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Multiparameter persistent homology landscapes identify immune cell spatial patterns in tumors

Abstract:
Highly resolved spatial data of complex systems encode rich and nonlinear information. Quantification of heterogeneous and noisy data—often with outliers, artifacts, and mislabeled points—such as those from tissues, remains a challenge. The mathematical field that extracts information from the shape of data, topological data analysis (TDA), has expanded its capability for analyzing real-world datasets in recent years by extending theory, statistics, and computation. An extension to the standard theory to handle heterogeneous data is multiparameter persistent homology (MPH). Here we provide an application of MPH landscapes, a statistical tool with theoretical underpinnings. MPH landscapes, computed for (noisy) data from agent-based model simulations of immune cells infiltrating into a spheroid, are shown to surpass existing spatial statistics and one-parameter persistent homology. We then apply MPH landscapes to study immune cell location in digital histology images from head and neck cancer. We quantify intratumoral immune cells and find that infiltrating regulatory T cells have more prominent voids in their spatial patterns than macrophages. Finally, we consider how TDA can integrate and interrogate data of different types and scales, e.g., immune cell locations and regions with differing levels of oxygenation. This work highlights the power of MPH landscapes for quantifying, characterizing, and comparing features within the tumor microenvironment in synthetic and real datasets.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1073/pnas.2102166118

Authors


Publisher:
National Academy of Sciences
Journal:
Proceedings of the National Academy of Sciences of USA More from this journal
Volume:
118
Issue:
41
Article number:
e2102166118
Publication date:
2021-10-08
Acceptance date:
2021-08-24
DOI:
EISSN:
1091-6490
ISSN:
0027-8424


Language:
English
Keywords:
Pubs id:
1194154
Local pid:
pubs:1194154
Deposit date:
2021-09-17
ARK identifier:

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