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Keo, D.L. (author), Mahfouz, A.M.E.T.A. (author), Ingrassia, Angela M.T. (author), Meneboo, Jean Pascal (author), Villenet, Celine (author), Mutez, Eugénie (author), Comptdaer, Thomas (author), Lelieveldt, B.P.F. (author), Reinders, M.J.T. (author)The molecular mechanisms underlying caudal-to-rostral progression of Lewy body pathology in Parkinson’s disease remain poorly understood. Here, we identified transcriptomic signatures across brain regions involved in Braak Lewy body stages in non-neurological adults from the Allen Human Brain Atlas. Among the genes that are indicative of...journal article 2020
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Scheltens, Philip (author), van der Flier, Wiesje M. (author), Huisman, Martijn (author), Reinders, M.J.T. (author), Holstege, H. (author)Developing Alzheimer’s disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what...journal article 2020
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Groß, C. (author), Bortoluzzi, Chiara (author), de Ridder, Dick (author), Megens, Hendrik-Jan (author), Groenen, Martien A.M. (author), Reinders, M.J.T. (author), Bosse, Mirte (author)The availability of genomes for many species has advanced our understanding of the non-protein-coding fraction of the genome. Comparative genomics has proven itself to be an invaluable approach for the systematic, genome-wide identification of conserved non-protein-coding elements (CNEs). However, for many non-mammalian model species,...journal article 2020
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Makrodimitris, S. (author), van Ham, R.C.H.J. (author), Reinders, M.J.T. (author)The current rate at which new DNA and protein sequences are being generated is too fast to experimentally discover the functions of those sequences, emphasizing the need for accurate Automatic Function Prediction (AFP) methods. AFP has been an active and growing research field for decades and has made considerable progress in that time....review 2020
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Linthorst, J. (author), Meert, Wim (author), Hestand, Matthew S. (author), Korlach, Jonas (author), Vermeesch, Joris Robert (author), Reinders, M.J.T. (author), Holstege, H. (author)The human genome harbors numerous structural variants (SVs) which, due to their repetitive nature, are currently underexplored in short-read whole-genome sequencing approaches. Using single-molecule, real-time (SMRT) long-read sequencing technology in combination with FALCON-Unzip, we generated a de novo assembly of the diploid genome of a...journal article 2020
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Abdelaal, T.R.M. (author), Mourragui, S.M.C. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Single-cell technologies are emerging fast due to their ability to unravel the heterogeneity of biological systems. While scRNA-seq is a powerful tool that measures whole-transcriptome expression of single cells, it lacks their spatial localization. Novel spatial transcriptomics methods do retain cells spatial information but some methods can...journal article 2020
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Hagenbeek, Fiona A. (author), Bomer, N. (author), van Hilten, J. A. (author), Fu, J. (author), van der Heijden, A. A.W.A. (author), van der Spek, A. (author), Boersma, E. (author), van den Akker, E.B. (author), Reinders, M.J.T. (author)Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November...journal article 2019
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Deelen, J (author), D., Evans (author), Dan E., Arking (author), Tesi, N. (author), M, Nygaard (author), Liu, Xiaoming (author), Mary K., Wojczynski (author), Reinders, M.J.T. (author), Holstege, H. (author)Human longevity is heritable, but genome-wide association (GWA) studies have had limitedsuccess. Here, we perform two meta-analyses of GWA studies of a rigorous longevityphenotype definition including 11,262/3484 cases surviving at or beyond the age corre-sponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose...journal article 2019
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Meijers-Heijboer, Hanne (author), Reinders, M.J.T. (author), Holstege, H. (author)The detection of genetic loci associated with Alzheimer’s disease (AD) requires large numbers of cases and controls because variant effect sizes are mostly small. We hypothesized that variant effect sizes should increase when individuals who represent the extreme ends of a disease spectrum are considered, as their genomes are assumed to be...journal article 2019
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Makrodimitris, S. (author), van Ham, R.C.H.J. (author), Reinders, M.J.T. (author)Motivation: Most automatic functional annotation methods assign Gene Ontology (GO) terms to proteins based on annotations of highly similar proteins. We advocate that proteins that are less similar are still informative. Also, despite their simplicity and structure, GO terms seem to be hard for computers to learn, in particular the Biological...journal article 2019
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Abdelaal, T.R.M. (author), van Unen, Vincent (author), Höllt, T. (author), Koning, Frits (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Mass cytometry by time-of-flight (CyTOF) is a valuable technology for high-dimensional analysis at the single cell level. Identification of different cell populations is an important task during the data analysis. Many clustering tools can perform this task, which is essential to identify “new” cell populations in explorative experiments....journal article 2019
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Mourragui, S.M.C. (author), Loog, M. (author), van der Wiel, Mark A. (author), Reinders, M.J.T. (author), Wessels, L.F.A. (author)Motivation: Cell lines and patient-derived xenografts (PDXs) have been used extensively to understand the molecular underpinnings of cancer. While core biological processes are typically conserved, these models also show important differences compared to human tumors, hampering the translation of findings from pre-clinical models to the human...journal article 2019
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Abdelaal, T.R.M. (author), Michielsen, L.C.M. (author), Cats, Davy (author), Hoogduin, Dylan (author), Mei, Hailiang (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Background: Single-cell transcriptomics is rapidly advancing our understanding of the cellular composition of complex tissues and organisms. A major limitation in most analysis pipelines is the reliance on manual annotations to determine cell identities, which are time-consuming and irreproducible. The exponential growth in the number of...journal article 2019
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Abdelaal, T.R.M. (author), Höllt, T. (author), van Unen, Vincent (author), Lelieveldt, B.P.F. (author), Koning, Frits (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Motivation: High-dimensional mass cytometry (CyTOF) allows the simultaneous measurement of multiple cellular markers at single-cell level, providing a comprehensive view of cell compositions.<br/>However, the power of CyTOF to explore the full heterogeneity of a biological sample at the singlecell level is currently limited by the number of...journal article 2019
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van der Lee, S.J. (author), Conway, Olivia J. (author), Hansen, Iris (author), Carrasquillo, Minerva M. (author), Kleineidam, Luca (author), van den Akker, E.B. (author), Hulsman, M. (author), Tesi, N. (author), Reinders, M.J.T. (author)The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer’s disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven...journal article 2019
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Koorneef, Lisa L. (author), Bogaards, Marit (author), Reinders, M.J.T. (author), Meijer, Onno C. (author), Mahfouz, A.M.E.T.A. (author)Metabolic status impacts on the emotional brain to induce behavior that maintains energy balance. While hunger suppresses the fear circuitry to promote explorative food-seeking behavior, satiety or obesity may increase fear to prevent unnecessary risk-taking. Here we aimed to unravel which metabolic factors, that transfer information about...journal article 2018
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Gehrmann, T. (author), Pelkmans, Jordi F. (author), Ohm, Robin A. (author), Vos, A.M. (author), Sonnenberg, Anton S.M. (author), Baars, Johan J.P. (author), Wösten, Han A.B. (author), Reinders, M.J.T. (author), Abeel, T.E.P.M.F. (author)Many fungi are polykaryotic, containing multiple nuclei per cell. In the case of heterokaryons, there are different nuclear types within a single cell. It is unknown what the different nuclear types contribute in terms of mRNA expression levels in fungal heterokaryons. Each cell of the mushroom Agaricus bisporus contains two to 25 nuclei of...journal article 2018
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- Jürgenhake, Birgit (author), Reinders, L.G.A.J. (author) abstract 2018
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Derks, Martijn F.L. (author), Megens, Hendrik-Jan (author), Bosse, Mirte (author), Visscher, Jeroen (author), Peeters, Katrijn (author), Bink, Marco C.A.M. (author), Vereijken, Addie (author), Groß, C. (author), de Ridder, D. (author), Reinders, M.J.T. (author), Groenen, Martien A.M. (author)Background: Deleterious genetic variation can increase in frequency as a result of mutations, genetic drift, and genetic hitchhiking. Although individual effects are often small, the cumulative effect of deleterious genetic variation can impact population fitness substantially. In this study, we examined the genome of commercial purebred chicken...journal article 2018
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Groß, C. (author), de Ridder, D. (author), Reinders, M.J.T. (author)Background: Predicting the deleteriousness of observed genomic variants has taken a step forward with the introduction of the Combined Annotation Dependent Depletion (CADD) approach, which trains a classifier on the wealth of available human genomic information. This raises the question whether it can be done with less data for non-human...journal article 2018