Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget

Abstract Camera-based single-molecule techniques have emerged as crucial tools in revolutionizing the understanding of biochemical and cellular processes due to their ability to capture dynamic processes with high precision, high-throughput capabilities, and methodological maturity. However, the str...

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Main Authors: Yu Miao, Yuxiao Cheng, Yushi Xia, Yongzhen Hei, Wenjuan Wang, Qionghai Dai, Jinli Suo, Chunlai Chen
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54652-w
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author Yu Miao
Yuxiao Cheng
Yushi Xia
Yongzhen Hei
Wenjuan Wang
Qionghai Dai
Jinli Suo
Chunlai Chen
author_facet Yu Miao
Yuxiao Cheng
Yushi Xia
Yongzhen Hei
Wenjuan Wang
Qionghai Dai
Jinli Suo
Chunlai Chen
author_sort Yu Miao
collection DOAJ
description Abstract Camera-based single-molecule techniques have emerged as crucial tools in revolutionizing the understanding of biochemical and cellular processes due to their ability to capture dynamic processes with high precision, high-throughput capabilities, and methodological maturity. However, the stringent requirement in photon number per frame and the limited number of photons emitted by each fluorophore before photobleaching pose a challenge to achieving both high temporal resolution and long observation times. In this work, we introduce MUFFLE, a supervised deep-learning denoising method that enables single-molecule FRET with up to 10-fold reduction in photon requirement per frame. In practice, MUFFLE extends the total number of observation frames by a factor of 10 or more, greatly relieving the trade-off between temporal resolution and observation length and allowing for long-term measurements even without the need for oxygen scavenging systems and triplet state quenchers.
format Article
id doaj-art-33fa399fda404137aacac07228585522
institution Kabale University
issn 2041-1723
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-33fa399fda404137aacac072285855222025-01-05T12:38:41ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-024-54652-wSupervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budgetYu Miao0Yuxiao Cheng1Yushi Xia2Yongzhen Hei3Wenjuan Wang4Qionghai Dai5Jinli Suo6Chunlai Chen7State Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityDepartment of Automation, Tsinghua UniversityState Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityState Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityTechnology Center for Protein Sciences, School of Life Sciences, Tsinghua UniversityDepartment of Automation, Tsinghua UniversityDepartment of Automation, Tsinghua UniversityState Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityAbstract Camera-based single-molecule techniques have emerged as crucial tools in revolutionizing the understanding of biochemical and cellular processes due to their ability to capture dynamic processes with high precision, high-throughput capabilities, and methodological maturity. However, the stringent requirement in photon number per frame and the limited number of photons emitted by each fluorophore before photobleaching pose a challenge to achieving both high temporal resolution and long observation times. In this work, we introduce MUFFLE, a supervised deep-learning denoising method that enables single-molecule FRET with up to 10-fold reduction in photon requirement per frame. In practice, MUFFLE extends the total number of observation frames by a factor of 10 or more, greatly relieving the trade-off between temporal resolution and observation length and allowing for long-term measurements even without the need for oxygen scavenging systems and triplet state quenchers.https://doi.org/10.1038/s41467-024-54652-w
spellingShingle Yu Miao
Yuxiao Cheng
Yushi Xia
Yongzhen Hei
Wenjuan Wang
Qionghai Dai
Jinli Suo
Chunlai Chen
Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget
Nature Communications
title Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget
title_full Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget
title_fullStr Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget
title_full_unstemmed Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget
title_short Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget
title_sort supervised multi frame dual channel denoising enables long term single molecule fret under extremely low photon budget
url https://doi.org/10.1038/s41467-024-54652-w
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