iiinova — where your digital self keeps evolving

Reposted by Noah F. Greenwald

Erin McCaffrey, PhD @erin-mccaffrey.bsky.social · 24/02/2025

Happy to share a preprint from the Angelo lab many years in the making. Read on for a saga of multiplexed imaging, immunometabolism, and TB granulomas with some fun side quests into the realms of geographical information sciences and transcriptomics… (1/20) doi.org/10.1101/2025...

doi.org

The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control

Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium tuberculosis (Mtb) infection and support bacterial persistence. We prev...

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Noah F. Greenwald @noahgreenwald.bsky.social · 07/02/2025

We developed a dedicated pipeline for mibi data: github.com/angelolab/to..., but for other data modalities I’m not as familiar what people generally do. Right now there isn’t a good cross platform solution for data normalization, at least not that we’ve found

github.com

GitHub - angelolab/toffy: Scripts for interacting with and generating data from the commercial MIBIScope

Scripts for interacting with and generating data from the commercial MIBIScope - angelolab/toffy

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Noah F. Greenwald @noahgreenwald.bsky.social · 30/01/2025

Great point. We spent a lot of effort addressing batch effects earlier in our processing pipeline so that SpaceCat wouldn't have to deal with them. In general, I would say the earlier you can address your batch correction issues, the better, but there aren't as many options for spatial data

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

If you run into any problems getting the codebase to work, have questions about what we found, or want to chat, please don’t hesitate to reach out (/end) bsky.app/profile/noah...

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

This wouldn’t have been possible without an amazing team (most of whom have not migrated over to the good place yet!), including Iris, Cami, Seongyeol, Manon, as well as Christina, Marleen and Mike (9/x)

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

This was just a sampling of what we found; for the full details, please check out the paper, as well as our github, where we’ve made all the underlying code open source and available (8/x) github.com/angelolab/Sp...

github.com

GitHub - angelolab/SpaceCat: Generate a spatial catalogue from multiplexed imaging data

Generate a spatial catalogue from multiplexed imaging data - angelolab/SpaceCat

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

Finally, to look at how these features could be combined together, as well as to compare modalities, we built multivariate models to predict outcome from each data type at each timepoint. We found large differences across both assay types and sample timepoints! (7/x)

Evaluation of multivariate models trained on different timepoints (x axis) and data types (colors) to predict patient outcome.

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

When we looked at the specific features we defined, we found some that were temporally dependent, with good predictive power at one timepoint but poor predictive power at another timepoint (6/x)

The same feature (T / Cancer Ratio) has no association with outcome when looking at the primary tumor, but very strong association with outcome when looking at the on treatment (on-nivo) sample

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

We then tested which of the 800+ features from SpaceCat could predict response to immunotherapy, finding numerous strong predictors. Interestingly, features defined in specific regions of the tumor did an especially good job at predicting outcome (5/x)

Volcano plot on the left showing association with outcome for each of the SpaceCat features. Barplot on the right shows the enrichment in top predictive features for those defined within specific regions (compartments) of the tumor

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

To help us make sense of this spatially-resolved data, we built SpaceCat, an algorithm to quantify and summarize the key features from spatial datasets. SpaceCat can be applied to processed imaging data from any multiplexed imaging platform! (4/x)

Summary of the types of features that SpaceCat generates, with representative images from four of the categories

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

We then generated highly multiplexed imaging data using an antibody panel of 37 antibodies. This allowed us to identify 22 cell types across the more than 650 TMA cores we imaged from 117 total patients (3/x)

Heatmap showing the cell types identified in our study. Each row is a cell type, and each column is a different marker on the antibody panel

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Noah F. Greenwald @noahgreenwald.bsky.social · 29/01/2025

Our awesome collaborators at NKI put together a unique cohort spanning primary disease, pre-treatment metastases, and on-treatment metastases from triple negative breast cancer patients enrolled in the TONIC clinical trial (2/x)

Cartoon overview of the samples collected from patients at each timepoint, as well as the number of different modalities (MIBI, DNA, RNA) collected from each.

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Reposted by Noah F. Greenwald

Anshul Kundaje @anshulkundaje.bsky.social · 24/01/2025

I wanted to write briefly about a very pleasant experience we recently had coordinating and collaborating closely on competing publications with 2 other teams. 1/

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Noah F. Greenwald @noahgreenwald.bsky.social · 24/01/2025

Hi Erik, I work on tissue imaging, spatial biology, and cancer research. Could you please add me to the feed? Thanks!https://scholar.google.com/citations?user=ajvnimEAAAAJ&hl=en

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Reposted by Noah F. Greenwald

Arjun Raj @arjunraj.bsky.social · 12/12/2023

Reposting our Penn Postdoctoral Fellowship in Genetics! www.med.upenn.edu/apps/my/bpp_...

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Noah F. Greenwald @noahgreenwald.bsky.social · 01/10/2023

Hi all, I just joined! I’m a PhD student at Stanford studying tumor immunology. Excited to try this thing out #HiSciSky #AcademicSky

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