DNA测序
计算生物学
生物
亚细胞定位
DNA微阵列
DNA
细胞生物学
分子生物学
基因
基因表达
遗传学
作者
Noah R. Sundah,Nicholas R. Y. Ho,Geok Soon Lim,Auginia Natalia,Xiaoyun Ding,Yu Liu,Ju Ee Seet,Ching Wan Chan,Tze Ping Loh,Huilin Shao
标识
DOI:10.1038/s41551-019-0417-0
摘要
Massively parallel DNA sequencing is established, yet high-throughput protein profiling remains challenging. Here, we report a barcoding approach that leverages the combinatorial sequence content and the configurational programmability of DNA nanostructures for high-throughput multiplexed profiling of the subcellular expression and distribution of proteins in whole cells. The barcodes are formed by in situ hybridization of tetrahedral DNA nanostructures and short DNA sequences conjugated with protein-targeting antibodies, and by nanostructure-assisted ligation (either enzymatic or chemical) of the nanostructures and exogenous DNA sequences bound to nanoparticles of different sizes (which cause these localization sequences to differentially distribute across subcellular compartments). Compared with linear DNA barcoding, the nanostructured barcodes enhance the signal by more than 100-fold. By implementing the barcoding approach on a microfluidic device for the analysis of rare patient samples, we show that molecular subtypes of breast cancer can be accurately classified and that subcellular spatial markers of disease aggressiveness can be identified.
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