Revealing a coherent cell-state landscape across single-cell datasets with CONCORD

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Authors: Qin Zhu, Zuzhi Jiang, Binyamin Zuckerman, Leor S. Weinberger, Matt Thomson, Zev J. Gartner
Cited by: 5
References: 72

Abstract

Revealing the underlying cell-state landscape from single-cell data requires overcoming the critical obstacles of batch integration, denoising and dimensionality reduction. Here we present CONCORD, a unified framework that simultaneously addresses these challenges within a single self-supervised model. At its core, CONCORD implements a probabilistic sampling strategy that corrects batch effects through dataset-aware sampling and enhances biological resolution through hard-negative sampling. Using only a minimalist neural network with a single hidden layer and contrastive learning, CONCORD surpasses state-of-the-art performance without relying on deep architectures, auxiliary losses or external supervision. It seamlessly integrates data across batches, technologies and even species to generate high-resolution cell atlases. The resulting latent representations are denoised and biologically meaningful, capturing gene coexpression programs, revealing detailed lineage trajectories and preserving both local geometric relationships and global topological structures. We demonstrate CONCORD's broad applicability across diverse datasets, establishing it as a general-purpose framework for learning unified, high-fidelity representations of cellular identity and dynamics.

Fields of Study & Subjects

Single-cell and spatial transcriptomics Cell Image Analysis Techniques Gene Regulatory Network Analysis

Publication details

Journal / source
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Publication date
5 January 2026
Language
EN