RT Journal Article
SR Electronic
T1 Application of high-throughput, high-depth, targeted single-nucleus DNA sequencing in pancreatic cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.06.483206
DO 10.1101/2022.03.06.483206
A1 Haochen Zhang
A1 Elias-Ramzey Karnoub
A1 Shigeaki Umeda
A1 Ronan Chaligné
A1 Ignas Masilionis
A1 Caitlin A. McIntyre
A1 Akimasa Hayashi
A1 Palash Sashittal
A1 Amanda Zucker
A1 Katelyn Mullen
A1 Alvin Makohon-Moore
A1 Christine A. Iacobuzio-Donahue
YR 2022
UL http://biorxiv.org/content/early/2022/03/07/2022.03.06.483206.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.