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SPACE: a web server for linking chromatin accessibility with clinical phenotypes and the immune microenvironment in pan-cancer analysis

Cellular & Molecular Immunology volume 17, pages 1294–1296 (2020)Cite this article

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Noncoding “junk DNA”, which constitutes 98% of our genome, is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity. One feature of functional “junk DNA” is its accessibility. In cancer cells, aberrant chromatin accessibility is recognized as one of the major hallmarks. Understanding such events requires high-throughput screening, such as Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), which generates large-scale data that are puzzling for biologists. However, existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes. Here, we developed Shiny Pan-cancer Accessible Chromatin Explorer (SPACE) as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types. To the best of our knowledge, SPACE is the first web application supporting ATAC-seq analysis with matched clinical phenotype and transcriptome data. The current version of SPACE supports the following: (i) searching of ranked regulatory elements (peaks); (ii) exploration of potential regulators of peaks; (iii) examination of the clinical relevance of selected peaks; (iv) prediction of peak-related pathways; (v) correlations of peaks with RNAs; and (vi) exploration of the role of peaks in the immune-related tumor microenvironment. Thus, SPACE is an operable and time-saving epigenetic resource for cancer biologists to examine the transcriptional and phenotypic consequences of DNA regulatory elements. SPACE is available at http://fun-science.club/SPACE.

In cancer cells, dynamic DNA accessibility orchestrates a precise regulatory network to foster oncogenes in cancer. State-of-the-art high-throughput technologies, such as ATAC-seq, can provide a precise map for understanding how chromatin states manipulate oncogenesis, which places ATAC-seq right in the limelight of the epigenetics community.1 However, existing online tools, such as Cistrome2 or ENCODE,3 are useful for cell-line-based analysis but do little in clinical sample-based analysis. Thus, there is a pressing need for developing a user-friendly resource of regulatory elements with high-quality phenotypes or matched transcriptomes. Most recently, newly published ATAC-seq datasets of TCGA samples make it possible to explore the clinical value of chromatin accessibility.1 However, large-scale data generated by ATAC-seq are hard for biologists to directly analyze. Linking the epigenome to matched transcriptional and clinical information requires programming skills and IT infrastructure.

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References

  1. Corces, M. R. et al. The chromatin accessibility landscape of primary human cancers. Science 362, https://doi.org/10.1126/science.aav1898 (2018).

  2. Zheng, R. et al. Cistrome data browser: expanded datasets and new tools for gene regulatory analysis. Nucleic Acids Res. 47, D729–D735 (2019).

    Article  CAS  Google Scholar 

  3. Davis, C. A. et al. The encyclopedia of DNA elements (ENCODE): data portal update. Nucleic Acids Res. 46, D794–D801 (2018).

    Article  CAS  Google Scholar 

  4. Havel, J. J., Chowell, D. & Chan, T. A. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat. Rev. Cancer 19, 133–150 (2019).

    Article  CAS  Google Scholar 

  5. Xu, Y. et al. A tumor-specific super-enhancer drives immune evasion by guiding synchronous expression of PD-L1 and PD-L2. Cell Rep. 29, 3435–3447.e4 (2019).

    Article  CAS  Google Scholar 

  6. Zhang, X. et al. Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nat. Genet. 48, 176–182 (2016).

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (31770935; 81873531; 31970616); the Distinguished Professorship Program of Jiangsu Province to YF; the Distinguished Professorship Program of Jiangsu Province to RM; the National Undergraduate Training Programs for Innovation (201710304030Z); and the National Undergraduate Training Programs for Innovation (201810304026Z).

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Authors and Affiliations

  1. Department of Pathogenic Biology, School of Medicine, Nantong University, Jiangsu, 226001, China

    Yingcheng Wu, Jingwei Zhao, Haoliang Zhu, Zhiwei Fan, Xinpei Yuan, Shiyin Chen & Yihui Fan

  2. Laboratory of Medical Science, School of Medicine, Nantong University, Jiangsu, 226001, China

    Yingcheng Wu, Zhiwei Fan & Yihui Fan

  3. Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, 226001, China

    Jingwei Zhao, Haoliang Zhu, Xinpei Yuan, Shiyin Chen & Renfang Mao

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  1. Yingcheng Wu
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  2. Jingwei Zhao
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Correspondence to Renfang Mao or Yihui Fan.

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Wu, Y., Zhao, J., Zhu, H. et al. SPACE: a web server for linking chromatin accessibility with clinical phenotypes and the immune microenvironment in pan-cancer analysis. Cell Mol Immunol 17, 1294–1296 (2020). https://doi.org/10.1038/s41423-020-0416-9

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