform to study cell-type-specific dynamics in metabolism in...

journal article 2022

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GlycA, a Biomarker of Low-Grade Inflammation, Is Increased in Male Night Shift Workers

Bizzarri, D. (author), Dollé, Martijn E. T. (author), Loef, Bette (author), van den Akker, E.B. (author), van Kerkhof, Linda W. M. (author)

Sustained night shift work is associated with various adverse health risks, including an increased risk of cardiovascular disease, type II diabetes, and susceptibility to infectious respiratory diseases. The extent of these adverse health effects, however, seems to greatly vary between night shift workers, yet the underlying reasons and the...

journal article 2022

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Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli

Minden, Steven (author), Aniolek, Maria (author), Sarkizi Shams Hajian, Christopher (author), Teleki, Attila (author), Zerrer, Tobias (author), Delvigne, Frank (author), van Gulik, W.M. (author), Deshmukh, Amit (author), Noorman, H.J. (author), Takors, Ralf (author)

Carbon limitation is a common feeding strategy in bioprocesses to enable an efficient microbiological conversion of a substrate to a product. However, industrial settings inherently promote mixing insufficiencies, creating zones of famine conditions. Cells frequently traveling through such regions repeatedly experience substrate shortages and...

journal article 2022

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Metabolomic predictors of phenotypic traits can replace and complement measured clinical variables in population-scale expression profiling studies

Niehues, Anna (author), Bizzarri, Daniele (author), Reinders, M.J.T. (author), Slagboom, P. Eline (author), van Gool, Alain J. (author), van den Akker, E.B. (author), 't Hoen, Peter A.C. (author)

Population-scale expression profiling studies can provide valuable insights into biological and disease-underlying mechanisms. The availability of phenotypic traits is essential for studying clinical effects. Therefore, missing, incomplete, or inaccurate phenotypic information can make analyses challenging and prevent RNA-seq or other omics...

journal article 2022

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PLIS: A metabolomic response monitor to a lifestyle intervention study in older adults

Bogaards, Fatih A. (author), Gehrmann, Thies (author), Beekman, Marian (author), van den Akker, E.B. (author), van de Rest, Ondine (author), Hangelbroek, Roland W.J. (author), Noordam, Raymond (author), Mooijaart, Simon P. (author), Reinders, M.J.T. (author)

The response to lifestyle intervention studies is often heterogeneous, especially in older adults. Subtle responses that may represent a health gain for individuals are not always detected by classical health variables, stressing the need for novel biomarkers that detect intermediate changes in metabolic, inflammatory, and immunity-related...

journal article 2022

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Fast sampling of the cellular Metabolome

van Gulik, W.M. (author), Canelas, A (author), Nikerel, I.E. (author), Douma, RD (author), de Jonge, L.P. (author), Heijnen, J.J. (author)

Obtaining meaningful snapshots of the metabolome of microorganisms requires rapid sampling and immediate quenching of all metabolic activity, to prevent any changes in metabolite levels after sampling. Furthermore, a suitable extraction method is required ensuring complete extraction of metabolites from the cells and inactivation of enzymatic...

book chapter 2022

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1H-NMR metabolomics-based surrogates to impute common clinical risk factors and endpoints

Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, M. (author), Slagboom, P. E. (author), van den Akker, E.B. (author)

Background: Missing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples, i.e. ‘metabolomics’, is steadily gaining popularity, as it is highly informative for various phenotypical characteristics. Here we aim to leverage...

journal article 2022

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Protocol for multimodal analysis of human kidney tissue by imaging mass spectrometry and CODEX multiplexed immunofluorescence

Neumann, Elizabeth K. (author), Patterson, Nathan Heath (author), Allen, Jamie L. (author), Migas, L.G. (author), Yang, Haichun (author), Brewer, Maya (author), Anderson, David M. (author), Harvey, Jennifer (author), Harris, Raymond C. (author), Van de Plas, Raf (author)

Here, we describe the preservation and preparation of human kidney tissue for interrogation by histopathology, imaging mass spectrometry, and multiplexed immunofluorescence. Custom image registration and integration techniques are used to create cellular and molecular atlases of this organ system. Through careful optimization, we ensure high...

journal article 2021

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Prospects for multi-omics in the microbial ecology of water engineering

McDaniel, Elizabeth A. (author), Wahl, S.A. (author), Ishii, Shun'ichi (author), Pinto, Ameet (author), Ziels, Ryan (author), Nielsen, Per Halkjær (author), McMahon, Katherine D. (author), Williams, Rohan B.H. (author)

Advances in high-throughput sequencing technologies and bioinformatics approaches over almost the last three decades have substantially increased our ability to explore microorganisms and their functions – including those that have yet to be cultivated in pure isolation. Genome-resolved metagenomic approaches have enabled linking powerful...

review 2021

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Investigating the chemolithoautotrophic and formate metabolism of nitrospira moscoviensis by constraint-based metabolic modeling and ¹³C-tracer analysis

Lawson, Christopher E. (author), Mundinger, Aniela B. (author), Koch, Hanna (author), Jacobson, Tyler B. (author), Weathersby, Coty A. (author), Jetten, Mike S.M. (author), Pabst, Martin (author), Amador-Noguez, Daniel (author), Noguera, Daniel R. (author)

Nitrite-oxidizing bacteria belonging to the genus Nitrospira mediate a key step in nitrification and play important roles in the biogeochemical nitrogen cycle and wastewater treatment. While these organisms have recently been shown to exhibit metabolic flexibility beyond their chemolithoautotrophic lifestyle, including the use of simple...

journal article 2021

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Lifestyle-Intervention-Induced Reduction of Abdominal Fat Is Reflected by a Decreased Circulating Glycerol Level and an Increased HDL Diameter

Beekman, Marian (author), Schutte, Bianca A.M. (author), van den Akker, E.B. (author), Noordam, Raymond (author), Dibbets-Schneider, Petra (author), de Geus-Oei, Lioe Fee (author), Deelen, Joris (author), Rest, Ondine van de (author), Heemst, Diana van (author)

Scope: Abdominal obesity is one of the main modifiable risk factors of age-related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, cholesterol, and glucose concentrations can be reduced by a healthier lifestyle. Hence, the aim is to understand the relation between lifestyle-induced changes in...

journal article 2020

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Using out-of-batch reference populations to improve untargeted metabolomics for screening inborn errors of metabolism

Bongaerts, Michiel (author), Bonte, Ramon (author), Demirdas, Serwet (author), Jacobs, Edwin H. (author), Oussoren, Esmee (author), van der Ploeg, Ans T. (author), Wagenmakers, Margreet A.E.M. (author), Hofstra, Robert M.W. (author), Blom, Henk J. (author), Reinders, M.J.T. (author), Ruijter, George J.G. (author)

Untargeted metabolomics is an emerging technology in the laboratory diagnosis of inborn errors of metabolism (IEM). Analysis of a large number of reference samples is crucial for correcting variations in metabolite concentrations that result from factors, such as diet, age, and gender in order to judge whether metabolite levels are abnormal....

journal article 2020

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Proximate mechanisms of drought resistance in Phytoseiulus persimilis eggs

Le Hesran, Sophie (author), Groot, Thomas (author), Knapp, Markus (author), Nugroho, Jovano Erris (author), Beretta, Giuditta (author), Salomé-Abarca, Luis Francisco (author), Choi, Young Hae (author), Vancová, Marie (author), Moreno Rodenas, A. (author), Dicke, Marcel (author)

Under drought stress, Phytoseiulus persimilis females are able to lay drought-resistant eggs through an adaptive maternal effect. The mechanisms making these eggs drought resistant still remain to be investigated. For this purpose, we studied the physiological differences between drought-resistant and drought-sensitive eggs. We compared the...

journal article 2019

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Metabolic adjustment upon repetitive substrate perturbations using dynamic ¹³C-tracing in yeast

Suarez Mendez, C.A. (author), Ras, C. (author), Wahl, S.A. (author)

Background: Natural and industrial environments are dynamic with respect to substrate availability and other conditions like temperature and pH. Especially, metabolism is strongly affected by changes in the extracellular space. Here we study the dynamic flux of central carbon metabolism and storage carbohydrate metabolism under dynamic feast...

journal article 2017