Abstract

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-μm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

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Sequence Read Archive

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Gene Expression Omnibus

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Acknowledgements

We thank the Stanford Alzheimer's Disease Research Center (NIH P50 AG047366; to V. Henderson), the Pacific Udall Center for Excellence in Parkinson's Disease Research (NIH P50 NS062684; T.J.M.), and their participants for donating samples for research. We also thank J. Coller and X. Ji for sequencing assistance, E. Plowey and D. Channappa for tissue preparation, and P. Chu and A. Grewall for histology assistance. This work was supported by a grant from the Leukemia & Lymphoma Society Career Development Program (M.R.C.), US National Institutes of Health (NIH) training grant R25CA180993 (M.R.C.), NIH grants P50-HG007735 (H.Y.C. and W.J.G.), UM1HG00943 (W.J.G.), and U19AI057266 (W.J.G.), National Institute on aging grant RF1 AG053959 (T.J.M.), the Rita Allen Foundation (W.J.G.), the Human Frontier Science Program (W.J.G.), the National Science Foundation Graduate Research Fellowship Program (A.E.T.), and a US Department of Defense National Defense Science and Engineering Graduate (NDSEG) Fellowship (N.A.S.-A.).

Author information

Affiliations

  1. Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.

    • M Ryan Corces
    • , Alexandro E Trevino
    • , Ansuman T Satpathy
    • , Seung Woo Cho
    • , Maxwell R Mumbach
    • , Ava C Carter
    • , Maya Kasowski
    • , William J Greenleaf
    •  & Howard Y Chang
  2. Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.

    • M Ryan Corces
    • , Adam J Rubin
    • , Seung Woo Cho
    • , Ava C Carter
    • , Paul A Khavari
    •  & Howard Y Chang
  3. Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

    • Alexandro E Trevino
    • , Peyton G Greenside
    • , Nicholas A Sinnott-Armstrong
    • , Beijing Wu
    • , Arwa Kathiria
    • , Maxwell R Mumbach
    • , Viviana I Risca
    • , Anshul Kundaje
    •  & William J Greenleaf
  4. Department of Bioengineering, Stanford University School of Medicine and School of Engineering, Stanford, California, USA.

    • Alexandro E Trevino
    •  & Sam Vesuna
  5. Program in Cancer Biology, Stanford University School of Medicine, Stanford, California, USA.

    • Emily G Hamilton
  6. Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, California, USA.

    • Peyton G Greenside
  7. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

    • Ansuman T Satpathy
    • , Kathleen S Montine
    • , Maya Kasowski
    •  & Thomas J Montine
  8. Department of Otolaryngology Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA.

    • Lisa A Orloff
  9. Department of Computer Science, Stanford University, Stanford, California, USA.

    • Anshul Kundaje
  10. Chan Zuckerberg Biohub, San Francisco, California, USA.

    • William J Greenleaf

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Contributions

M.R.C. and H.Y.C. conceived the project; M.R.C., E.G.H., and A.T.S. performed all of the experiments, with help from M.R.M. and A.C.C.; S.W.C. produced the Tn5 transposase complex that was used in all of the experiments; P.G.G. performed all of the GWAS analysis, with guidance and supervision from A. Kundaje; M.R.C. and A.J.R. performed all other data analysis; M.R.C., A.E.T., S.V., and N.A.S.-A., developed methods for the isolation of nuclei from frozen tissues; B.W., A. Kathiria, V.I.R., and W.J.G. provided protocol expertise and recommendations; K.S.M. and T.J.M. oversaw all brain tissue acquisition and processing; M.K. and L.A.O. oversaw acquisition and processing of thyroid cancer tissue; A.J.R. and P.A.K. oversaw acquisition and processing of primary foreskin keratinocytes; and M.R.C., E.G.H., W.J.G., and H.Y.C. wrote the manuscript with input from all authors.

Competing interests

H.Y.C. and W.J.G. are co-founders and consultants of Epinomics. A. Kundaje is a member of the scientific advisory board of Epinomics.

Corresponding authors

Correspondence to William J Greenleaf or Howard Y Chang.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–9 and Supplementary Note 1.

  2. 2.

    Life Sciences Reporting Summary

    Life Sciences Reporting Summary.

  3. 3.

    Supplementary Protocol 1

    Omni-ATAC: Improved ATAC-seq protocol.

  4. 4.

    Supplementary Protocol 2

    Isolation of nuclei from frozen tissues.

Excel files

  1. 1.

    Supplementary Table 1

    Sequencing statistics for all libraries generated in this work.

  2. 2.

    Supplementary Table 2

    Clinical characteristics of brain donors.

  3. 3.

    Supplementary Table 3

    Empirical p values and enrichment values for all GWAS data.

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DOI

https://doi.org/10.1038/nmeth.4396

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