cellNexus: Quality control, annotation, aggregation and analytical layers for the Human Cell Atlas data

Abstract Large-scale single-cell atlases such as the Human Cell Atlas have transformed our understanding of human biology. Yet, the lack of a robust framework that standardises quality control, expands cellular annotation, and adds normalisation and analytical layers, limits multi-study analyses and the usefulness of this resource. Here we present cellNexus, a comprehensive resource that enhances the Human Cell Atlas collection into analysis-ready data by linking quality control layers, metadata enrichment, expression normalisation, analysis and data aggregation. These enhancements enable robust large-scale statistical modelling across studies, exemplified here by a multi-tissue map of immune cell communication during ageing. All harmonised layers are accessible via a public web interface and with R and Python APIs. By providing continuous integration with CELLxGENE releases, cellNexus transforms large cell atlas corpora into an accessible, reproducible, interoperable foundation for large-scale biological discovery and the next generation of single-cell foundation models.