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Purkerson, J. M.

Publications and source records attributed to Purkerson, J. M..

5 recordsLinked to original sources

Reproducible-by-design: Romics Processor, a FAIR ecosystem for multi-omics and spatial-omics analysis

Multi-omics and spatial-omics technologies are exploding in use, producing increasingly complex datasets. Existing bioinformatics tools are developing rapidly but fail to fully enforce the FAIR principles, leaving the field vulnerable to escalating issues in computational reproducibility. Here, we introduce a reproducible-by-design paradigm represented in an omics data processing package, RomicsProcessor. At its core, the "Romics_object", which is a self-contained digital artifact that encapsulates the full history of the data from the original data to the fully processed state, capturing the details of the transformative steps and the required dependencies. This architecture ensures that computational workflows are fully portable and reproducible. In this manuscript, we demonstrate RomicProcessors computational capabilities and scalability on diverse datasets, including bulk proteomics, large-scale multiplexed immunofluorescence, and multi-batch mass spectrometry imaging. Providing a robust framework for truly FAIR Data Principles-based analysis, RomicsProcessor is a blueprint for the next generation of reproducible bioinformatics tools that can dramatically accelerate discovery in multi-omics biology in the era of artificial intelligence.

bioinformatics↗

Exploring endothelial cell environments across organs in spatially resolved omics data

Endothelial cells are ubiquitously present in the human body and line the luminal surface of blood and lymphatic vessels. The oxygen-dependence of cells impacts their proximity to blood vessels, and consequently, to endothelial cells depending on their functional properties and priorities. This paper presents cell-to-nearest-endothelial-cell distance distributions for various cell types using 399 spatially resolved omics datasets from 14 studies comprising 12 tissue types with a total of 47,349,496 cells. Additionally, we developed an open-source web-based interactive tool, Cell Distance Explorer, that allows researchers to interactively visualize cell graphs and linkages in 2D and 3D datasets. Finally, we present a hierarchical neighborhood analysis focused on the endothelial cell neighborhoods in small and large intestine datasets. This paper provides an open-access resource (datasets, tools, and analyses) to characterize and compare cell distances and cell neighborhoods in spatially resolved omics data.

bioinformatics↗

A Multimodal Spatial and Epigenomic Atlas of Human Adult Lung Topography

Developing high-resolution reference maps of disease-susceptible spatial niches is a critical step to mitigating the profound effects of lung disease. Here, we present an integrated multimodal single-nucleus human lung atlas (snHLA) profiling 746,047 nuclei from 49 mapped lung blocks spanning clinically relevant distal airways, alveoli, and interstitium across 11 healthy adults. Integrating snRNA-seq and SNARE-seq2, which co-assays chromatin accessibility and gene expression from the same nucleus, we resolved 70 molecularly distinct populations and captured 332,846 accessible chromatin regions, nominating new transcriptional regulators of human lung cell diversity. Spatial transcriptomics using MERFISH mapped 25 cell populations across 7 structural neighborhoods and multiplexed immunofluorescence localized cell subtypes and distal airway-defining protein markers, expanding and validating distinct lung structure-specific cell populations. This open access snHLA and companion Cell Type and Marker Gene Dictionary with anatomically aligned nomenclature delivers a foundational resource at an unprecedented resolution to interrogate the origins of lung pathophysiology.

cell biology↗

Three Dimensional Multiscalar Neurovascular Nephron Connectivity Map of the Human Kidney Across the Lifespan

The human kidney is a vital organ with a remarkable ability to coordinate the activity of up to a million nephrons, its main functional tissue unit (FTU), and maintain homeostasis. We developed tissue processing and analytical methods to construct a 3D map of neurovascular nephron connectivity of the human kidney and glean insights into how this structural organization enables coordination of various functions of the nephron, such as glomerular filtration, solute and water absorption, secretion by the tubules, and regulation of blood flow and pressure by the juxtaglomerular apparatus, in addition to how these functions change across disease and lifespans. Using light sheet fluorescence microscopy (LSFM) and morphometric analysis we discovered changes in anatomical orientation of the vascular pole, glomerular density, volume, and innervation through postnatal development and ageing. The extensive nerve network exists from cortex FTUs to medullary loop of Henle, providing connectivity within segments of the same nephron, and between separate nephrons. The nerves organize glomeruli into discreet communities (in the same network of nerves). Adjacent glomerular communities are connected to intercommunal "mother glomeruli" by nerves, a pattern repeating throughout the cortex. These neuro-nephron networks are not developed in postnatal kidneys and are disrupted in diseased kidneys (diabetic or hydronephrosis). This structural organization likely poises the entire glomerular and juxtaglomerular FTUs to synchronize responses to perturbations in fluid homeostasis, utilizing mother glomeruli as network control centers.

neuroscience↗

Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) serves experimental datasets and supports data processing, search, filtering, and visualization. The Human Reference Atlas (HRA) Portal (https://humanatlas.io) provides open access to atlas data, code, procedures, and instructional materials. Experts from more than 20 consortia are collaborating to construct the HRAs Common Coordinate Framework (CCF), knowledge graphs, and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes, and biomarkers) and to use the HRA to understand changes that occur at each of these levels with aging, disease, and other perturbations. The 6th release of the HRA v2.0 covers 36 organs with 4,499 unique anatomical structures, 1,195 cell types, and 2,089 biomarkers (e.g., genes, proteins, lipids) linked to ontologies and 2D/3D reference objects. New experimental data can be mapped into the HRA using (1) three cell type annotation tools (e.g., Azimuth) or (2) validated antibody panels (OMAPs), or (3) by registering tissue data spatially. This paper describes the HRA user stories, terminology, data formats, ontology validation, unified analysis workflows, user interfaces, instructional materials, application programming interface (APIs), flexible hybrid cloud infrastructure, and previews atlas usage applications.

bioinformatics↗