Thomas Höllt

Thomas Höllt
Leiden University Medical Centre | LUMC · Leiden Computational Biology Center

28.7
 · 
PhD
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Projects (2)
Project
The VAnPIRe project aims at developing visual analytics techniques for the analysis of large high-dimensional dataset. Such techniques will be used for hypothesis-generation in several domains, e.g. in population imaging studies.
Project
The unravel the role of immune subsets in intestinal pathology using a system-wide analysis approach by combining mass cytometry with computational tools
Research
Research items (76)
Article
Full-text available
To understand how the immune system works, one needs to have a clear picture of its cellular compositon and the cells’ corresponding properties and functionality. Mass cytometry is a novel technique to determine the properties of single-cells with unprecedented detail. This amount of detail allows for much finer differentiation but also comes at th...
Article
Full-text available
In recent years, dimensionality-reduction techniques have been developed and are widely used for hypothesis generation in Exploratory Data Analysis. However, these techniques are confronted with overcoming the trade-off between computation time and the quality of the provided dimensionality reduction. In this work, we address this limitation, by in...
Article
Full-text available
Single-cell analysis through mass cytometry has become an increasingly important tool for immunologists to study the immune system in health and disease. Mass cytometry creates a high-dimensional description vector for single cells by time-of-flight measurement. Recently, t-Distributed Stochastic Neighborhood Embedding (t-SNE) has emerged as one of...
Article
Full-text available
Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for the data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are limited in...
Article
Full-text available
The fetus is thought to be protected from exposure to foreign antigens, yet CD45RO⁺ T cells reside in the fetal intestine. Here we combined functional assays with mass cytometry, single-cell RNA sequencing and high-throughput T cell antigen receptor (TCR) sequencing to characterize the CD4⁺ T cell compartment in the human fetal intestine. We identi...
Article
Full-text available
The clinical benefit of immunotherapeutic approaches against cancer has been well established although complete responses are only observed in a minority of patients. Combination immunotherapy offers an attractive avenue to develop more effective cancer therapies by improving the efficacy and duration of the tumor-specific T-cell response. Here, we...
Article
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Tissue functionality is determined by the characteristics of tissue-resident cells and their interactions within their microenvironment. Imaging Mass Cytometry offers the opportunity to distinguish cell types with high precision and link them to their spatial location in intact tissues at sub-cellular resolution. This technology produces large amou...
Article
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Objective A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC. De...
Article
Hierarchical embeddings, such as HSNE, address critical visual and computational scalability issues of traditional techniques for dimensionality reduction. The improved scalability comes at the cost of the need for increased user interaction for exploration. In this paper, we provide a solution for the interactive visual Focus+Context exploration o...
Article
Full-text available
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. However, the power of CyTOF to explore the full heterogeneity of a biological sample at the single-cell level is currently limited by the number of markers me...
Article
Full-text available
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. However,...
Conference Paper
Checkpoint blockade has revived the potential of immunotherapy for cancer treatment. For optimal application and development of cancer immunotherapies, a comprehensive understanding of the antitumor immune response is required. We unraveled local and systemic immune profiles of colorectal cancer by multidimensional mass cytometric analysis of 36 im...
Article
Background Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the intestine. Studies on individual immune lineages have shown alterations in the innate and adaptive intestinal immune system implicated in IBD. However, a comprehensive analysis of the cell composition in intestinal biopsies from IBD patients across all major...
Article
Full-text available
Multi-parametric flow and mass cytometry allows exceptional high-resolution exploration of the cellular composition of the immune system. A large panel of computational tools have been developed to analyze the high-dimensional landscape of the data generated. Analysis frameworks such as FlowSOM or Cytosplore incorporate clustering and dimensionalit...
Article
Full-text available
Purpose: The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood. Experimental design: We applied high-dimensional single-cell mass cytometry (CyTOF) analysis and functional studies to analyze immune cell populations in hu...
Article
Full-text available
Auto-reactive CD8 T-cells play an important role in the destruction of pancreatic β-cells resulting in type 1 diabetes (T1D). However, the phenotype of these auto-reactive cytolytic CD8 T-cells has not yet been extensively described. We used high-dimensional mass cytometry to phenotype autoantigen- (pre-proinsulin), neoantigen- (insulin-DRIP) and v...
Data
Information of patients diagnosed with T1D. (DOCX)
Data
Detection of specific CD8 T-cells. a) Schematic overview of staining peptide-specific CD8 T-cells using HLA-class I tetramers in CyTOF2. b) HLA-A2 negative PBMCs spiked with 1% PPI-specific (panel 1), 1% INS-DRIP-specific (panel 2) and 1% CMV-specific CD8 clone (panel 3). c) Dot plots and frequencies of circulating PPI, INS-DRIP and CMV reactive CD...
Data
Distribution of CD8 T-cells derived from three T1D patients per cluster. The graph shows a heterogeneous distribution of CD8 T-cells from different patients within the clusters. The order of the clusters corresponds to the heat map in Fig 1D. (TIF)
Data
t-SNE analysis of CD8 compartment. t-SNE embedding per patient, the marker expression per patient is displayed. Markers CD8, CD3 and TCRgd used for gating, as well as the negative markers NKp44 and NKp46 are not displayed. (TIF)
Data
Heat map of three T1D patients two way clustering. Left sidebar displays specificity (red = PPI, blue = INS-Drip, green = CMV, grey = CD8 tetramer negative, middle sidebar displays patient origin (pink = patient 1, light blue = patient 2, purple = patient 3), right sidebar displays the tetramer expression (anti-PE signal). b) t-SNE maps and Jensen-...
Data
Total number of events acquired per patient. (DOCX)
Preprint
Full-text available
Elucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. Here we applied single nucleus RNA-sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhi...
Article
Full-text available
A bipartite graph is a powerful abstraction for modeling relationships between two collections. Visualizations of bipartite graphs allow users to understand the mutual relationships between the elements in the two collections, e.g., by identifying clusters of similarly connected elements. However, commonly‐used visual representations do not scale f...
Conference Paper
Full-text available
Introduction Immune checkpoint blockade has revolutionised cancer treatment. However, clinical outcomes are highly variable as only a proportion of cancer patients benefit from this treatment. To understand the mechanisms that determine responses to current immunotherapies and for the design of alternative approaches, it is crucial to characterise...
Preprint
Full-text available
The t-distributed Stochastic Neighbor Embedding (tSNE) algorithm has become in recent years one of the most used and insightful techniques for the exploratory data analysis of high-dimensional data. tSNE reveals clusters of high-dimensional data points at different scales while it requires only minimal tuning of its parameters. Despite these advant...
Preprint
Full-text available
Mass cytometry (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, however, they are time consuming, often involve a manual step, and lack reproducibility when new data is incl...
Article
Full-text available
Innate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. Although several ILC subsets have been identified, it is unknown if additional heterogeneity exists, and their differentiation pathways remain largely unclear. We applied mass cytometry to analyze ILCs in the human fetal intestine a...
Article
Full-text available
Technological advances in mass spectrometry imaging (MSI) have contributed to the growing interest in 3D-MSI. However, the large size of 3D-MSI datasets has made their efficient analysis, visualization and the identification of informative molecular patterns, computationally challenging. Hierarchical stochastic neighbor embedding (HSNE), a non-line...
Article
Full-text available
The relationship between human cytomegalovirus (HCMV) infections and accelerated immune senescence is controversial. Whereas some studies reported a CMV-associated impaired capacity to control heterologous infections at old age, other studies could not confirm this. We hypothesized that these discrepancies might relate to the variability in the inf...
Article
Full-text available
Deep neural networks are now rivaling human accuracy in several pattern recognition problems. Compared to traditional classifiers, where features are handcrafted, neural networks learn increasingly complex features directly from the data. Instead of handcrafting the features, it is now the network architecture that is manually engineered. The netwo...
Article
Full-text available
A Diffusion Tensor Imaging (DTI) group study consists of a collection of volumetric diffusion tensor datasets (i.e., an ensemble) acquired from a group of subjects. The multivariate nature of the diffusion tensor imposes challenges on the analysis and the visualization. These challenges are commonly tackled by reducing the diffusion tensors to scal...
Article
Full-text available
Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: a web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human brain t...
Article
Full-text available
Progressive Visual Analytics aims at improving the interactivity in existing analytics techniques by means of visualization as well as interaction with intermediate results. One key method for data analysis is dimensionality reduction, for example, to produce 2D embeddings that can be visualized and analyzed efficiently. t-Distributed Stochastic Ne...
Conference Paper
Full-text available
Hydrocarbon reservoir simulation models produce large amounts of heterogeneous data, combining multiple variables of different dimensionality, such as two or three-dimensional geospatial estimates with abstract estimates simulated for the complete field or different wells. In addition these simulations are nowadays often run as so-called ensemble s...
Article
Full-text available
Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We us...
Article
Full-text available
We present a novel integrated visualization system that enables the interactive visual analysis of ensemble simulations and estimates of the sea surface height and other model variables that are used for storm surge prediction. Coastal inundation, caused by hurricanes and tropical storms, poses large risks for today's societies. High-fidelity numer...
Conference Paper
Full-text available
Ocean forecasts nowadays are created by running ensemble simulations in combination with data assimilation techniques. Most of these techniques resample the ensemble members after each assimilation cycle. This means that in a time series, after resampling, every member can follow up on any of the members before resampling. Tracking behavior over ti...
Article
Full-text available
We present a novel integrated visualization system that enables interactive visual analysis of ensemble simulations of the sea surface height that is used in ocean forecasting. The position of eddies can be derived directly from the sea surface height and our visualization approach enables their interactive exploration and analysis. The behavior of...
Thesis
Full-text available
The most important resources to fulfill today's energy demands are fossil fuels, such as oil and natural gas. When exploiting hydrocarbon reservoirs, a detailed and credible model of the subsurface structures to plan the path of the borehole, is crucial in order to minimize economic and ecological risks. Before that, the placement, as well as the o...