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Application of high-throughput, high-depth, targeted single-nucleus DNA sequencing in pancreatic cancer

Zhang H et al.
BioRxiv (2022)

Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve the admixture of normal and tumor cells, and/or of distinct tumor subclones; high throughput single-cell DNA sequencing circumvents these and brings cancer genomic studies to higher resolution. However, its application has been limited to liquid tumors or a small batch of solid tumors, mainly because of the lack of a scalable workflow to process solid tumor samples. Here we optimized a highly automated nuclei extraction workflow that achieved fast and reliable targeted single-nucleus DNA library preparation of 38 samples from 16 pancreatic adenocarcinoma (PDAC) patients, with an average library yield per sample of 2867 single nuclei. We demonstrate that this workflow not only performs well using low cellularity or low tumor purity samples but reveals novel genomic evolution patterns of PDAC as well.


Zhang H, Karnoub E, Umeda S, Chaligné R, Masilionis I, McIntyre C, Hayashi A, Sashittal P, Zucker A, Mullen K, Makohon-Moore A, Iacobuzio-Donahue C


Phenotypic signatures of immune selection in HIV-1 reservoir cells
Weiwei Sun
Mutated cells mediate distinct inflammatory responses in clonal hematopoiesis
J. Brett Heimlich
scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells
Bianchi A
Genome Biology (2022)
Single cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia
Troy T. Robinson
BioRxiv (2022)