Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer

Lin, Jia-Ren; Wang, Shu; Coy, Shannon; Yuan, Chen; Yapp, Clarence; Tyler, Madison; Nariya, Maulik K.; Heiser, Cody N.; Lau, Ken S.; Santagata, Sandro; Sorger, Peter K.

doi:10.1016/j.cell.2022.12.028

Cited by 135 publications

(126 citation statements)

References 82 publications

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“…Inspection of images from IFM2 tumors exhibiting slow progression (e.g., patient C34) revealed high-levels of PD-L1 + cells ( Fig. 4h , yellow) adjacent to pan-cytokeratin positive tumor cells (green); based on overlap of PD-L1 + ,CD68 and CD45 staining we conclude that PD-L1 + cells are likely myeloid in origin, as described previously 22 . In C34, -SMA stained tumor proximate stromal cells – most likely fibroblasts – were also well-infiltrated with CD4 + T cells.…”

Section: Resultssupporting

confidence: 79%

“…3c). We have previously observed a similar fraction of "unidentifiable" cells following 40-60 plex CyCIF imaging 22 and surmised that these cells were either negative for all antibody markers included in the panel or had morphologies that are difficult to segment 50 .…”

Section: Integrated Analysis Of If and Hande Imagesmentioning

confidence: 76%

“…Tissue-based cyclic immunofluorescence (CyCIF) was performed as previously described 15 following the methods available in protocols.io ( dx.doi.org/10.17504/protocols.io.bjiukkew ). Data from specimens C1-C17 was acquired as previously reported 22 and computed cell counts were compared in this study with cell counts derived from Orion images of adjacent sections from the same specimens. A BOND RX Automated Slide Stainer was used to bake FFPE slides at 60°C for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…Latent Dirichlet Allocation (LDA) was used to compute spatial neighborhoods as described 22 . First, each sample was divided into “grids” of 200 microns 2 , and marker frequency was calculated in each grid.…”

Section: Methodsmentioning

confidence: 99%

“…Many high-plex imaging studies performed to date on human cohorts involve tissue microarrays (TMAs; arrays of many 0.3 to 1 mm specimens on a single slide) or the small fields of view characteristic of mass-spectrometry based imaging 9, 11 . However, whole-slide imaging is required for clinical research and for diagnosis, both to achieve sufficient statistical power 22 and as an FDA requirement 23 .…”

Section: Introductionmentioning

confidence: 99%

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Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

Lin

Yuan

Campton

et al. 2022

Preprint

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Precision medicine is critically dependent on better methods for diagnosing and staging disease and predicting drug response. Histopathology using Hematoxylin and Eosin (H&E) stained tissue, not genomics, remains the primary diagnostic modality in cancer. Moreover, recently developed, highly multiplexed tissue imaging represents a means of enhancing histology workflows with single cell mechanisms. Here we describe an approach for collecting and analyzing H&E and high-plex immunofluorescence (IF) images from the same cells in a whole-slide format suitable for translational and clinical research and eventual deployment in diagnosis. Using data from 40 human colorectal cancer resections (60 million cells) we show that IF and H&E images provide human experts and machine learning algorithms with complementary information. We demonstrate the automated generation and ranking of computational models, based either on immune infiltration or tumor-intrinsic features, that are highly predictive of progression-free survival. When these models are combined, a hazard ratio of ~0.045 is achieved, demonstrating the ability of multi-modal digital pathology to generate high-performance and interpretable biomarkers.

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Section: Resultssupporting

confidence: 79%

Section: Integrated Analysis Of If and Hande Imagesmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

Lin

Yuan

Campton

et al. 2022

Preprint

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Engineering the future of 3D pathology

Liu,

Chow,

Colling

et al. 2023

The Journal of Pathology CR

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In recent years, technological advances in tissue preparation, high‐throughput volumetric microscopy, and computational infrastructure have enabled rapid developments in nondestructive 3D pathology, in which high‐resolution histologic datasets are obtained from thick tissue specimens, such as whole biopsies, without the need for physical sectioning onto glass slides. While 3D pathology generates massive datasets that are attractive for automated computational analysis, there is also a desire to use 3D pathology to improve the visual assessment of tissue histology. In this perspective, we discuss and provide examples of potential advantages of 3D pathology for the visual assessment of clinical specimens and the challenges of dealing with large 3D datasets (of individual or multiple specimens) that pathologists have not been trained to interpret. We discuss the need for artificial intelligence triaging algorithms and explainable analysis methods to assist pathologists or other domain experts in the interpretation of these novel, often complex, large datasets.

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Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.

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Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer

Cited by 135 publications

References 82 publications

Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

Engineering the future of 3D pathology

Three‐dimensional genome structure and function

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