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Quon, J.

Publications and source records attributed to Quon, J..

4 recordsLinked to original sources

SCALPEL: A pipeline for processing large-scale spatial transcriptomics data

Spatial transcriptomics enables the precise mapping of gene expression patterns within tissue architecture, offering unprecedented insights into cellular interactions, tissue heterogeneity, and disease pathology that are unattainable with traditional transcriptomic approaches. We present a tool for processing spatial transcriptomics data, SCALPEL (Spatial Cell Analysis, Labeling, Processing, and Expression Linking). SCALPEL is specifically designed to support the analysis of large, atlas-level datasets. Our new workflow features advanced 3D segmentation optimized for dense and heterogeneous tissues, refined filtering criteria, and transcriptome-based doublet detection to remove low-quality or artifactual cells. Cell type label transfer from existing taxonomies is further improved through updated filtering thresholds. Spatial domain detection is incorporated to capture local transcriptomic organization, and tissue sections are registered to the Allen Mouse Brain Common Coordinate Framework version 3 (CCFv3) for precise anatomical alignment. Genome-wide expression imputation from single-cell RNA-sequencing (scRNAseq) further enriches the dataset. Crucially, we benchmark the performance of this updated pipeline against a previously published version of our whole-mouse-brain (WMB) dataset (Yao et al., 2023b), demonstrating substantial improvements in cell number, expression profile clarity, and spatial registration. These advances provide a robust foundation for downstream spatial analyses and set a new standard for large-scale spatial transcriptomics studies.

bioinformatics↗

A cross-species spatial transcriptomic atlas of the human and non-human primate basal ganglia

The basal ganglia are interconnected subcortical nuclei with complex topographical organization that orchestrate goal-directed behaviors and are implicated in neurodegenerative movement disorders. We generated a cellular-resolution, spatial transcriptomic atlas of the basal ganglia in human, rhesus macaque, and common marmoset, sampling over one million cells in each species. By integrating spatial data with a cross-species, consensus snRNA-seq cell type taxonomy, this atlas reveals conserved principles of molecular organization within and across structures. The cellular architecture is complex but highly stereotyped, with gene expression gradients superimposed onto discrete compartments. Extensive spatial sampling illuminates 3D gradients of molecular organization in the striatum and reveals cell type-specific core and shell compartments in the primate internal globus pallidus, which is conserved with mouse. This unified, cross-species spatial transcriptomic atlas will be a foundational resource for characterizing the molecular and functional organization of the basal ganglia and their roles in health and disease.

neuroscience↗

Epilogos: information-theoretic navigation of multi-tissue functional genomic annotations

Functional genomics data, such as chromatin state maps, provide critical insights into biological processes, but are hard to navigate and interpret. We present Epilogos to address this challenge by offering a simple information-theoretic framework for large-scale visualization, navigation and interpretation of functional genomics annotations, and apply it to over 2,000 genome-wide chromatin state maps in human and mouse. We construct intuitive visualizations of multi-tissue chromatin state maps, prioritize salient genomic regions, identify group-wise differential regions, and enable rapid similarity search given a region of interest. To facilitate usability, we provide a purpose-built web-based browser interface (http://epilogos.net) alongside open-source software for community access and adoption.

genomics↗

MerQuaCo: a computational tool for quality control in image-based spatial transcriptomics

Image-based spatial transcriptomics platforms are powerful tools often used to identify cell populations and describe gene expression in intact tissue. Spatial experiments return large, high-dimensional datasets and several open-source software packages are available to facilitate analysis and visualization. The outputs of spatial transcriptomics platforms are typically imperfect. For example, local variations in transcript detection probability are common. Software tools to characterize imperfections and their impact on downstream analyses are lacking so the data quality is assessed manually, a laborious and often a subjective process. Here we describe imperfections in a dataset of 641 fresh-frozen adult mouse brain sections collected using the Vizgen MERSCOPE. Common imperfections included the local loss of tissue from the section, tissue outside the imaging volume due to detachment from the coverslip, transcripts missing due to dropped images, varying detection probability through space, and differences in transcript detection probability between experiments. We describe the incidence of each imperfection and the likely impact on the accuracy of cell type labels. We develop MerQuaCo, open-source code that detects and quantifies imperfections without user input, facilitating the selection of sections for further analysis with existing packages. Together, our results and MerQuaCo facilitate rigorous, objective assessment of the quality of spatial transcriptomics results.

bioinformatics↗