labsyspharm/CRC_atlas_2022
Year: 2023
Type: software
Abstract: Multiplexed 3D atlas of state transitions and immune interactions in colorectal cancer Jia-Ren Lin1,2,*, Shu Wang1,2,3,*, Shannon Coy1,2,4,*, Yu-An Chen1,2, Clarence Yapp1,2, Madison Tyler1,2, Maulik K. Nariya1,2,7, Cody N. Heiser1,5, Ken S. Lau1,6, Sandro Santagata1,2,4,7,†, and Peter K. Sorger1,2,7,#,† *These (first) authors contributed equally †These (senior) authors contributed equally 1 Human Tumor Atlas Network 2 Ludwig Center at Harvard and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA. 3 Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA. 4 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 5 Program in Chemical & Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. 6 Epithelial Biology Center and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. 7 Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA. SUMMARY Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells characterized by high intratumoral variation. We use highly multiplexed tissue imaging, 3D reconstruction, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. Quantitation of these features in high-plex marker space reveals recurrent transitions from one tumor morphology to the next, some of which are coincident with long-range gradients in the expression of oncogenes and epigenetic regulators. At the tumor invasive margin, where tumor, normal, and immune cells compete, T-cell suppression involves multiple cell types and 3D imaging shows that seemingly localized 2D features such as tertiary lymphoid structures are commonly interconnected and have graded molecular properties. Thus, while cancer genetics emphasizes the importance of discrete changes in tumor state, whole-specimen imaging reveals large-scale morphological and molecular gradients analogous to those in developing tissues. DATA AVAILABILITY AND ATLAS IMAGE VIEWING As part of this paper all images at full resolution, all derived image data (e.g., segmentation masks) and all cell count tables have been released via the NCI-sponsored repository for Human Tumor Atlas Network (HTAN; https://htan-portal-nextjs.vercel.app/). Because the public resource is still undergoing extensive development, an additional version of the numerical data is also available at https://www.synapse.org/#!Synapse:syn18434611/wiki/597418. Several of the figure panels in this paper are available with text and audio narration for anonymous on-line browsing using MINERVA software (Rashid et al., 2022), which supports zoom, pan, and selection actions without requiring the installation of software. A Minerva story with an overview of CRC1 (sections 096 and 097) can be found at: cycif.org/crc1-intro and the 25 CRC1 Z-sections can be found at: cycif.org/crc1-3d. The third Minerva story focused on data integration for CRC1 can be found at: https://www.cycif.org/data/lin-wang-coy-2021/viz.html. Other resources, including images of CRC2-17, for this paper can be found at https://www.tissue-atlas.org/atlas-datasets/lin-wang-coy-2021/. We will make all of these MINERVA stories available directly via the published version of this paper; we are currently securing DOIs for these stories to provide a more uniform name space. Funding This work was supported by NIH grants U54-CA225088 (PKS, SS), U2C-CA233280 (PKS, SS), U2C-CA233262 (PKS, SS), U2C-CA233291 (CNH, KSL), R01-DK103831 (CNH, KSL), NIH training grant T32-GM007748 (SC), and the Ludwig Center at Harvard (PKS, SS). All HTAN consortium members are named at humantumoratlas.org. Development of computational methods was supported by the Ludwig Cancer Research, by a Team Science Grant from the Gray Foundation, and by the David Liposarcoma Research Initiative. We thank Dana-Farber/Harvard Cancer Center for the use of the Specialized Histopathology Core, which provided histopathology services supported by P30-CA06516.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4393796463