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Biology subjects

Gunz, S.

Publications and source records attributed to Gunz, S..

7 recordsLinked to original sources

Building computational benchmarks: an Omnibenchmark reimplementation of a single-cell preprocessing pipeline evaluation

In the past few years, we have seen a veritable surge in single-cell (e.g., RNA sequencing) techniques and datasets, enabling increasingly detailed characterization of cellular heterogeneity across tissues and conditions. This surge in single-cell techniques has been complemented by a large number of analysis frameworks and pipelines, and a large parameter space and researcher degrees of freedom to use them. Many neutral benchmarks have been presented for various computational tasks, but most make design decisions that render them incompatible with each other, e.g., different datasets and metrics, or parameter sets used. In this work, we showcase a recently developed framework, Omnibenchmark, to build reproducible, extensible and standardized method comparisons. This not only facilitates the broad investigation of pipelines used in single-cell data analysis, but also highlights how the process of building benchmarks can be streamlined and unified. We do this as an initial proof-of-principle for an arms-length benchmark that evaluates five single-cell RNA sequencing pipelines (filtering to normalization to dimensionality reduction to clustering) on three datasets. This standardization enables benchmarks to be easily extended in several directions, including broader parameter sweeps, comparisons across software versions and architectures, isolation of pipeline steps, and integration of additional pipelines, datasets, and metrics.

bioinformatics↗

Differential co-localisation analysis of multi-sample and multi-condition experiments with spatialFDA

Advances in spatial omics data generation have led to an explosion in new datasets that record the spatial location of transcripts and proteins. However, challenges remain in the analysis of spatial omics data. One important analysis is differential cellular co-localisation (CCoL): the quantification of the clustering, or spacing, of one or more cell types across multiple conditions. Our framework spatialFDA combines methodology from spatial statistics with functional data analysis to accurately quantify and test for differences between conditions in CCoL across spatial scales. Using two simulation studies, we show that spatialFDA performs well in controlled settings. Furthermore, spatialFDA recovers known biological processes in type-1 diabetes and adds insights about the CCoL strength in space. spatialFDA is readily available as an open-source Bioconductor R package.

bioinformatics↗

Orchestrating Spatial Transcriptomics Analysis with Bioconductor

Spatial transcriptomics technologies provide spatially-resolved measurements of gene expression through assays that can either target selected genes or capture transcriptome-wide expression profiles. The complexity and variability of these technologies and their associated data necessitate multi-step workflows integrating diverse computational methods and software packages. We provide a freely accessible, open-source, continuously updated and tested online book containing reproducible code examples, datasets, and discussion about data analysis workflows for spatial omics data using Bioconductor in R, including interoperability with Python.

bioinformatics↗

Analysis of anatomical multi-cellular structures from spatial omics data using sosta

Spatial omics technologies enable high-resolution, large-scale quantification of molecular features while preserving the spatial context within tissues. Existing analysis methods largely focus on spatial arrangements of single cells, whereas biological function often emerges from multicellular arrangements. Here, we introduce structure-based analysis of spatial omics data, which focuses on the direct analysis of multicellular, anatomical structures. We illustrate this type of analysis using two publicly available datasets and provide sosta, an open-source Bioconductor package for broad community use.

bioinformatics↗

A transcriptional map of human tonsil architecture:beyond the sum of (single cell) parts

The tonsil is a highly compartmentalized organ in which different microanatomical structures orchestrate designated (immune) functions. We use this already well-studied tissue to survey spatial molecular imaging data (CosMx SMI) for studying immune responses in native tissue context; and, to demonstrate the advantages of SMI for faithfully recapitulating cellular composition in direct comparison with single-cell RNA sequencing. While SMI data still poses many analytical challenges and lacks standardization, we established a versatile analysis pipeline focused on the profitable particularities of these data: considering organization (microenvironment), interactions (signaling), and function (higher-order structures) across scales. Specifically, we resolve ~ 2M cells into 52 subpopulations across immune and, in particular, structural compartments. Various spatial niches partition tonsillar tissue into architecturally and functionally distinct regions, which we characterize through cell-cell colocalization and communication analyses, while performing various non-standard analyses at the level of spatial features. These topological readouts may help elucidate where certain immunological processes occur (e.g., class switch recombination); and, where signaling pathways are active (e.g., TNF and galectin, which have been implicated in diverse lymphomas). In all, we provide an analytical framework for Spatial Immunology, and showcase alternative views that such techniques and concomitant computational approaches can bring on tissue composition and architecture.

immunology↗

Beyond benchmarking: an expert-guided consensus approach to spatially aware clustering

Spatial omics technologies have revolutionized the study of tissue architecture and cellular heterogeneity by integrating molecular profiles with spatial localization. In spatially resolved transcriptomics, delineating higher-order anatomical structures is critical for understanding how cellular organization affects tissue and organ function. Since 2020, more than 50 spatially aware clustering (SAC) methods have been developed for this purpose. However, the reliability of current benchmarks is undermined by their narrow focus on Visium and brain tissue datasets, as well as incorrect interpretation of manual annotation as ground truth. Here, we present SACCELERATOR, a community-driven, extensible framework that standardizes data formatting, method integration, and metric evaluation, and is designed to rapidly incorporate new methods and datasets. SACCELERATOR currently includes 22 SAC methods applied to 15 datasets spanning 9 technologies and diverse tissue types. Our analysis revealed substantial limitations in the generalizability and reproducibility of SAC methods across tissues and platforms. We also demonstrate that anatomical labels commonly used as ground truths are often biased, potentially error-prone, and, in some cases, unsuitable for benchmarking efforts. Rather than scoring and comparing methods, we propose a consensus-guided workflow that aggregates clustering results to generate consensus representations. Descriptive spatial metrics highlight areas of high entropy where method disagreement is highest, enabling targeted feedback for tissue experts. Applied to brain and cancer datasets, this approach uncovered biologically meaningful patterns overlooked by individual methods and manual annotations. Our results underscore the need for iterative, expert-in-the-loop analysis and reveal that traditional evaluation metrics do not always capture the subjective qualities of results. By improving tissue annotation and addressing key benchmarking limitations, SACCELERATOR provides a robust foundation for advancing spatial omics research.

genomics↗

The super-enhancer landscape reflects molecular subgroups of adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland with generally very unfavourable outcome. Two molecular subgroups, C1A and C1B, have been previously identified with a significant association with patient survival. In this work, we study chromatin state organization characterized by histone modifications using ChIP-sequencing in adult ACC. We describe the super-enhancer landscape of ACC, characterized by H3K27ac, and identify super-enhancer regulated genes that play a significant role in tumorigenesis. We show that the super-enhancer landscape reflects differences between the molecular sub-groups C1A and C1B and identify networks of master transcription factors mirroring these differences. Additionally, we study the effects of molecules THZ1 and JQ1 previously reported to affect super-enhancer-driven gene expression in ACC cell lines. Our results reveal that the landscape of histone modifications in ACC is linked to its molecular subgroups and thus provide the groundwork for future analysis of epigenetic reprogramming in ACC.

cancer biology↗