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细胞记忆:使用瓶颈变压器对分布外细胞进行分层解释。

CellMemory: hierarchical interpretation of out-of-distribution cells using bottlenecked transformer.

作者信息

Wang Qifei, Zhu He, Hu Yiwen, Chen Yanjie, Wang Yuwei, Li Guochao, Li Yun, Chen Jinfeng, Zhang Xuegong, Zou James, Kellis Manolis, Li Yue, Liu Dianbo, Jiang Lan

机构信息

China National Center for Bioinformation, Beijing, 100101, China.

Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Genome Biol. 2025 Jun 23;26(1):178. doi: 10.1186/s13059-025-03638-y.


DOI:10.1186/s13059-025-03638-y
PMID:40551223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12183866/
Abstract

Machine learning methods, especially Transformer architectures, have been widely employed in single-cell omics studies. However, interpretability and accurate representation of out-of-distribution (OOD) cells remains challenging. Inspired by the global workspace theory in cognitive neuroscience, we introduce CellMemory, a bottlenecked Transformer with improved generalizability designed for the hierarchical interpretation of OOD cells. Without pre-training, CellMemory outperforms existing single-cell foundation models and accurately deciphers spatial transcriptomics at high resolution. Leveraging its robust representations, we further elucidate malignant cells and their founder cells across patients, providing reliable characterizations of the cellular changes caused by the disease.

摘要

机器学习方法,尤其是Transformer架构,已在单细胞组学研究中得到广泛应用。然而,对分布外(OOD)细胞的可解释性和准确表征仍然具有挑战性。受认知神经科学中全局工作空间理论的启发,我们引入了CellMemory,这是一种具有改进泛化能力的瓶颈Transformer,专为OOD细胞的分层解释而设计。无需预训练,CellMemory优于现有的单细胞基础模型,并能在高分辨率下准确解码空间转录组学。利用其强大的表征能力,我们进一步阐明了不同患者的恶性细胞及其起源细胞,为该疾病引起的细胞变化提供了可靠的特征描述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/51c475355660/13059_2025_3638_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/8b83bc97bab6/13059_2025_3638_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/35007188263e/13059_2025_3638_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/b194d038dbc3/13059_2025_3638_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/56804d545d7b/13059_2025_3638_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/fed06bff7635/13059_2025_3638_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/51c475355660/13059_2025_3638_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/8b83bc97bab6/13059_2025_3638_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/35007188263e/13059_2025_3638_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/b194d038dbc3/13059_2025_3638_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/56804d545d7b/13059_2025_3638_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/fed06bff7635/13059_2025_3638_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d3/12183866/51c475355660/13059_2025_3638_Fig6_HTML.jpg

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本文引用的文献

[1]
Transformers in single-cell omics: a review and new perspectives.

Nat Methods. 2024-8

[2]
Harnessing the deep learning power of foundation models in single-cell omics.

Nat Rev Mol Cell Biol. 2024-8

[3]
The future of rapid and automated single-cell data analysis using reference mapping.

Cell. 2024-5-9

[4]
Tracing the origin of alveolar stem cells in lung repair and regeneration.

Cell. 2024-5-9

[5]
Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Cell Rep Med. 2024-4-16

[6]
scGPT: toward building a foundation model for single-cell multi-omics using generative AI.

Nat Methods. 2024-8

[7]
EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation.

J Exp Med. 2024-3-4

[8]
High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis.

Nat Commun. 2023-12-19

[9]
Slide-tags enables single-nucleus barcoding for multimodal spatial genomics.

Nature. 2024-1

[10]
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.

Nature. 2023-12

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