Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity
Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility...
Main Authors: | , , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Nature Research
2022
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Subjects: | |
Online Access: | View Fulltext in Publisher |
LEADER | 02418nam a2200409Ia 4500 | ||
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001 | 10.1038-s41467-022-29857-6 | ||
008 | 220510s2022 CNT 000 0 und d | ||
020 | |a 20411723 (ISSN) | ||
245 | 1 | 0 | |a Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity |
260 | 0 | |b Nature Research |c 2022 | |
856 | |z View Fulltext in Publisher |u https://doi.org/10.1038/s41467-022-29857-6 | ||
520 | 3 | |a Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications. © 2022, The Author(s). | |
650 | 0 | 4 | |a cancer |
650 | 0 | 4 | |a cell component |
650 | 0 | 4 | |a drug |
650 | 0 | 4 | |a integrated approach |
700 | 1 | |a Chen, L. |e author | |
700 | 1 | |a Gao, D. |e author | |
700 | 1 | |a Gao, S. |e author | |
700 | 1 | |a Guo, S. |e author | |
700 | 1 | |a Han, M. |e author | |
700 | 1 | |a He, J. |e author | |
700 | 1 | |a Jin, G. |e author | |
700 | 1 | |a Jing, W. |e author | |
700 | 1 | |a Li, Y. |e author | |
700 | 1 | |a Liu, Z. |e author | |
700 | 1 | |a Shi, X. |e author | |
700 | 1 | |a Tang, S. |e author | |
700 | 1 | |a Wang, H. |e author | |
700 | 1 | |a Wang, Y. |e author | |
700 | 1 | |a Xu, X. |e author | |
700 | 1 | |a Yuan, Q. |e author | |
700 | 1 | |a Zhang, X. |e author | |
700 | 1 | |a Zhang, Y. |e author | |
700 | 1 | |a Zheng, K. |e author | |
700 | 1 | |a Zhu, Y. |e author | |
773 | |t Nature Communications |