PT  - JOURNAL ARTICLE
AU  - Haochen Zhang
AU  - Elias-Ramzey Karnoub
AU  - Shigeaki Umeda
AU  - Ronan Chaligné
AU  - Ignas Masilionis
AU  - Caitlin A. McIntyre
AU  - Akimasa Hayashi
AU  - Palash Sashittal
AU  - Amanda Zucker
AU  - Katelyn Mullen
AU  - Alvin Makohon-Moore
AU  - Christine A. Iacobuzio-Donahue
TI  - Application of high-throughput, high-depth, targeted single-nucleus DNA sequencing in pancreatic cancer
AID  - 10.1101/2022.03.06.483206
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.06.483206
4099  - http://biorxiv.org/content/early/2022/03/07/2022.03.06.483206.short
4100  - http://biorxiv.org/content/early/2022/03/07/2022.03.06.483206.full
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.