A Functional Spatial Analysis Platform for Discovery of Immunological Interactions Predictive of Low-Grade to High-Grade Transition of Pancreatic Intraductal Papillary Mucinous Neoplasms.

Cancer Informatics
Souptik BaruaArvind Rao

Abstract

Intraductal papillary mucinous neoplasms (IPMNs), critical precursors of the devastating tumor pancreatic ductal adenocarcinoma (PDAC), are poorly understood in the pancreatic cancer community. Researchers have shown that IPMN patients with high-grade dysplasia have a greater risk of subsequent development of PDAC in the remnant pancreas than do patients with low-grade dysplasia. In this study, we built a computational prediction model that encapsulates the spatial cellular interactions in IPMNs that play key roles in the transformation of low-grade IPMN cysts to high-grade cysts en route to PDAC. Using multiplex immunofluorescent images of IPMN cysts, we adopted algorithms from spatial statistics and functional data analysis to create metrics that summarize the spatial interactions in IPMNs. We showed that an ensemble of models learned using these spatial metrics can robustly predict, with high accuracy, (1) the dysplasia grade (low vs high grade) and (2) the risk of a low-grade cyst progressing to a high-grade cyst. We obtained high classification accuracies on both tasks, with areas under the curve of 0.81 (95% confidence interval: 0.71-0.9) for task 1 and 0.81 (95% confidence interval: 0.7-0.94) for task 2. To the best of o...Continue Reading

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Citations

Mar 5, 2020·International Journal of Cancer. Journal International Du Cancer·Sebastian LundgrenArtur Mezheyeuski
May 3, 2019·Cancer Immunology Research·Sangeetha M ReddyElizabeth A Mittendorf
Nov 6, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vincent BernardHector A Alvarez
Feb 28, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Phyu P AungMichael T Tetzlaff
May 18, 2021·Frontiers in Molecular Biosciences·Sharia HernandezEdwin Roger Parra
Oct 22, 2021·Frontiers in Immunology·Mayank BaranwalArvind Rao

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Software Mentioned

Spotfire
MFPCA
MATLAB
randomForest
R
inForm
R language

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