Multiparameter persistent homology landscapes identify immune cell spatial patterns in tumors

Copyright © 2021 the Author(s). Published by PNAS..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:118

Enthalten in:

Proceedings of the National Academy of Sciences of the United States of America - 118(2021), 41 vom: 12. Okt.

Sprache:

Englisch

Beteiligte Personen:

Vipond, Oliver [VerfasserIn]
Bull, Joshua A [VerfasserIn]
Macklin, Philip S [VerfasserIn]
Tillmann, Ulrike [VerfasserIn]
Pugh, Christopher W [VerfasserIn]
Byrne, Helen M [VerfasserIn]
Harrington, Heather A [VerfasserIn]

Links:

Volltext

Themen:

Digital pathology
Histology data
Hypoxia
Journal Article
Research Support, Non-U.S. Gov't
Topological data analysis
Tumor immunology

Anmerkungen:

Date Completed 14.12.2021

Date Revised 14.12.2021

published: Print

Citation Status MEDLINE

doi:

10.1073/pnas.2102166118

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM33166447X