David E Sanin

Hot from the presses!

Laura Sena's @laurasenamd.bsky.social team at at Johns Hopkins working hard to expand the toolkit to treat patients with prostate cancer! Super excited to see out:
doi.org/10.1158/0008...

This study was made possible by the support of the PCF @pcf-science.bsky.social

This study was only made possible with the incredible support of the Prostate Cancer Foundation @pcf-science.bsky.social

Excited to dig into this!!!

The Social Security Administration wants to share your data with the Department of Homeland Security. You might have something to say about that, and if you do, comment here:

https://www.federalregister.gov/documents/2025/11/12/2025-19849/privacy-act-of-1974-system-of-records

q.e.d Science Critical Thinking AI for constructive criticism and science evaluation

Just tried q.e.d. by @odedrechavi.bsky.social et al. with a few papers including by myself & others where I knew a claim within was flawed based on a misunderstanding of the signal.

1) it was impressive. I see what the hype is about.
2) it hallucinated.

www.qedscience.com

Overly long #SciPub🧵 1/n

I love this tool and recommend it to anyone working with single cell data!

This work is the first publication from my lab and I could not be more proud!!!!
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Transcriptional shifts in scRNAseq revealed through Missingness OAR (observed at random) score is a measure of transcriptional shifts among cells, allowing cell prioritization for downstream applications. For best results, test a group of similar cells where you e...

We provide lots more details about this in our pre-print and helpful examples on how to run this for yourself in your own data using our package (sanin-lab.github.io/OARscRNA/).
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We also use this method to predict how Dictyostelium discoideum changes their mitochondrial biology to go from an amoeba to multi-cellular aggregates! (Mitochondrial function sensing dye on the right lights up when cells aggregate and mitochondria lower membrane potential).
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UMAP of plasmacytoid DCs showing OAR scores at the top and expression of 3 type I IFN genes and one solute carrier gene at the bottom. High OAR scores are associated with high expression of selected genes.

For example, in these plasmacytoid DCs, the transcriptional shift we detect is because of type I IFN production!
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Diagnostic Test for Realized Missingness in Mixed-type Data - Sankhya B A frequent concern in analyzing incomplete multivariate measurements in mixed categorical and quantitative scales is whether missing completely at random (MCAR) is an appropriate model. Realized MCAR ...

Cells where missing data patterns are not good predictors, score HIGHER because they have transcriptional programs that are different and therefore you should go and study why!
We are borrowing from statistical methods that examine missingness: doi.org/10.1007/s135...
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Missing data patterns are used to group genes within each cell and the distribution of those groupings is examined for homogeneity. A score is calculated based on a statistical test that determines how well the patterns explain gene expression.

2️⃣ We examine how well missing data patterns explain gene expression and derive a score from this result.
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A matrix of raw counts from single cell RNA sequencing data is converted into a binary matrix with 0s and 1s, where patterns of co-expression (also referred to as missing data patterns) are extracted.

An OAR (Observed At Random) score links co-expression patterns and gene expression. A high OAR score indicates a poor prediction (an interesting cell!).
Our method has 2 main steps:
1️⃣ We define a set of co-expression patterns based on zero-counts, which we call missing data patterns.
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Missing data in single-cell transcriptomes reveals transcriptional shifts Profiling thousands of single cell transcriptomes is routine, yet cell prioritization based on response to biological perturbations is challenging and confounded by clustering, normalization and dimen...

🚨 Want to find interesting cells in single-cell RNAseq data independently of clusters? Try our method to identify transcriptional shifts using OAR scores!
Pre-print: doi.org/10.1101/2025...
R tool and tutorials: sanin-lab.github.io/OARscRNA/
@biorxiv-bioinfo.bsky.social
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Regulation of inflammatory responses by pH-dependent transcriptional condensates BRD4 functions as an intracellular pH sensor through a conserved histidine-rich intrinsically disordered region. Inflammation-associated acidification triggers a pH-dependent switch in transcriptional...

Interesting study showing macrophage gene regulation in response to cellular pH changes!

www.cell.com/cell/fulltex...

Stimulating immune cells in vitro is a common experimental lab model. We profiled 150K blood immune cells treated with 11 different stimuli to compare the effects. The data are freely available for researchers. See the preprint for our findings and to access the data 🧪 doi.org/10.1101/2025...

Cover of George Takei’s They Called Us Enemy” showing a young Japanese American boy in a line of people being sent to an internment camp guarded by a uniformed American soldier

Meant to mention this last week, but if you have a young person in your life who’s into history or graphic novels or just good books, buy them George Takei’s “They Called Us Enemy.” My oldest couldn’t put it down.

Research Saves Lives

At Hopkins, we just went live with an expansive website showing the extraordinary value of research, the impact of cuts to research, what's at stake, resources for our research community, etc.

Check it out: researchsaveslives.jhu.edu

CoQ imbalance drives reverse electron transport to disrupt liver metabolism - Nature Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver dis...

This is cool! Electron transport chain imbalance leading to RET and health complications, with evidence in human settings.

www.nature.com/articles/s41...

InterpolAI: deep learning-based optical flow interpolation and restoration of biomedical images for improved 3D tissue mapping Nature Methods - InterpolAI leverages optimal flow-based artificial intelligence to produce synthetic images between pairs of images for diverse three-dimensional image types. InterpolAI is more...

Dream Police alert: InterpolAI for enhanced 3D imaging (CODA, MRI, EM, confocal).

Read about and InterpolAI here: www.nature.com/articles/s41...

NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging NAD depletion in skeletal muscle does not impair tissue integrity and function or accelerate aging, as shown in a mouse model with an 85% decrease in muscle NAD+ levels. Muscle structure, metabolism, ...

This is WILD! 85% reduction in NAD+ and the tissue just functions as if nothing had happened!?!

NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging: Cell Metabolism www.cell.com/cell-metabol...

GitHub - ArcInstitute/xsra: An efficient CLI to extract sequences from the SRA An efficient CLI to extract sequences from the SRA - ArcInstitute/xsra

Extracting @NCBI SRA files with fasterq-dump can require 17x the size of the accession while decompressing. Our new tool xsra extracts sequences at 5x throughput with significantly less disk usage, built-in compression, and optional BINSEQ outputs

github.com/arcInstitute...

Opinion | To Understand Global Migration, You Have to See It First (Gift Article) These estimates, drawn from the location data of three billion Facebook users, provide a view of human migration in extraordinary detail.

The power of data!!! Dispassionately analyzed and meaningfully visualized!!!

Just wow!!

www.nytimes.com/interactive/...

This integrated method shows how misleading traditional 2D assessments of immune cells localization in tissues is misleading.

3D assessments are a must.

Opinion | Musk Said No One Has Died Since Aid Was Cut. That Isn’t True. (Gift Article) A journey through the front lines of global poverty shows that when the world’s richest men slash aid for the world’s poorest children, the result is sickness, starvation and death.

Over the past few decades the world has collectively reduced poverty and disease at an outstanding rate! Collectively, we should continue doing that! There is no other moral position.

www.nytimes.com/interactive/...

Thanks to everyone for a fantastic meeting #SACB2025 @cancersysbio.bsky.social

(I sure needed an injection of great science in *these times*)

@mathcancer.bsky.social closing out the show...

I'm co-organizing a Cell Symposia on Metabolites in Organellar Communication with @robzonculab.bsky.social, Kivanc Birsoy, and Allyson Evans (@cp-cellmetabolism.bsky.social). It will be in Sitges May 11-13. Submit an abstract by Feb 14. Hope to see you in Spain! cell-symposia.com/metabolites-...

The #SACB2025 immunology session closes out with @davidesanin.bsky.social discussing myeloid cell regulation in prostrate cancer

Enjoying day one of #SACB2025! Amazing line up of speakers today!! Good reminder of the amazing communities of scientists using all kinds of tools and working towards helping patients with cancer!