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

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.

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Publication Details

Journal
Nature Biotechnology
Published
2026-01-05
DOI
https://doi.org/10.1038/s41587-025-02950-z
Citations
1
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
22.24
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article

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

Zuzhi Jiang, Leor S. Weinberger, Zev J. Gartner, Matt Thomson et al.
1 citations
Nature Biotechnology
Single-cell and spatial transcriptomics
22.24
article

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

Zuzhi Jiang, Leor S. Weinberger, Zev J. Gartner, Matt Thomson, Qin Zhu, Binyamin Zuckerman
article en
1 citations

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.

Nature Biotechnology
California Institute of Technology (US), University of Miami (US), University of California, San Francisco (US), Autonomous Solutions (United States) (US), Chan Zuckerberg Initiative (United States) (US), University of San Francisco (US)
Openalex Percentile: Top 3%
Single-cell and spatial transcriptomics
22.24
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