An integrative ENCODE resource for cancer genomics
Open accessPublished version of a preprint
Abstract
ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNA-binding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a well-known oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource.
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STAT3 activation potentiates IL-6 signaling by increasing receptor and ligand levels.
“STAT3 activation potentiates IL-6 signaling by increasing receptor and ligand levels”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [35]
The Results section on regulatory networks discusses MYC and SUB1 regulation, not STAT3 activation or IL-6 signaling. Searches for STAT3, IL-6, and receptor and ligand levels found no passage in our copy addressing the claimed mechanism. (LLM, conf=0.76)
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The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11
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Suita, Y., Bright, H., Pu, Y., Toruner, M. D., Idehen, J., Tapinos, N., & Singh, R. (2025) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012272 · Cited by 5 · see citing works
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Self-citationHomeotic and nonhomeotic patterns in the tetrapod vertebral formula
Cerbus, R., Hiratani, I., & Kawaguchi, K. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2411421121 · Cited by 5 · see citing works
Elongin functions as a loading factor for Mediator at ATF6α-regulated ER stress response genes
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- Authors
- Zhang, J., Lee, D., Dhiman, V., Jiang, P., Xu, J., McGillivray, P., Yang, H., Liu, J., Meyerson, W., Clarke, D., Gu, M., Li, S., Lou, S., Xu, J., Lochovsky, L., Ung, M., Ma, L., Yu, S., Cao, Q., Harmanci, A., Yan, K.-K., Sethi, A., Gürsoy, G., Schoenberg, M. R., Rozowsky, J., Warrell, J., Emani, P., Yang, Y. T., Galeev, T., Kong, X., Liu, S., Li, X., Krishnan, J., Feng, Y., Rivera-Mulia, J. C., Adrian, J., Broach, J. R., Bolt, M., Moran, J., Fitzgerald, D., Dileep, V., Liu, T., Mei, S., Sasaki, T., Trevilla-Garcia, C., Wang, S., Wang, Y., Zang, C., Wang, D., Klein, R. J., Snyder, M., Gilbert, D. M., Yip, K., Cheng, C., Yue, F., Liu, X. S., White, K. P., & Gerstein, M.
- Affiliations
- Yale University (US)
- University of Chicago (US)
- National Institutes of Health (US)
- Northwestern University (US)
- Dartmouth College (US)
- Westlake University (CN)
- Chinese University of Hong Kong (HK)
- The University of Texas Health Science Center at Houston (US)
- Pennsylvania State University (US)
- Florida State University (US)
- Harvard University (US)
- University of Virginia (US)
- University of Wisconsin–Madison (US)
- Icahn School of Medicine at Mount Sinai (US)
- Stanford University (US)
- Corresponding author
- Yue, Feng
- Liu, X. Shirley
- White, Kevin P.
- Gerstein, Mark
- ORCID
- Zhang, Jing
- Lee, Donghoon
- Dhiman, Vineet
- Jiang, Peng
- Xu, Jie
- McGillivray, Patrick
- Yang, Hongbo
- Liu, Jason
- Meyerson, William
- Clarke, Declan
- Gu, Mengting
- Li, Shantao
- Lou, Shaoke
- Xu, Jinrui
- Lochovsky, Lucas
- Ung, Matthew
- Yu, Shan
- Cao, Qin
- Harmanci, Arif
- Sethi, Anurag
- Gürsoy, Gamze
- Rozowsky, Joel
- Warrell, Jonathan
- Emani, Prashant
- Yang, Yucheng T.
- Galeev, Timur
- Liu, Shuang
- Li, Xiaotong
- Feng, Yanlin
- Rivera-Mulia, Juan Carlos
- Adrian, Jessica
- Broach, James R
- Moran, Jennifer
- Fitzgerald, Dominic
- Dileep, Vishnu
- Liu, Tingting
- Mei, Shenglin
- Sasaki, Takayo
- Wang, Su
- Wang, Yanli
- Zang, Chongzhi
- Wang, Daifeng
- Klein, Robert J.
- Snyder, Michael
- Gilbert, David M.
- Yip, Kevin
- Cheng, Chao
- Yue, Feng
- Liu, X. Shirley
- White, Kevin P.
- Gerstein, Mark
- Venue
- Nature Communications
- Published
- 2020-07-29
- Volume
- 11
- Issue
- 1
- Pages
- 3696-3696
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7391744
- OpenAlex
- W3045759143
- Cited by
- 172
- References
- 80
- Citations by year
- 2026: 23 · 2025: 37 · 2024: 26 · 2023: 24 · 2022: 28 · 2021: 27 · 2020: 5 · 2019: 1 · 2018: 1
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (U24HG009446)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- ENCODE, cancer genomics, transcriptional regulatory networks, RNA-binding proteins, network rewiring, carcinogenesis, c-Myc, SUB1, variant prioritization, genome-wide association study, eCLIP, Hi-C, STARR-seq
- MeSH terms
- Cell Transformation, Neoplastic, Humans, Mutation, Neoplasms, Transcription Factors, Reproducibility of Results, Genomics, Databases, Genetic, Cell Line, Tumor, Gene Regulatory Networks
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