Pancreatic cancer prognosis is predicted by a novel ATAC-array technology for assessing chromatin accessibility

Dhara, S.; Chhangawala, S.; Chintalapudi, H.; Askan, G.; Aveson, V.; Massa, A. L.; Zhang, L.; Makohon-Moore, A. P.; Lecomte, N.; Melchor, J. P.; Bermeo, J.; Cardenas, A.; Sinha, S.; Glassman, D.; Nicolle, R.; Moffitt, R.; Yu, K.; Leppanen, S.; Laderman, S.; Curry, B.; Gui, J.; Balachandran, V.; Iacobuzio-Donahue, C. A.; Chandwani, R.; Leslie, C. S.; Leach, S. D.

doi:10.1101/2021.01.21.427604

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bioRxiv · 10.1101/2021.01.21.427604

Pancreatic cancer prognosis is predicted by a novel ATAC-array technology for assessing chromatin accessibility

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Abstract

We investigated tumor-cell-intrinsic chromatin accessibility patterns of pancreatic ductal adenocarcinoma (PDAC) by ATAC-seq on EpCAM+ PDAC malignant epithelial cells, sorted from 54 freshly resected human tumors, and discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identified two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further developed a novel chromatin accessibility microarray methodology termed "ATAC-Array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this novel methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validated ATAC-array technology in both the original ATAC-Seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a novel, lowcost, clinically feasible technology for assessing chromatin accessibility profiles.

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Dhara, S., Chhangawala, S., Chintalapudi, H., Askan, G., Aveson, V., Massa, A. L., Zhang, L., Makohon-Moore, A. P., Lecomte, N., Melchor, J. P., Bermeo, J., Cardenas, A., Sinha, S., Glassman, D., Nicolle, R., Moffitt, R., Yu, K., Leppanen, S., Laderman, S., Curry, B., Gui, J., Balachandran, V., Iacobuzio-Donahue, C. A., Chandwani, R., Leslie, C. S., Leach, S. D.. 2021-01-22. Pancreatic cancer prognosis is predicted by a novel ATAC-array technology for assessing chromatin accessibility. https://doi.org/10.1101/2021.01.21.427604

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