Article
- Diedenhofen, B. & Musch, J. cocor: a comprehensive solution for the statistical
comparison of correlations. PLoS One 10 , e0121945 (2015). - Chao, A. et al. Rarefaction and extrapolation with Hill numbers: a framework for sampling
and estimation in species diversity studies. Ecol. Monogr. 84 , 45–67 (2014). - Therneau, T. M. & Grambsch, P. M. Modeling Survival Data: Extending the Cox Model
(Springer, 2000). - McInnes, L. & Healy, J. UMAP: uniform manifold approximation and projection for
dimension reduction. Preprint at https://arXiv.org/abs/1802.03426 (2018). - Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat.
Biotechnol. 37 , 38–44 (2019). - Zeileis, A. et al. colorspace: a toolbox for manipulating and assessing colors and palettes.
Preprint at https://arXiv.org/abs/1903.06490 (2019). - Barter, R. L. & Yu, B. Superheat: an R package for creating beautiful and extendable
heatmaps for visualizing complex data. J. Comput. Graph. Stat. 27 , 910–922 (2018). - Morgan, M. T. & Davis, S. R. GenomicDataCommons: a bioconductor interface to the NCI
Genomic Data Commons. Preprint at https://www.bioRxiv.org/content/10.1101/117200v1
(2017). - Davis, S. & Meltzer, P. S. GEOquery: a bridge between the Gene Expression Omnibus
(GEO) and BioConductor. Bioinformatics 23 , 1846–1847 (2007). - Shimizu, Y., Meunier, L. & Hendershot, L. M. pERp1 is significantly up-regulated during
plasma cell differentiation and contributes to the oxidative folding of immunoglobulin.
Proc. Natl Acad. Sci. USA 106 , 17013–17018 (2009). - Andreani, V. et al. Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell
differentiation and β1-integrin function. Proc. Natl Acad. Sci. USA 115 , E9630–E9639
(2018). - Beham, A. W. et al. A TNF-regulated recombinatorial macrophage immune receptor
implicated in granuloma formation in tuberculosis. PLoS Pathog. 7 , e1002375 (2011). - Fuchs, T. et al. Expression of combinatorial immunoglobulins in macrophages in the
tumor microenvironment. PLoS One 13 , e0204108 (2018). - Thul, P. J. et al. A subcellular map of the human proteome. Science 356 , 820 (2017).
- Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for
interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102 , 15545–
15550 (2005). - Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27 ,
1739–1740 (2011).
53. Irizarry, R. A., Wang, C., Zhou, Y. & Speed, T. P. Gene set enrichment analysis made simple.
Stat. Methods Med. Res. 18 , 565–575 (2009).
54. Shugay, M. et al. VDJdb: a curated database of T-cell receptor sequences with known
antigen specificity. Nucleic Acids Res. 46 , D419–D427 (2018).
55. Li, B. et al. Landscape of tumor-infiltrating T cell repertoire of human cancers. Nat. Genet.
48 , 725–732 (2016).
56. Shan, G. & Gerstenberger, S. Fisher’s exact approach for post hoc analysis of a chi-
squared test. PLoS One 12 , e0188709 (2017).
Acknowledgements We thank the Genentech FACS Core for supporting the prompt sorting of
T cells, and S. Kummerfeld for advice and assistance with initial data analyses. We also thank
A. Lun for discussions regarding reference gene signatures and labelling of single cells.Author contributions J.L.G. and P.E.dA. conceived and designed the study. T.D.W.
conceived and performed bioinformatic data analysis and generated figures. P.E.dA.,
D.E.dA.N., E.Y.C., X.D., H.-M.L., A.S.C., K.L.B., H.I., C.P., A.A.-Y., C.T., S.K. and S. Madireddi
processed and prepared samples for sequencing and provided valuable discussion and
analysis. Y.-J.J.C., L.D.G., S. Madireddi, P.E.dA. and Z.M. optimized and performed single-
cell RNA and TCR sequencing and processing. W.E.O’G., S. Mariathasan, M.B., P.C., M.D.T.,
M.A.H. and I.E. managed biomarker data collection from clinical trials. R. Banchereau
conceived and analysed association with clinical data. T.D.W., L.D., R. Bourgon, I.M. and
J.L.G. contributed to discussions and writing of the manuscript. All authors reviewed and
approved the final version.
Competing interests All authors are employees of Genentech, which develops and markets
drugs for profit.Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-020-
2056-8.
Correspondence and requests for materials should be addressed to T.D.W. or J.L.G.
Peer review information Nature thanks Xiang Chen, Xiaole Shirley Liu and the other,
anonymous, reviewer(s) for their contribution to the peer review of this work.
Reprints and permissions information is available at http://www.nature.com/reprints.