document

Predicting cell population-specific gene expression from genomic sequence

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

Consequences and opportunities arising due to sparser single-cell RNA-seq datasets

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

scTopoGAN: unsupervised manifold alignment of single-cell data

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

Cell type matching across species using protein embeddings and transfer learning

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

Single-cell reference mapping to construct and extend cell-type hierarchies

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

Benchmarking variational AutoEncoders on cancer transcriptomics data

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

The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease

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

Correcting Differential Gene Expression Analysis for Cyto—Architectural Alterations in Substantia Nigra of Parkinson’s Disease Patients Reveals Known and Potential Novel Disease—Associated Genes and Pathways

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

scMoC: single-cell multi-omics clustering

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

Identification and characterization of two consistent osteoarthritis subtypes by transcriptome and clinical data integration

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

document

CBA: Cluster-Guided Batch Alignment for Single Cell RNA-seq

Yu, W. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)

The power of single-cell RNA sequencing (scRNA-seq) in detecting cell heterogeneity or developmental process is becoming more and more evident every day. The granularity of this knowledge is further propelled when combining two batches of scRNA-seq into a single large dataset. This strategy is however hampered by technical differences between...

journal article 2021

document

Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson’s Disease

Keo, 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

document

Single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress

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

document

Hierarchical progressive learning of cell identities in single-cell data

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

document

Cingulate networks associated with gray matter loss in Parkinson's disease show high expression of cholinergic genes in the healthy brain

Keo, D.L. (author), Dzyubachyk, Oleh (author), van der Grond, Jeroen (author), Hafkemeijer, Anne (author), van de Berg, Wilma D.J. (author), van Hilten, Jacobus J. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)

Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance across a population. We examined the transcriptomic signature of such anatomical networks in the healthy brain using postmortem microarray data from the Allen Human Brain Atlas. A previous study revealed that a posterior...

journal article 2021

document

Differential analysis of binarized single-cell RNA sequencing data captures biological variation

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

document

Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

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

document

SpaGE: Spatial Gene Enhancement using scRNA-seq

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

document

Predicting Cell Populations in Single Cell Mass Cytometry Data

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

document

A comparison of automatic cell identification methods for single-cell RNA sequencing data

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