CONFLICTS OF INTEREST
S.R. has received research support from Genentech. A.T.M. and S. Bodapati are cofounders of, U.T. is an employee of, and C.M.S. is a scientific advisor to Enable Medicine, LLC. G.P.N. has equity in and is a scientific board member of Akoya Biosciences, Inc. B.S.B has received research grants from Prometheus Biosciences and consulting fees from Pfizer, Bristol Myers Squibb, and Takeda unrelated to this topic. S.E.S. has received consulting fees from Prometheus Biosciences, Pfizer, Takeda, Gilead, Janssen, Celgene, and Surrozen unrelated to this topic. W.J.S. has received research grants from Abbvie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, Theravance Biopharma; consulting fees from Abbvie, Abivax, Admirx, Alfasigma, Alimentiv (Robarts Clinical Trials, owned by Health Academic Research Trust [HART]), Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vedanta Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences. Spouse: Iveric Bio - consultant, stock options; Progenity - stock; Oppilan Pharma - consultant, stock options; Prometheus Biosciences - employee, stock options; Ventyx Biosciences – stock options; Vimalan Biosciences – stock options. The other authors declare no competing interests.
Conceptualization: A.T.M., C.M.S., and S.R.; Methodology: A.T.M., S. Black, C.M.S., and S.R.; Software: A.T.M., U.T., J.C., G.L.B., and S.S.B.; Validation: S. Black and C.M.S.; Formal Analysis: A.T.M., D.R.H., and C.M.S.; Investigation: A.T.M., D.R.H., C.M.S., and S.R.; Resources: E.C.C., S. Bodapati, J.C., S.E.S., B.S.B., W.S.J., J.T.C., and S.R.; Writing - Original Draft: A.T.M., D.R.H., C.M.S., and S.R.; Writing - Review and Editing: A.T.M., D.R.H., S.S.B., B.S.B., J.T.C., G.P.N., C.M.S., and S.R.; Supervision: C.M.S. and S.R.; Project Administration: E.C.C.; Funding acquisition: S.S.G., G.P.N., C.M.S., and S.R.
We thank the patients for their consent to use their tissues for research. This work was primarily supported by the Kenneth Rainin Foundation (2018 − 575 to S.R.). Further support was provided by the US National Institutes of Health (2U19AI057229-16, 5P01HL10879707, 5R01GM10983604, 5R33CA18365403, 5U01AI101984-07, 5UH2AR06767604, 5R01CA19665703, 5U54CA20997103, 5F99CA212231-02, 1F32CA233203-01, 5U01AI140498-02, 1U54HG010426-01, 5U19AI100627-07, 1R01HL120724-01A1, R33CA183692, R01HL128173-04, 5P01AI131374-02, 5UG3DK114937-02, 1U19AI135976-01, IDIQ17X149, 1U2CCA233238-01, 1U2CCA233195-01 to G.P.N.) and by the NIDDK-funded San Diego Digestive Diseases Research Center (P30DK120515). C.M.S. was supported by the Swiss National Science Foundation (P300PB_171189, P400PM_183915). S.S.B. was supported by a Stanford Bio-X Interdisciplinary Graduate Fellowship and Stanford’s Bioengineering Department. G.L.B was supported by an NIH T32 Fellowship (5T32AI007290-34).