TissueFormer: a neural network for labeling tissue from grouped single-cell RNA profiles

Benjamin, Ari S, Zador, Anthony (August 2025) TissueFormer: a neural network for labeling tissue from grouped single-cell RNA profiles. bioRxiv. ISSN 2692-8205 (Public Dataset) (Submitted)

PDF 10.1101.2025.08.17.670735.pdf - Submitted Version Available under License Creative Commons Attribution. Download (12MB)

Abstract

Single-cell RNA sequencing technologies have enabled unprecedented insights into gene expression and are poised to transform clinical diagnostics. At present, most computational approaches for interpreting single-cell data operate at the level of individual cells, predicting labels or properties based on isolated transcriptomic profiles. This approach overlooks a key class of signals: the composition of cells within a sample or defined population. Such signals are often critical for inferring tissue identity, disease state, or other sample-level phenotypes. To address this limitation, we introduce TissueFormer, a Transformer-based neural network that analyzes groups of single-cell RNA profiles to infer population-level labels while retaining single-cell resolution. Applied to predict the cortical area of groups of cells sampled from spatial transcriptomic data from mouse brains, TissueFormer outperformed both single-cell foundation models and machine learning methods applied to pseudobulk and cell type composition. This higher performance enables the automated construction of high-resolution brain region maps in individual animals directly from spatial transcriptomic data. More broadly, TissueFormer provides a framework for predicting any population-level phenotypes which are influenced by cellular diversity and tissue-level organization.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > tissues types and functions > neural networks neurobiology neurobiology > neuroscience organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Zador, Anthony M. Benjamin, Ari
Communities:	CSHL labs > Zador lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	19 August 2025
Date Deposited:	22 Sep 2025 18:18
Last Modified:	22 Sep 2025 18:18
PMCID:	PMC12393424
Related URLs:	Publisher
Dataset ID:	https://github.com/ZadorLaboratory
URI:	https://repository.cshl.edu/id/eprint/41966

Actions (login required)

Administrator's edit/view item