Jinhyun Kim, Sungsik Kim, Huiran Yeom, Seo Woo Song, Kyoungseob Shin, Sangwook Bae, Han Suk Ryu, Ji Young Kim, Ahyoun Choi, Sumin Lee, Taehoon Ryu, Yeongjae Choi, Hamin Kim, Okju Kim, Yushin Jung, Namphil Kim, Wonshik Han, Han-Byoel Lee, Amos C. Lee, & Sunghoon Kwon
Nature Communications


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.