Published January 7, 2025 | Version Published
Journal Article Open

Integrative Co-Registration of Elemental Imaging and Histopathology for Enhanced Spatial Multimodal Analysis of Tissue Sections through TRACE

  • 1. Dartmouth Health, Lebanon, NH 03766, USA
  • 2. ROR icon Dartmouth College
  • 3. ROR icon California Institute of Technology
  • 4. Cupertino High School, Cupertino, CA 95014, USA
  • 5. Langley High School, McLean, VA 22101, USA
  • 6. Thomas Jefferson High School for Science and Technology, Alexandria, VA 22312, USA
  • 7. Liberal Arts and Science Academy, Austin, TX 78721, USA
  • 8. Andover High School, Andover, MA 01810, USA
  • 9. ROR icon University of California, San Francisco
  • 10. ROR icon Cedars-Sinai Medical Center

Abstract

Elemental imaging provides detailed profiling of metal bioaccumulation, offering more precision than bulk analysis by targeting specific tissue areas. However, accurately identifying comparable tissue regions from elemental maps is challenging, requiring the integration of hematoxylin and eosin (H&E) slides for effective comparison. Facilitating the streamlined co-registration of Whole Slide Images (WSI) and elemental maps, TRACE enhances the analysis of tissue regions and elemental abundance in various pathological conditions. Through an interactive containerized web application, TRACE features real-time annotation editing, advanced statistical tools, and data export, supporting comprehensive spatial analysis. Notably, it allows for comparison of elemental abundances across annotated tissue structures and enables integration with other spatial data types through WSI co-registration. Availability and Implementation Available on the following platforms– GitHub: jlevy44/trace_app, PyPI: trace_app, Docker: joshualevy44/trace_app, Singularity: docker://joshualevy44/trace_app. Supplementary information Supplementary data are available.

Copyright and License

© The Author(s) 2025. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 

Funding

This work was supported by the National Institutes of Health [R24GM141194, P20GM104416, and P20GM130454 subawards to J.L.].

Contributions

Yunrui Lu (Writing – original draft, Investigation, Conceptualization, Formal analysis, Software); Serin Han (Formal analysis); Aruesha Srivastava (Formal analysis); Neha Shaik (Formal analysis); Matthew Chan (Formal analysis); Alos Diallo (Investigation); Naina Kumar (Formal analysis); Nishita Paruchuri (Formal analysis); Hrishikesh Deosthali (Formal analysis); Vismay Ravikumar (Formal analysis); Kevin Cornell (Supervision, Data curation); Elijah Stommel (Funding acquisition, Data curation); Tracy Punshon (Supervision, Conceptualization, Data curation, Funding acquisition); Brian Jackson (Supervision, Conceptualization, Data curation, Funding acquisition); Fred Kolling IV (Data curation); Linda Vahdat (Validation); Louis Vaickus (Validation); Jonathan Marotti (Validation); Sunita Ho (Data curation, Supervision); Joshua Levy (Conceptualization, Formal analysis, Supervision, Funding acquisition, Software, Writing – original draft). All authors participated in reviewing and editing of this research work.

Supplemental Material

Supplementary data are available at Bioinformatics Advances online.

Code Availability

  • TRACE was implemented using a Python Dash/Flask front end (Dabbas 2021), Python v3.9.
  • Available on the following platforms—GitHub: jlevy44/trace_app, PyPI: trace_app, Docker: joshualevy44/trace_app, Singularity: docker://joshualevy44/trace_app.

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Additional details

Funding

National Institutes of Health
R24GM141194
National Institutes of Health
P20GM104416
National Institutes of Health
P20GM130454

Dates

Accepted
2025-01-06
Accepted
Available
2025-01-07
Published online
Available
2025-01-18
Corrected and typeset

Caltech Custom Metadata

Publication Status
Published