Annotation Comparison Explorer (ACE): connecting brain cell types across studies of health and Alzheimer’s Disease

Single-cell multiomic technologies have allowed unprecedented access to gene profiles of individual cells across species and organ systems, including >1000 papers focused on brain cell types alone. The Allen Institute has created foundational atlases characterizing mammalian brain cell types in the adult mouse brain and the neocortex of aged humans with and without Alzheimer’s disease (AD). With so many public cell type classifications (or ‘taxonomies’) available and many groups choosing to define their own, linking cell types and associated knowledge between studies remains a major challenge. Here, we introduce Annotation Comparison Explorer (ACE), a web application for comparing cell type assignments and other cell-based annotations (e.g., donor demographics, anatomic locations, batch variables, and quality control metrics). ACE allows filtering of cells and includes an interactive set of tools for comparing two or more taxonomy annotations alongside collected knowledge (e.g., increased abundance in disease conditions, cell type aliases, or other information about a specific cell type). We present three primary use cases for ACE. First, we demonstrate how a user can assign cell type labels from the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) taxonomy to cells from their own study and compare these cell type mappings to existing cell type assignments and cell metadata. Second, we extend this approach to ten published human AD studies which we previously reprocessed through a common data analysis pipeline. This allowed us to compare brain taxonomies across otherwise incomparable studies and identify congruent cell type abundance changes in AD, including a decrease in abundance of subsets of somatostatin interneurons. Finally, ACE includes translation tables between different mouse and human brain cell type taxonomies publicly accessible on Allen Brain Map, from initial studies in individual neocortical areas to more recent studies spanning the whole brain. ACE can be freely and publicly accessed as a web application ( https://sea-ad.shinyapps.io/ACEapp/ ) and on GitHub ( github.com/AllenInstitute/ACE ).