권성훈 (서울대학교, 바이오맥스)

한빛사논문

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서울대학교, 바이오맥스

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Nat. Commun., 2023 Aug 29;14(1):5261 | https://doi.org/10.1038/s41467-023-41019-w Barcoded multiple displacement amplification for high coverage sequencing in spatial genomics

Jinhyun Kim ¹, Sungsik Kim ², Huiran Yeom ³, Seo Woo Song ⁴, Kyoungseob Shin¹, Sangwook Bae ⁵, Han Suk Ryu ^6,7, Ji Young Kim ⁸, Ahyoun Choi ², Sumin Lee ^1,15, Taehoon Ryu ⁹, Yeongjae Choi ¹⁰, Hamin Kim ², Okju Kim ⁹, Yushin Jung ⁹, Namphil Kim ¹, Wonshik Han ^6,8,11, Han-Byoel Lee ^6,8,11,*, Amos C. Lee ^12,15,* & Sunghoon Kwon ^{1,2,8,12,13,14,*}

¹Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of Korea.
²Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.
³Division of Data Science, College of Information and Communication Technology, The University of Suwon, Hwaseong 18323, Republic of Korea.
⁴Basic Science and Engineering Initiative, Children’s Heart Center, Stanford University, Stanford, CA, USA.
⁵Renal Division and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
⁶Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
⁷Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
⁸Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
⁹ATG Lifetech Inc., Seoul 08507, Republic of Korea.
¹⁰School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
¹¹Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
¹²Bio-MAX Institute, Seoul National University, Seoul 08826, Republic of Korea.
¹³Inter-University Semiconductor Research Center, Seoul National University, Seoul 08826, Republic of Korea.
¹⁴Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul 08826, Republic of Korea.
¹⁵Present address: Meteor Biotech, Co. Ltd., Seoul 08826, Republic of Korea.

^*Corresponding author: correspondence to Han-Byoel Lee, Amos C. Lee or Sunghoon Kwon

Abstract

Determining mutational landscapes in a spatial context is essential for understanding genetically heterogeneous cell microniches. Current approaches, such as Multiple Displacement Amplification (MDA), offer high genome coverage but limited multiplexing, which hinders large-scale spatial genomic studies. Here, we introduce barcoded MDA (bMDA), a technique that achieves high-coverage genomic analysis of low-input DNA while enhancing the multiplexing capabilities. By incorporating cell barcodes during MDA, bMDA streamlines library preparation in one pot, thereby overcoming a key bottleneck in spatial genomics. We apply bMDA to the integrative spatial analysis of triple-negative breast cancer tissues by examining copy number alterations, single nucleotide variations, structural variations, and kataegis signatures for each spatial microniche. This enables the assessment of subclonal evolutionary relationships within a spatial context. Therefore, bMDA has emerged as a scalable technology with the potential to advance the field of spatial genomics significantly.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-09-05)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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