- document
-
Zheng, Dongxu (author), Wondergem, Annelot (author), Kloet, Susan (author), Willemsen, Iris (author), Balog, Judit (author), Tapscott, Stephen J. (author), Mahfouz, A.M.E.T.A. (author), Van Den Heuvel, Anita (author), Van Der Maarel, Silvère M. (author)The sporadic nature of DUX4 expression in FSHD muscle challenges comparative transcriptome analyses between FSHD and control samples. A variety of DUX4 and FSHD-associated transcriptional changes have been identified, but bulk RNA-seq strategies prohibit comprehensive analysis of their spatiotemporal relation, interdependence and role in the...journal article 2024
- document
-
Berkhout, J. B. (author), Poormoghadam, D. (author), Yi, C. (author), Kalsbeek, A. (author), Meijer, O. C. (author), Mahfouz, A.M.E.T.A. (author)The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signaling, outflow of the autonomic nervous system, and projections to other brain areas. In the past years, single-cell datasets of the hypothalamus have contributed immensely to the current...journal article 2024
- document
-
Michielsen, L.C.M. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Most regulatory elements, especially enhancer sequences, are cell population-specific. One could even argue that a distinct set of regulatory elements is what defines a cell population. However, discovering which non-coding regions of the DNA are essential in which context, and as a result, which genes are expressed, is a difficult task. Some...journal article 2024
- document
-
Bouland, G.A. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)With the number of cells measured in single-cell RNA sequencing (scRNA-seq) datasets increasing exponentially and concurrent increased sparsity due to more zero counts being measured for many genes, we demonstrate here that downstream analyses on binary-based gene expression give similar results as count-based analyses. Moreover, a binary...journal article 2023
- document
-
Habets, Philippe C. (author), Kalafatakis, Konstantinos (author), Dzyubachyk, O. (author), van der Werff, Steven J.A. (author), Keo, D.L. (author), Thakrar, Jamini (author), Mahfouz, A.M.E.T.A. (author), Pereira, Alberto M. (author), Russell, Georgina M. (author)The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and...journal article 2023
- document
-
Singh, A. (author), Biharie, K. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author), Abdelaal, T.R.M. (author)Motivation: Single-cell technologies allow deep characterization of different molecular aspects of cells. Integrating these modalities provides a comprehensive view of cellular identity. Current integration methods rely on overlapping features or cells to link datasets measuring different modalities, limiting their application to experiments...journal article 2023
- document
-
Biharie, K. (author), Michielsen, L.C.M. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Motivation: Knowing the relation between cell types is crucial for translating experimental results from mice to humans. Establishing cell type matches, however, is hindered by the biological differences between the species. A substantial amount of evolutionary information between genes that could be used to align the species is discarded by...journal article 2023
- document
-
Novella-Rausell, Claudio (author), Grudniewska, Magda (author), Peters, Dorien J.M. (author), Mahfouz, A.M.E.T.A. (author)The kidney's cellular diversity is on par with its physiological intricacy; yet identifying cell populations and their markers remains challenging. Here, we created a comprehensive atlas of the healthy adult mouse kidney (MKA: Mouse Kidney Atlas) by integrating 140.000 cells and nuclei from 59 publicly available single-cell and single-nuclei...journal article 2023
- document
-
Heezen, L. G.M. (author), Abdelaal, T.R.M. (author), van Putten, M. (author), Aartsma-Rus, A. (author), Mahfouz, A.M.E.T.A. (author), Spitali, P. (author)Duchenne muscular dystrophy is caused by mutations in the DMD gene, leading to lack of dystrophin. Chronic muscle damage eventually leads to histological alterations in skeletal muscles. The identification of genes and cell types driving tissue remodeling is a key step to developing effective therapies. Here we use spatial transcriptomics in...journal article 2023
- document
-
Michielsen, L.C.M. (author), Lotfollahi, Mohammad (author), Strobl, Daniel (author), Sikkema, Lisa (author), Reinders, M.J.T. (author), Theis, Fabian J. (author), Mahfouz, A.M.E.T.A. (author)Single-cell genomics is now producing an ever-increasing amount of datasets that, when integrated, could provide large-scale reference atlases of tissue in health and disease. Such large-scale atlases increase the scale and generalizability of analyses and enable combining knowledge generated by individual studies. Specifically, individual...journal article 2023
- document
-
Eltager, M.A.M.E. (author), Abdelaal, T.R.M. (author), Charrout, M. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author), Makrodimitris, S. (author)Deep generative models, such as variational autoencoders (VAE), have gained increasing attention in computational biology due to their ability to capture complex data manifolds which subsequently can be used to achieve better performance in downstream tasks, such as cancer type prediction or subtyping of cancer. However, these models are...journal article 2023
- document
-
Morgana, Florencia (author), Opstelten, Rianne (author), Slot, Manon C. (author), Scott, Andrew M. (author), van Lier, René A.W. (author), Blom, Bianca (author), Mahfouz, A.M.E.T.A. (author), Amsen, Derk (author)CD4+CD25+FOXP3+ regulatory T (Treg) cells control immunological tolerance. Treg cells are generated in the thymus (tTreg) or in the periphery. Their superior lineage fidelity makes tTregs the preferred cell type for adoptive cell therapy (ACT). How human tTreg cells develop is incompletely understood. By combining single-cell transcriptomics...journal article 2022
- document
-
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
- document
-
Dieckman, Tessa (author), Schreurs, Mette (author), Mahfouz, A.M.E.T.A. (author), Kooy-Winkelaar, Yvonne (author), Neefjes-Borst, Andra (author), Bouma, Gerd (author), Koning, Frits (author)Background & Aims: Refractory celiac disease type II (RCDII) is a rare indolent lymphoma in the small intestine characterized by a clonally expanded intraepithelial intracellular CD3<sup>+</sup>surfaceCD3<sup>-</sup>CD7<sup>+</sup>CD56<sup>-</sup> aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at...journal article 2022
- document
-
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
- document
-
van Unen, Vincent (author), Ouboter, Laura F. (author), Li, Na (author), Schreurs, Mette (author), Abdelaal, T.R.M. (author), Kooy-Winkelaar, Yvonne (author), Beyrend, Guillaume (author), Höllt, T. (author), Maljaars, P. W.Jeroen (author), Mearin, M. Luisa (author), Mahfouz, A.M.E.T.A. (author), Witte, Anne M.C. (author), Clemens, Cornelis H.M. (author), Abraham, Sunje (author), Escher, Johanna C. (author), Lelieveldt, B.P.F. (author), Pascutti, M. Fernanda (author), van der Meulen – de Jong, Andrea E. (author), Koning, Frits (author)Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high...journal article 2022
- document
-
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
- document
-
Eltager, M.A.M.E. (author), Abdelaal, T.R.M. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Motivation: Single-cell multi-omics assays simultaneously measure different molecular features from the same cell. A key question is how to benefit from the complementary data available and perform cross-modal clustering of cells. Results: We propose Single-Cell Multi-omics Clustering (scMoC), an approach to identify cell clusters from data...journal article 2022
- document
-
Wang, Gangqi (author), Heijs, Bram (author), Kostidis, Sarantos (author), Mahfouz, A.M.E.T.A. (author), Rietjens, Rosalie G.J. (author), Bijkerk, Roel (author), Koudijs, Angela (author), van der Pluijm, Loïs A.K. (author), van den Berg, Cathelijne W. (author)A common drawback of metabolic analyses of complex biological samples is the inability to consider cell-to-cell heterogeneity in the context of an organ or tissue. To overcome this limitation, we present an advanced high-spatial-resolution metabolomics approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI...journal article 2022
- document
-
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