We thank Piero Pollesello (Orion Pharma, Finland) for editorial coordination among co-authors, Shrestha Roy (Orion Pharma, India) for the graphic renditions, Hughes associates (Oxford, UK) for editorial assistance with the English language, and Alexander J.K. Wilkinson (Respiratory Department, East and North Hertfordshire NHS Trust, Stevenage, UK) for useful discussion.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
There are no restrictions on data access. Raw imaging data from cyclic immunofluorescence experiments are available from the corresponding authors on request. These files are large and may require significant computational pre-processing for final data analysis. The processes used by the authors are delineated in the Methods section and/or code repository ( _coy_spatialcorrelation), but interested parties should first consider using processed counts tables available in the Synapse repository ( !Synapse:syn30803357)63. Source data are provided with this paper.
S.C., M.T., and S.S. developed the concept for the study. J.R.L., R.R., C.Y., and C.C.R. collected image data and performed analysis in collaboration with S.C. and S.W. S.A.S., M.R., G.B. and N.Y.R.A. designed, performed, and analyzed mass spectrometry experiments in collaboration with S.C., G.J.B., and S.S. S.C. and P.K. collected and analyzed single cell RNA-sequencing data. L.S. performed and analyzed T.C.G.A. in collaboration with M.T., S.C., and S.S. T.D.R., M.S., and K.A.C. collected and analyzed C.B.T.T.C. pediatric tumors and data in collaboration with S.C. and S.S. J.H. collected and analyzed clinical and demographic data in collaboration with S.C. All authors wrote and/or edited the manuscript. S.S., P.K.S., N.Y.R.A., P.Y.W., P.B., and K.L.L. provided supervision and funding.
M.T. has a consulting or advisory role with Agios Pharmaceutical, Integragen, and Taiho Oncology, and research funding from Sanofi. P.K.S. is a member of the SAB or BOD member of Applied Biomath, RareCyte Inc., and Glencoe Software; P.K.S. is also a member of the NanoString SAB and a consultant for Montai Health and Merck. In the last five years the Sorger lab has received research funding from Novartis and Merck. KLL is supported by Eli Lilly and BMS, consults for BMS, Integragen, Travera LLC, is on the SAB of Integragen and Rarecyte, and holds equity in Travera LLC. P.B. receives grant funding from Novartis Institute of Biomedical Research and Deerfield, and consults for QED Therapeutics, for unrelated projects. P.Y.W. has research support from Agios, Astra Zeneca, Medimmune, Celgene, Eli Lilly, Genentech, Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Chimerix, Vascular Biogenics, and VBI Vaccines. P.W. is on the advisory boards of Agios, Astra Zeneca, Black Diamond, Boston Pharmaceuticals, Chimerix, CNS Pharmaceuticals, Elevate Bio, Imvax, Karyopharm, Merck, Mundipharma, Novocure, Novartis, Nuvation Bio, Prelude Therapeutics, Vascular Biogenics, VBI Vaccines, Voyager, and QED. RareCyte manufactured instruments used for tissue imaging and Glencoe developed the OMERO Database used for image informatics. P.K.S. and S.S. declare that none of these relationships have influenced the content of this manuscript. The remaining authors declare no competing interests. 2b1af7f3a8