A tissue atlas of ulcerative colitis revealing evidence of sex-dependent differences in disease-driving inflammatory cell types and resistance to TNF inhibitor therapy
Aaron T. Mayer, Derek Holman, Anav Sood, Utkarsh Tandon, Salil S. Bhate, Sunil Bodapati, Graham L. Barlow, Jeff Chang, Sarah Black, Erica C. Crenshaw, Alexander N. Koron, Sarah E. Streett, Sanjiv S. Gambhir, William J. Sandborn, Brigid S. Boland, Trevor Hastie, Robert Tibshirani, John T. Chang, Garry P. Nolan, Christian M. Schürch, Stephan Rogalla
Abstract
Although literature suggests that resistance to TNF inhibitor (TNFi) therapy in patients with ulcerative colitis (UC) is partially linked to immune cell populations in the inflamed region, there is still substantial uncertainty underlying the relevant spatial context. Here, we used the highly multiplexed immunofluorescence imaging technology CODEX to create a publicly browsable tissue atlas of inflammation in 42 tissue regions from 29 patients with UC and 5 healthy individuals. We analyzed 52 biomarkers on 1,710,973 spatially resolved single cells to determine cell types, cell-cell contacts, and cellular neighborhoods. We observed that cellular functional states are associated with cellular neighborhoods. We further observed that a subset of inflammatory cell types and cellular neighborhoods are present in patients with UC with TNFi treatment, potentially indicating resistant niches. Last, we explored applying convolutional neural networks (CNNs) to our dataset with respect to patient clinical variables. We note concerns and offer guidelines for reporting CNN-based predictions in similar datasets.