Abstract
Learning cell identity from high-content single-cell data presently relies on human experts. We present marker enrichment modeling (MEM), an algorithm that objectively describes cells by quantifying contextual feature enrichment and reporting a human- and machine-readable text label. MEM outperforms traditional metrics in describing immune and cancer cell subsets from fluorescence and mass cytometry. MEM provides a quantitative language to communicate characteristics of new and established cytotypes observed in complex tissues.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
10 February 2017
In the version of this article initially published online, Jonathan M Irish was misspelled as Jonathon M Irish. The error has been corrected in the print, PDF and HTML versions of this article as of 10 Feburary 2017.
References
Diggins, K.E., Ferrell, P.B. Jr. & Irish, J.M. Methods 82, 55–63 (2015).
Saeys, Y., Gassen, S.V. & Lambrecht, B.N. Nat. Rev. Immunol. 16, 449–462 (2016).
Patel, A.P. et al. Science 344, 1396–1401 (2014).
Becher, B. et al. Nat. Immunol. 15, 1181–1189 (2014).
Greenplate, A.R., Johnson, D.B., Ferrell, P.B. Jr. & Irish, J.M. Eur. J. Cancer 61, 77–84 (2016).
Irish, J.M. et al. Cell 118, 217–228 (2004).
Irish, J.M. et al. Proc. Natl. Acad. Sci. USA 107, 12747–12754 (2010).
Levine, J.H. et al. Cell 162, 184–197 (2015).
Greenplate, A.R. et al. Cancer Immunol. Res. 4, 474–480 (2016).
Gaudillière, B. et al. Sci. Transl. Med. 6, 255ra131 (2014).
Young, I.T. J. Histochem. Cytochem. 25, 935–941 (1977).
Kim, D., Donnenberg, V.S., Wilson, J.W. & Donnenberg, A.D. Cytometry A 89, 89–97 (2016).
Orlova, D.Y. et al. PLoS One 11, e0151859 (2016).
Leelatian, N., Diggins, K.E. & Irish, J.M. Methods Mol. Biol. 1346, 99–113 (2015).
Bendall, S.C. et al. Science 332, 687–696 (2011).
Leelatian, N. et al. Cytometry B Clin. Cytom. http://dx.doi.org/10.1002/cyto.b.21481 (2016).
el-AD, Amir et al. Nat. Biotechnol. 31, 545–552 (2013).
Qiu, P. et al. Nat. Biotechnol. 29, 886–891 (2011).
Irish, J.M. Nat. Immunol. 15, 1095–1097 (2014).
IUIS-WHO Nomenclature Subcommittee. Bull. World Health Organ. 62, 809–815 (1984).
Kotecha, N., Krutzik, P.O. & Irish, J.M. In Current Protocols in Cytom. 53, 10.17.1–10.17.24 (2010).
Hahne, F. et al. BMC Bioinformatics 10, 106 (2009).
Warnes, G.R. et al. gplots: Various R Programming Tools for Plotting Data. http://cran.r-project.org/package=gplots (2016).
Lo, K. BMC Bioinformatics 10, 145 (2009).
Mosmann, T.R. et al. Cytometry A 85, 422–433 (2014).
Bruggner, R.V., Bodenmiller, B., Dill, D.L., Tibshirani, R.J. & Nolan, G.P. Proc. Natl. Acad. Sci. USA 111, E2770–E2777 (2014).
Shekhar, K., Brodin, P., Davis, M.M. & Chakraborty, A.K. Proc. Natl. Acad. Sci. USA 111, 202–207 (2014).
Bendall, S.C. et al. Cell 157, 714–725 (2014).
Spitzer, M.H. et al. Science 349, 1259425 (2015).
Chattopadhyay, P.K., Gierahn, T.M., Roederer, M. & Love, J.C. Nat. Immunol. 15, 128–135 (2014).
Ferrell, N.B. Jr. et al. PLoS One 11, e0153207 (2016).
Nicholas, K.J. et al. Cytometry A 89, 271–280 (2016).
Polikowsky, H.G., Wogsland, C.E., Diggins, K.E., Huse, K. & Irish, J.M. J. Immunol. 195, 1364–1367 (2015).
Leelatian, N., Diggins, K.E. & Irish, J.M. in Methods Mol. Biol. 1346, 99–113 (2015).
Cox, C., Reeder, J.E., Robinson, R.D., Suppes, S.B. & Wheeless, L.L. Cytometry 9, 291–298 (1988).
Civin, C.I. et al. J. Immunol. 133, 157–165 (1984).
Doulatov, S., Notta, F., Laurenti, E. & Dick, J.E. Cell Stem Cell 10, 120–136 (2012).
Basit, A. et al. Am. J. Physiol. Lung Cell. Mol. Physiol. 291, L200–L207 (2006).
Furze, R.C. & Rankin, S.M. Immunology 125, 281–288 (2008).
Acknowledgements
This study was supported by R25 CA136440-04 (K.E.D.), F31 CA199993 (A.R.G.), R00 CA143231-03 (J.M.I.), the Vanderbilt-Ingram Cancer Center (VICC, P30 CA68485), VICC Ambassadors, a VICC Hematology Helping Hands award (J.M.I. and K.E.D.), and the Vanderbilt International Scholars Program (N.L.). Thanks to M. Roussel for helpful discussions of myeloid cell identity markers, to D. Doxie for helpful discussions of MEM analysis of tumor and immune cell subsets, and to L. Chambless and R. Ihrie for use of glioma tumor data generated by N.L.
Author information
Authors and Affiliations
Contributions
All authors designed experiments, discussed data visualization, contributed intellectually to the manuscript, and approved the final manuscript. J.M.I. and K.E.D. performed computational analyses, developed analytical tools and protocols, conceived and designed the study, and wrote the manuscript. A.R.G. contributed to Figures 2 and 3 and assisted with manuscript revisions. N.L. contributed to Figure 3 and manuscript revisions. C.E.W. contributed to R code implementation and manuscript revisions.
Corresponding author
Ethics declarations
Competing interests
J.M.I. is cofounder and board member and Cytobank Inc. and received research support from Incyte Corp.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–6, Supplementary Tables 1–5 and Supplementary Notes 1–5 (PDF 3915 kb)
Supplementary Data 1
Supplementary Note 2 Underlying Data (XLSX 28 kb)
Supplementary Data 2
Supplementary Note 5-Figure 1 Underlying Data (XLSX 18 kb)
Supplementary Data 3
Supplementary Note 5-Figure 2 Underlying Data (XLSX 13 kb)
Supplementary Software
R package for MEM implementation (ZIP 4346 kb)
Source data
Rights and permissions
About this article
Cite this article
Diggins, K., Greenplate, A., Leelatian, N. et al. Characterizing cell subsets using marker enrichment modeling. Nat Methods 14, 275–278 (2017). https://doi.org/10.1038/nmeth.4149
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmeth.4149
This article is cited by
-
Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes
Communications Biology (2024)
-
Graph Fourier transform for spatial omics representation and analyses of complex organs
Nature Communications (2024)
-
Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab
Annals of Hematology (2024)
-
Dysregulation of developmental and cell type-specific expression of glycoconjugates on hematopoietic cells: a new characteristic of myelodysplastic neoplasms (MDS)
Leukemia (2023)
-
Learning cell identity in immunology, neuroscience, and cancer
Seminars in Immunopathology (2023)