iiinova — where your digital self keeps evolving

Micha Sam Brickman Raredon @msbr89.bsky.social · 22/09/2026

Here is the response I was sent by @nytimes.com re: their communication with Nikon; it also doesn’t address the main critiques.

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Micha Sam Brickman Raredon @msbr89.bsky.social · 13/02/2026

"Lysophosphatidic acid and sphingosine-1- phosphate are apical polarity cues in multiple organoid systems" 🔥🔥👀 www.cell.com/action/showP...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

Our landing point has been to visualize these connectivity fields as three-dimensional surfaces that you can rotate in space! Here are a few selected fields from a single location in a mouse embryo capturing the developing ribs, lung, and diaphragm: Interactive HTML: figshare.com/s/2f66def6d2...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

This lead us down a beautiful rabbit-hole experimenting with the relationship between high-dimensional connectivity and the resolution of spatial tissue domains. Note that in all of these graphs, we are exclusively studying ligand-receptor information, no intracellular genes:

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

To evaluate, we needed to quantify the high-dimensional structure of these 'connectivity fields'. So, we performed unsupervised clustering and measured the number and the spatial entropy (coherence) of the resulting groups. We found that a stoichiometrically-informed convolution maximized structure:

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

But this modeling was done on the ligand and the receptor individually. We wanted to predict density fields for ligand-receptor binding! We therefore experimented with ways of convolving these outputs, comparing established methods with next-gen ideas informed by ligand-receptor binding kinetics:

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

But how to approach? There are many well-established spatial statistical models for data with exactly this form. We tested and compared three in particular: a Poisson, Zero-Inflated Poisson (ZIP), and Zero-Adjusted Poisson (ZAP), and found that the Poisson model was the top performing:

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

For one, we realized almost immediately that we needed to think carefully about what data to use as input. Most single-cell and spatial pipelines use count-normalized data. But we learned that this was likely not the best starting point for the tissue-scale modeling we had in mind.

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

If handled thoughtfully, we realized that these count values could be used to infer continuous fields estimating local ligand density, local receptor density, and the local probability of ligand-receptor binding events. We had a loose plan, but many questions about specifics...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

We found ourselves particularly interested in modeling local ligand-receptor interaction probability densities. This is because these data have a wealth of information regarding omics-level (high-dimensional) ligand and receptor transcription, in space:

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

There are many things that we can think about measuring and modeling spatially using these types of data. Aaron and I have now had years of conversations about the different ways researchers might approach these data and the pros/cons of applying different perspectives.

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

We were interested in seeing if we could use spatial statistics, well developed in geospatial statistics, to study morphogenic interactions in living tissues. Spatial-omics methods are now producing rich datasets across entire tissues and organisms, allowing tissue-scale analysis:

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

In the body, there are many forms of cellular input and output. Cells sense their environments, process this information in a state-dependent way, and then respond accordingly. These input/output loops are major drivers of tissue development and regulators of collective cellular behavior.

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/12/2025

20 years ago, Aaron Osgood-Zimmerman and I would entertain ourselves asking questions like, "How many crickets are in field?" or "How many cells are in the body?" Aaron became a statistician, and I become a biologist. We have now collaborated on an interesting exploration: doi.org/10.64898/202...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 01/10/2025

United States Disappeared Tracker public.tableau.com/views/United...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 02/09/2025

"Single cell RNA seq reveals the pro-regenerative phenotype of thrombospondin-2 deficient dermal fibroblasts" www.nature.com/articles/s41... Amazing work from Huang et al!

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Micha Sam Brickman Raredon @msbr89.bsky.social · 22/08/2025

'Single cell decomposition of multicellular aging programs associated with impaired lung regeneration' www.biorxiv.org/content/10.1...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 22/08/2025

'p53 maintains lineage fidelity during lung capillary injury-repair in neonatal hyperoxia' insight.jci.org/articles/vie...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 02/08/2025

United States Disappeared Tracker public.tableau.com/views/United...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 02/08/2025

"The interplay between biomechanics and cell kinetics explains the spatial pattern in liver fibrosis" www.biorxiv.org/content/10.1...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 23/06/2025

"thinking for yourself is a frictional activity not a statistical correlation. An AI-mediated essay plan has already missed the point by bypassing the student's own capacity to develop and substantiate propositions about the world." from @danmcquillan.bsky.social danmcquillan.org/cpct_seminar...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 23/06/2025

OMG I am so glad someone finally did this. Thank you 🙏 @lelandmcinnes.bsky.social This will now consume hours and hours of my time. lmcinnes.github.io/datamapplot_...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 15/06/2025

United States Disappeared Tracker public.tableau.com/views/United...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 14/06/2025

United States Disappeared Tracker public.tableau.com/views/United...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 09/06/2025

United States Disappeared Tracker public.tableau.com/views/United...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 07/06/2025

United States Disappeared Tracker public.tableau.com/views/United...

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Micha Sam Brickman Raredon @msbr89.bsky.social · 04/06/2025

"Addition of RSPO1 induced patterning of distalized nephrons, including distal convoluted tubule and thick ascending limb of loop of Henle ... This in vitro continuum ... illustrates the role of the microenvironment in cellular identity." www.biorxiv.org/content/10.1...