Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29857-6
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Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16020905, XDB38040400]
- National key research and development program of China [2017YFA0505500, 2020YFA0509000, 2020YFA0712402]
- Basic Frontier Science Research Program of Chinese Academy of Sciences [ZDBS-LY-SM015]
- National Natural Science Foundation of China [32125013, 81830054, 81772723, 31930022, 31771476, 12131020, 12026608, 82002559, 82172589, 81972913, 82172712, 12025107, 11871463, 61621003]
- Shanghai Science and Technology Committee [21XD1424200, 21ZR1470100, 20ZR1456500, 20511101200]
- JST Moonshot RD [JPMJMS2021]
- Shanghai ShenKang hospital development center [SHDC2020CR2001A]
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This study reveals the gene regulatory networks and molecular subtypes of pancreatic cancer through multi-omics analysis of 84 organoid lines.
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. The chromatin accessibility landscape and gene regulatory network of pancreatic cancer has not been fully characterised. Here, the authors perform multi-omics analysis of 84 pancreatic cancer organoid lines and reveal gene regulatory networks and distinct molecular subtypes.
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