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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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Reinders, K.J. (author), Giardina, Giorgia (author), Zurfluh, Florian (author), Ryser, Jurg (author), Hanssen, R.F. (author)In the planning stage of new infrastructure or when designing renovation of existing infrastructure, information about existing slope movements or settlements is essential to make informed design decisions. Interferometric<br/>Synthetic Aperture Radar (InSAR) techniques can be of value to identify these risks in an early stage of a project....journal article 2022
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van Bree, Elisabeth J. (author), Guimarães, Rita L.F.P. (author), Lundberg, Mischa (author), Blujdea, Elena R. (author), Rosenkrantz, Jimi L. (author), White, Fred T.G. (author), Reinders, M.J.T. (author), Holstege, H. (author), Jacobs, Frank M.J. (author)Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci but are not designed to capture all structural variations in the human genome. Using long-read sequencing data, we discovered widespread structural variation within SINE-VNTR-Alu (SVA) elements, a class of great ape-specific transposable...journal article 2022
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Maurits, Marc P. (author), Korsunsky, Ilya (author), Raychaudhuri, Soumya (author), Murphy, Shawn N. (author), Smoller, Jordan W. (author), Weiss, Scott T. (author), Huizinga, Thomas W.J. (author), Reinders, M.J.T. (author), van den Akker, E.B. (author)Objective: To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects. Material and Methods: We used 1872 billing codes in EHRs of 102 880 patients from 12...journal article 2022
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van der Lee, S.J. (author), De Rojas, I. (author), Holstege, H. (author), Hulsman, M. (author), Reinders, M.J.T. (author), Tesi, N. (author), van Rooij, Jeroen (author), Zhao, Y. (author), Zhang, X. (author)Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage<br/>genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found...journal article 2022
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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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Cordes, Martijn (author), Canté-Barrett, Kirsten (author), van den Akker, E.B. (author), Moretti, Federico A. (author), Kiełbasa, Szymon M. (author), Vloemans, Sandra A. (author), Garcia-Perez, Laura (author), Teodosio, Cristina (author), van Dongen, Jacques J.M. (author), Pike-Overzet, K. (author), Reinders, M.J.T. (author), Staal, F.J.T. (author)T cell development in the mouse thymus has been studied extensively, but less is known regarding T cell development in the human thymus. We used a combination of single-cell techniques and functional assays to perform deep immune profiling of human T cell development, focusing on the initial stages of prelineage commitment. We identified...journal article 2022
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Holstege, H. (author), Hulsman, M.J. (author), Charbonnier, Camille (author), Grenier-Boley, Banjamin (author), Quenez, Olivier (author), Grozeva, Detelina (author), van Rooij, Jeroen G.J. (author), Reinders, M.J.T. (author), van der Lee, S.J. (author)Alzheimer’s disease (AD), the leading cause of dementia, has an estimated<br/>heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome...journal article 2022
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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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Mokveld, T.O. (author), Al-Ars, Z. (author), Sistermans, Erik A. (author), Reinders, M.J.T. (author)In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, and often used to infer fetal fractions. We argue that the...journal article 2022
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Bourgonje, Arno R. (author), Hu, Shixian (author), Spekhorst, Lieke M. (author), Zhernakova, Daria V. (author), Vila, Arnau Vich (author), Li, Yanni (author), Charrout, M. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Background and Aims: Protein profiling in patients with inflammatory bowel diseases [IBD] for diagnostic and therapeutic purposes is underexplored. This study analysed the association between phenotype, genotype, and the plasma proteome in IBD. Methods: A total of 92 inflammation-related proteins were quantified in plasma of 1028 patients...journal article 2022
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Dekker, J.J. (author), van Dongen, Jacques J.M. (author), Reinders, M.J.T. (author), Khatri, Indu (author)The IMGT database profiles the TR germline alleles for all four TR loci (TRA, TRB, TRG and TRD), however, it does not comprise of the information regarding population specificity and allelic frequencies of these germline alleles. The specificity of allelic variants to different human populations can, however, be a rich source of information...journal article 2022
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Smit, J.M. (author), Krijthe, J.H. (author), Gommers, D.A.M.P.J. (author), Kamps, M. J.A. (author), Cornet, A.J. (author), Arbous, M. S. (author), De Bruin, D. P. (author), Van Bommel, J. (author), Reinders, M.J.T. (author)Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients...journal article 2022
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Zhang, M. (author), Ganz, Andrea B. (author), Rohde, Susan (author), Rozemuller, Annemieke J.M. (author), Bank, Netherlands Brain (author), Reinders, M.J.T. (author), Scheltens, Philip (author), Hulsman, M. (author), Hoozemans, Jeroen J.M. (author), Holstege, H. (author)Introduction: With increasing age, neuropathological substrates associated with Alzheimer's disease (AD) accumulate in brains of cognitively healthy individuals—are they resilient, or resistant to AD-associated neuropathologies?. Methods: In 85 centenarian brains, we correlated NIA (amyloid) stages, Braak (neurofibrillary tangle) stages, and...journal article 2022
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Ferraro, F. (author), Fevga, Christina (author), Bonifati, Vincenzo (author), Mandemakers, Wim (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Several studies have analyzed gene expression profiles in the substantia nigra to better understand the pathological mechanisms causing Parkinson’s disease (PD). However, the concordance between the identified gene signatures in these individual studies was generally low. This might have been caused by a change in cell type composition as loss...journal article 2022
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Smit, J.M. (author), Krijthe, J.H. (author), Tintu, Andrei N. (author), Endeman, Henrik (author), Ludikhuize, Jeroen (author), van Genderen, Michel E. (author), Gommers, D.A.M.P.J. (author), Arbous, M.S. (author), Reinders, M.J.T. (author)Background: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model...journal article 2022
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Mulder, S.T. (author), Omidvari, Amir-Houshang (author), Rueten-Budde, A.J. (author), Hai, R. (author), Akgün, O.C. (author), Tax, D.M.J. (author), Reinders, M.J.T. (author), Reinders, Marcel (author), Visch, V.T. (author)A digital twin (DT), originally defined as a virtual representation of a physical asset, system, or process, is a new concept in health care. A DT in health care is not a single technology but a domain-adapted multimodal modeling approach incorporating the acquisition, management, analysis, prediction, and interpretation of data, aiming to...journal article 2022
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Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, M. (author), Slagboom, P. E. (author), van den Akker, E.B. (author)Motivation: 1H-NMR metabolomics is rapidly becoming a standard resource in large epidemiological studies to acquire metabolic profiles in large numbers of samples in a relatively low-priced and standardized manner. Concomitantly, metabolomics-based models are increasingly developed that capture disease risk or clinical risk factors. These...journal article 2022
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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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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