NOTE: HTA data is currently organized by the original publication. As these data are incorporated into multi-functional Atlases, search and other means of accessing data will be added.

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

Lin, J.-R., Wang, S., Coy, S., Tyler, M., Yapp, C., Chen, Y.-A., Heiser, C.N., Lau, K.S., Santagata, S., Sorger, P.K.

Manuscript Submitted

Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells that invade adjacent tissue and spread to distant sites. Here we use highly multiplexed tissue imaging, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. We find that a thorough spatial analysis requires imaging the entire tumor region, not small fields of view (e.g. those found in tissue microarrays). When this condition is met, the data reveal frequent transitions between histological archetypes (tumor grades and morphologies) correlated with molecular gradients. At the tumor invasive margin, where tumor, normal, and immune cells compete, localized features in 2D such as tumor buds and mucin pools are seen in 3D to be large connected structures having continuously varying molecular properties. Immunosuppressive cell-cell interactions also exhibit graded variation in type and frequency. Thus, whereas scRNA-Seq emphasizes discrete changes in tumor state, whole-specimen imaging reveals the presence of large- and small-scale spatial gradients analogous to those in developing tissues.

bioRxiv

HTA CRC Atlas 1

The HTA CRC Atlas 1 dataset contains images and other data being used for construction of an atlas of human colorectal cancer under the auspices of the Human Tumor Atlas Network. Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells that invade adjacent tissue and spread to distant sites. We use highly multiplexed tissue imaging, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. This includes the tumor invasive margin, where tumor, normal, and immune cells compete and were diverse immunosuppressive environments are found.

Contents

Data Explorations

Data image
Multiplexed 3D atlas of state transitions and immune interactions in colorectal cancer (Graphical Abstract)
Data image
CRC01 - introduction - Lin, Wang, Coy et al., 2021

Data Overviews

NOTE! These Data Overviews provide access to minimally processed Level 2 images with no annotation or quality control. Click any of the following thumbnail images for an interactive view of the full-resolution images.

Data image
CRC01 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC01 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC02 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC02 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC03 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC03 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC04 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC04 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC05 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC05 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC06 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC06 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC07 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC07 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC08 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC08 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC09 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC09 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC10 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC10 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC11 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC11 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC12 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC12 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC13 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC13 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC14 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC14 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC15 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC15 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC16 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC16 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC17 - H&E - overview - Lin, Wang, Coy et al., 2021
Data image
CRC17 - overview - Lin, Wang, Coy et al., 2021
Data image
CRC18 - H&E - overview - Lin, Wang, Coy et al., 2021

About Minerva

Exploring the primary image data in Lin-Wang-Sorger et al.

The images in Lin et al. (2021) comprise a ~4.5 TB dataset with some images as large as 1 gigapixel. We provide access to this information without restriction (as required by the NCI Moonshot effort) but it is not in a convenient form for reviewers or general users to explore. The open source Minerva software was designed for the Human Tumor Atlas Network (HTAN) by the Laboratory of Systems Pharmacology to address this problem.

Minerva enables intuitive real-time exploration of very large (gigapixel) high-plex images in the cloud using a web browser. With Minerva, users can pan around and magnify areas of an image and switch between channels. Minerva does not require the installation of any software and is therefore secure; browsing is also anonymous. Users interested in the tool are welcome to explore the documentation, the software publication, and a description of digital docents in general.

We provide two types of Minerva stories with this paper:

  1. Data Explorations” are like museum guides and exploit the digital docents in Minerva to guide readers through the complexities of a large image dataset via a series of narrated stories and waypoints. Both written and audio narration are supported, as well as free exploration. These will be linked to individual figure panels in the final manuscript.
  2. Data Overviews” provide access to minimally processed Level 2 images with annotation and interpretation kept to a bare minimum.