A Single-cell and Spatial RNA-seq Database for Alzheimer’s Disease (ssREAD)

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative malady predominantly affecting the elderly and exhibits its debilitating effects on a dementia-prone population. Recently, the advent of innovative technologies, such as single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST), has reformed our investigative approaches toward comprehending AD’s neuropathological intricacies and underpinning regulatory mechanisms, encompassing sub-cellular, cellular, and spatial dimensions. In light of the overwhelming proliferation of single-cell and ST data associated with AD, the imperative for a comprehensive, user-friendly database that addresses the scientific community’s analytical demands has never been more paramount. Introduced initially in 2020, scREAD presented itself as a pioneering repository that systematized publicly available scRNA-seq and snRNA-seq datasets derived from post-mortem human brain tissues and mouse models mirroring AD pathology. Here, we introduce ssREAD, a substantial upgrade over scREAD, enriching the platform with a broader spectrum of datasets, an optimized analytical pipeline, and enhanced usability and visibility. Specifically, ssREAD amalgamates an impressive portfolio of over 189 datasets extracted from 35 distinct AD-related scRNA-seq and snRNA-seq studies, encompassing a staggering 2,572,355 cells. In addition, we have diligently curated and archived 300 ST datasets, originating from 12 human and mouse brain studies, which include two focused on AD and ten control studies. Every dataset within our repository is meticulously annotated, bearing critical identifiers including species, gender, brain region, disease/control status, age, and AD stages. Besides the collection of above datasets in ssREAD, it delivers an exhaustive analysis suite offering cell clustering and annotation, inference of differentially expressed and spatially variable genes, identification of cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis of ST and scRNA-seq & snRNA-seq data from public domains. All these resources are freely accessible through a user-friendly, consolidated web portal available athttps://bmblx.bmi.osumc.edu/ssread/.

A systematic overview of single-cell transcriptomics databases, their use cases, and limitations

“…While SC2disease represents a pioneering effort in disease-specific gene expression profiling, there is also a growing need for more specific databases dedicated to the disease of interest. To address this, databases like SC2sepsis ( Li et al, 2022 ), ssREAD ( Wang C. et al, 2023 ), and SCovid ( Qi et al, 2022 ) have emerged, focusing on individual diseases such as sepsis, Alzheimer’s, and COVID-19, respectively. These databases aim to provide a more granular and disease-specific view of gene expression patterns, enhancing our understanding of disease mechanisms and potential therapeutic targets.…”