ChromFound: Towards A Universal Foundation Model for Single-Cell Chromatin Accessibility Data

Fuente: arXiv
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Main Authors: Jiao, Yifeng, Liu, Yuchen, Zhang, Yu, Guo, Xin, Wu, Yushuai, Jiang, Chen, Li, Jiyang, Zhang, Hongwei, Han, Limei, Gao, Xin, Qi, Yuan, Cheng, Yuan
Format: Preprint
Published: 2025
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author Jiao, Yifeng
Liu, Yuchen
Zhang, Yu
Guo, Xin
Wu, Yushuai
Jiang, Chen
Li, Jiyang
Zhang, Hongwei
Han, Limei
Gao, Xin
Qi, Yuan
Cheng, Yuan
author_facet Jiao, Yifeng
Liu, Yuchen
Zhang, Yu
Guo, Xin
Wu, Yushuai
Jiang, Chen
Li, Jiyang
Zhang, Hongwei
Han, Limei
Gao, Xin
Qi, Yuan
Cheng, Yuan
contents The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present ChromFound, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.
format Preprint
id arxiv_https___arxiv_org_abs_2505_12638
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle ChromFound: Towards A Universal Foundation Model for Single-Cell Chromatin Accessibility Data
Jiao, Yifeng
Liu, Yuchen
Zhang, Yu
Guo, Xin
Wu, Yushuai
Jiang, Chen
Li, Jiyang
Zhang, Hongwei
Han, Limei
Gao, Xin
Qi, Yuan
Cheng, Yuan
Genomics
Artificial Intelligence
Computational Engineering, Finance, and Science
Machine Learning
The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present ChromFound, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.
title ChromFound: Towards A Universal Foundation Model for Single-Cell Chromatin Accessibility Data
topic Genomics
Artificial Intelligence
Computational Engineering, Finance, and Science
Machine Learning
url https://arxiv.org/abs/2505.12638