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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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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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Khatri, I. (author), Diks, Annieck M. (author), van den Akker, E.B. (author), Oosten, Liesbeth E. M. (author), Zwaginga, Jaap Jan (author), Reinders, M.J.T. (author), van Dongen, Jacques J. M. (author), Berkowska, Magdalena A. (author)To mount an adequate immune response against pathogens, stepwise mutation and selection processes are crucial functions of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of the single-cell transcriptome as well as the B...journal article 2021
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Bouland, G.A. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Single-cell RNA sequencing data is characterized by a large number of zero counts, yet there is growing evidence that these zeros reflect biological variation rather than technical artifacts. We propose to use binarized expression profiles to identify the effects of biological variation in single-cell RNA sequencing data. Using 16 publicly...journal article 2021
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Reinders, K.J. (author), Hanssen, R.F. (author), van Leijen, F.J. (author), Korff, M. (author)In this work, we investigate if, when, and how satellite InSAR can be used for evaluating surface settlements that occur during shield tunnelling in soft soil areas. We evaluate the applicability of InSAR prior, during, and after tunnel construction. Special emphasis is placed on the influence of the InSAR phase ambiguities in relation to short...journal article 2021
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Holstege, H. (author), Reinders, M.J.T. (author)Genetic association studies are frequently used to study the genetic basis of numerous human phenotypes. However, the rapid interrogation of how well a certain genomic region associates across traits as well as the interpretation of genetic associations is often complex and requires the integration of multiple sources of annotation, which...journal article 2021
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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), Huisman, Martijn (author), Reinders, M.J.T. (author), Holstege, H. (author)Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with...journal article 2021
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Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson’s DiseaseKeo, D.L. (author), Dzyubachyk, Oleh (author), Van Der Grond, Jeroen (author), van Hilten, Jacobus J. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Cortical atrophy is a common manifestation in Parkinson’s disease (PD), particularly in advanced stages of the disease. To elucidate the molecular underpinnings of cortical thickness changes in PD, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and patterns of cortical thickness...journal article 2021
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Ju, Jie (author), Wismans, Leonoor V. (author), Mustafa, Dana A.M. (author), Reinders, M.J.T. (author), van Eijck, Casper H.J. (author), Li, Yunlei (author)A major challenge for treating patients with pancreatic ductal adenocarcinoma (PDAC) is the unpredictability of their prognoses due to high heterogeneity. We present Multi-Omics DEep Learning for Prognosis-correlated subtyping (MODEL-P) to identify PDAC subtypes and to predict prognoses of new patients. MODEL-P was trained on autoencoder...journal article 2021
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Khatri, I. (author), Berkowska, Magdalena A. (author), van den Akker, E.B. (author), Teodosio, Cristina (author), Reinders, M.J.T. (author), van Dongen, Jacques J. M. (author)Immunoglobulin (IG) loci harbor inter-individual allelic variants in many different germline IG variable, diversity and joining genes of the IG heavy (IGH), kappa (IGK) and lambda (IGL) loci, which together form the genetic basis of the highly diverse antigen-specific B-cell receptors. These allelic variants can be shared between or be...journal article 2021
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Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodiesvan der Lee, S.J. (author), van Steenoven, Inger (author), van de Beek, Marleen (author), Tesi, N. (author), Jansen, Iris E. (author), van Schoor, N.M. (author), Reinders, M.J.T. (author), Huisman, Martijn (author), Scheltens, Philip (author)Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. Objective: We tested if genetic variants in part explain the heterogeneity in DLB. Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and...journal article 2021
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Reus, Lianne M. (author), Jansen, Iris E. (author), van Rooij, Jeroen (author), van Schoor, Natasja M. (author), Tesi, N. (author), Reinders, M.J.T. (author), Huisman, M.A. (author), van der Lugt, Aad (author), van der Lee, Sven J. (author)Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants...journal article 2021
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Tesi, N. (author), Hulsman, M. (author), van der Lee, S.J. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, Natasja M. (author), Scheltens, Philip (author), Reinders, M.J.T. (author), Holstege, H. (author)Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-nucleotide-polymorphisms (SNPs) in...journal article 2021
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- Smit, J. M. (author), van Genderen, M. E. (author), Reinders, M.J.T. (author), Gommers, D. A.M.P.J. (author), Krijthe, J.H. (author), Van Bommel, J. (author) journal article 2021
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- Khatri, Indu (author), Berkowska, Magdalena A. (author), van den Akker, E.B. (author), Teodosio, Cristina (author), Reinders, M.J.T. (author), van Dongen, Jacques J.M. (author) journal article 2021
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van den Bent, Irene (author), Makrodimitris, S. (author), Reinders, M.J.T. (author)Computationally annotating proteins with a molecular function is a difficult problem that is made even harder due to the limited amount of available labeled protein training data. Unsupervised protein embeddings partly circumvent this limitation by learning a universal protein representation from many unlabeled sequences. Such embeddings...journal article 2021
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Groen, Nathalie (author), Leenders, Floris (author), Mahfouz, A.M.E.T.A. (author), Munoz-Garcia, Amadeo (author), Muraro, Mauro J. (author), de Graaf, Natascha (author), Rabelink, Ton J. (author), Hoeben, Rob (author), Reinders, M.J.T. (author)The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet...journal article 2021
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Michielsen, L.C.M. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Supervised methods are increasingly used to identify cell populations in single-cell data. Yet, current methods are limited in their ability to learn from multiple datasets simultaneously, are hampered by the annotation of datasets at different resolutions, and do not preserve annotations when retrained on new datasets. The latter point is...journal article 2021
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Derks, Martijn F.L. (author), Groß, C. (author), Lopes, Marcos S. (author), Reinders, M.J.T. (author), Bosse, Mirte (author), Gjuvsland, Arne B. (author), de Ridder, Dick (author), Megens, Hendrik-Jan (author), Groenen, Martien A.M. (author)The genotype-phenotype link is a major research topic in the life sciences but remains highly complex to disentangle. Part of the complexity arises from the number of genes contributing to the observed phenotype. Despite the vast increase of molecular data, pinpointing the causal variant underlying a phenotype of interest is still challenging...journal article 2021
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Coutinho de Almeida, Rodrigo (author), Mahfouz, A.M.E.T.A. (author), Mei, Hailiang (author), Houtman, Evelyn (author), den Hollander, Wouter (author), Soul, Jamie (author), Suchiman, Eka (author), Nelissen, R.G.H.H. (author), Reinders, M.J.T. (author)OBJECTIVE: To identify OA subtypes based on cartilage transcriptomic data in cartilage tissue and characterize their underlying pathophysiological processes and/or clinically relevant characteristics. METHODS: This study includes n = 66 primary OA patients (41 knees and 25 hips), who underwent a joint replacement surgery, from which...journal article 2021