Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)

Abstract Chip scale DNA synthesis offers a high-throughput and cost-effective method for large-scale DNA-based information storage. Nevertheless, unbiased information retrieval from low-copy-number sequences remains a barricade that largely arises from the indispensable DNA amplification. Here, we d...

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Main Authors: Zhi Weng, Jiangxue Li, Yi Wu, Xuehao Xiu, Fei Wang, Xiaolei Zuo, Ping Song, Chunhai Fan
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-55986-9
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author Zhi Weng
Jiangxue Li
Yi Wu
Xuehao Xiu
Fei Wang
Xiaolei Zuo
Ping Song
Chunhai Fan
author_facet Zhi Weng
Jiangxue Li
Yi Wu
Xuehao Xiu
Fei Wang
Xiaolei Zuo
Ping Song
Chunhai Fan
author_sort Zhi Weng
collection DOAJ
description Abstract Chip scale DNA synthesis offers a high-throughput and cost-effective method for large-scale DNA-based information storage. Nevertheless, unbiased information retrieval from low-copy-number sequences remains a barricade that largely arises from the indispensable DNA amplification. Here, we devise a simulation-guided quantitative primer-template hybridization strategy to realize massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS). Using a fixed-energy primer design, we demonstrate the unbiasedness of MPHAC for amplifying 100,000-plex sequences. Simulations reveal that MPHAC achieves a fold-80 value of 1.0 compared to 3.2 with conventional fixed-length primers, lowering costs by up to four orders of magnitude through reduced over-sequencing. The MPHAC-DIS system using 35,406 encoded oligonucleotide allows simultaneous access of multimedia files including text, images, and videos with high decoding accuracy at very low sequencing depths. Specifically, even a ~ 1 ×  sequencing depth, with the combination of machine learning, results in an acceptable decoding accuracy of ~80%. The programmable and predictable MPHAC-DIS method thus opens new door for DNA-based large-scale data storage with potential industrial applications.
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issn 2041-1723
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publisher Nature Portfolio
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spelling doaj-art-876ced0de6e0401db984ff7e39e056f32025-01-19T12:29:54ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-025-55986-9Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)Zhi Weng0Jiangxue Li1Yi Wu2Xuehao Xiu3Fei Wang4Xiaolei Zuo5Ping Song6Chunhai Fan7School of Biomedical Engineering, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong UniversitySchool of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong UniversityAbstract Chip scale DNA synthesis offers a high-throughput and cost-effective method for large-scale DNA-based information storage. Nevertheless, unbiased information retrieval from low-copy-number sequences remains a barricade that largely arises from the indispensable DNA amplification. Here, we devise a simulation-guided quantitative primer-template hybridization strategy to realize massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS). Using a fixed-energy primer design, we demonstrate the unbiasedness of MPHAC for amplifying 100,000-plex sequences. Simulations reveal that MPHAC achieves a fold-80 value of 1.0 compared to 3.2 with conventional fixed-length primers, lowering costs by up to four orders of magnitude through reduced over-sequencing. The MPHAC-DIS system using 35,406 encoded oligonucleotide allows simultaneous access of multimedia files including text, images, and videos with high decoding accuracy at very low sequencing depths. Specifically, even a ~ 1 ×  sequencing depth, with the combination of machine learning, results in an acceptable decoding accuracy of ~80%. The programmable and predictable MPHAC-DIS method thus opens new door for DNA-based large-scale data storage with potential industrial applications.https://doi.org/10.1038/s41467-025-55986-9
spellingShingle Zhi Weng
Jiangxue Li
Yi Wu
Xuehao Xiu
Fei Wang
Xiaolei Zuo
Ping Song
Chunhai Fan
Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
Nature Communications
title Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
title_full Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
title_fullStr Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
title_full_unstemmed Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
title_short Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
title_sort massively parallel homogeneous amplification of chip scale dna for dna information storage mphac dis
url https://doi.org/10.1038/s41467-025-55986-9
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