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Biological Sciences - Article
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Ulcerative colitis is a chronic-relapsing inflammatory disease of the large intestine with a complex, multifactorial pathogenesis. TNF inhibitors are widely used to suppress immune-mediated tissue damage in ulcerative colitis patients; however, therapy failures are common. Predicting TNF inhibitor response requires an understanding of the architectural features that underlie mucosal inflammation and those responsible for resistance. Here, we used highly multiplexed immunofluorescence to uncover the spatially resolved tissue architectures underlying disease progression and treatment response in 42 tissue regions from 34 individuals. We created a tissue atlas and performed spatial analysis to identify cell-cell contacts and cellular neighborhoods. We observed that cellular functional states depend on cellular neighborhood and that a subset of inflammatory cell types and cellular neighborhoods in ulcerative colitis patients persisted even during treatment with TNF inhibitor, indicating resistant niches. A computer vision model, with no a priori assumptions regarding cellular architectural features, was able to predict TNF inhibitor resistance. This spatial model significantly outperformed classification models based on single-cell data alone. Our results demonstrate the value of a spatial tissue atlas as a precision medicine tool to guide treatment of patients suffering from autoimmune diseases.
Keywords
Ulcerative colitis, cellular neighborhoods, CODEX, multiplexed imaging, tissue architecture, TNF inhibitors, therapy prediction, autoimmune disease
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- IBDPrecisionMedicineCODEXSupplement1.docx
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Biological Sciences - Article
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Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 03 Feb, 2021
No community comments so far
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Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Ulcerative colitis is a chronic-relapsing inflammatory disease of the large intestine with a complex, multifactorial pathogenesis. TNF inhibitors are widely used to suppress immune-mediated tissue damage in ulcerative colitis patients; however, therapy failures are common. Predicting TNF inhibitor response requires an understanding of the architectural features that underlie mucosal inflammation and those responsible for resistance. Here, we used highly multiplexed immunofluorescence to uncover the spatially resolved tissue architectures underlying disease progression and treatment response in 42 tissue regions from 34 individuals. We created a tissue atlas and performed spatial analysis to identify cell-cell contacts and cellular neighborhoods. We observed that cellular functional states depend on cellular neighborhood and that a subset of inflammatory cell types and cellular neighborhoods in ulcerative colitis patients persisted even during treatment with TNF inhibitor, indicating resistant niches. A computer vision model, with no a priori assumptions regarding cellular architectural features, was able to predict TNF inhibitor resistance. This spatial model significantly outperformed classification models based on single-cell data alone. Our results demonstrate the value of a spatial tissue atlas as a precision medicine tool to guide treatment of patients suffering from autoimmune diseases.
Figure 1
Figure 2
Figure 3
Figure 4
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- IBDPrecisionMedicineCODEXSupplement1.docx
Supplement
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