The tumor microenvironment (TME) plays a critical role in cancer progression and therapeutic response. New single cell and imaging technologies provide unprecedented measurements of cell type composition, subtypes of common cell types in disparate states, interactions between neighboring cells, and T cell function. However, each of these components of the TME are captured by disparate measurement technologies. Both new computational methods and software for multi-platform data integration are essential to characterize the TME. Therefore, we propose a unified R/Bioconductor package TMEMap for multi-platform single cell data integration.
Aim 1 will integrate single cell RNA-sequencing and single cell TCR-sequencing data to distinguish T cell function in distinct T cell subtypes and states.
Aim 2 will integrate combined single cell RNA-sequencing and protein from CITE-seq with imaging proteomics for digital pathology to map cellular interactions in the TME.
Aim 3 will further the disseminate this software with through GenePattern Notebook. This workflow will be developed in collaboration with clinical investigators to ensure usability and interpretability of the visualization methods using clinical biospecimens from synergistic studies. Altogether, this software will provide a strong foundation for future work embedding these methods in a database for multi-platform single cell data to automatically perform comprehensive TME characterization in large scale NCI profiling efforts such as the Human Tumor Atlas Network.

Public Health Relevance

The tumor microenvironment (TME) plays a critical role in cancer progression and therapeutic response. New single cell and imaging technologies yield unprecedented measurements to characterize these states. We propose software and workflows for single cell data integration to characterize the TME.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA253403-01
Application #
10058504
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Li, Jerry
Project Start
2020-09-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205