Barcoded multiple displacement amplification for high coverage sequencing in spatial genomics

Author:

Kim JinhyunORCID,Kim Sungsik,Yeom HuiranORCID,Song Seo WooORCID,Shin Kyoungseob,Bae Sangwook,Ryu Han SukORCID,Kim Ji Young,Choi Ahyoun,Lee Sumin,Ryu TaehoonORCID,Choi Yeongjae,Kim Hamin,Kim Okju,Jung Yushin,Kim Namphil,Han WonshikORCID,Lee Han-ByoelORCID,Lee Amos C.ORCID,Kwon SunghoonORCID

Abstract

AbstractDetermining 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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