Shih-Feng You

Senior Computational Biologist @ Pfizer | Neuroscience PhD @ WashU | Alzheimer’s disease | microglia | neuroinflammation | opinions are my own

[Shih-Feng You @SFYou614]

Milestone

[NEJM @NEJM]

Presented at #ASCO26:

Among patients with previously treated metastatic pancreatic ductal adenocarcinoma, the RAS(ON) inhibitor daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. Full phase 3 RASolute 302 trial results: https://t.co/xwLWBZYRzq

@ASCO

[Louisa Nicola @louisanicola_]

Alzheimer’s disease does not begin with memory loss.
It begins when your episodic memory network loses its ability to deactivate under load, driven by amyloid and tau disrupting synaptic signaling, which means your cognitive precision starts degrading years before you notice it. @NatureComms

[Shih-Feng You @SFYou614]

Top medical journal posts a AI generated image as feature photo, it’s been three days and seems no one in @NEJM feel like to retract it. This showcases how much our academic and publication system paralyzed by AI.

[NEJM @NEJM]

An 87-year-old man presented with difficulty breathing after having inhaled thick smoke from a forest fire for several hours. Respiratory failure developed. On flexible bronchoscopy, black casts were seen in the airway. Read the full case details: https://t.co/voUCyxw7JM

[Marios Georgakis @MariosGeorgakis]

To understand most genetic signals for human disease that are located in non-coding regions, we will need to explore their effects on gene expression at the single-cell level.

Two new valuable resources apply this in brain tissue and neurological disease👇

[Stephen Quake @StephenQuake]

Aging isn't just a dimmer switch; it’s a logistics failure. In @NatureAging, Doug Henze, Tony Wyss-Coray, and I show how mRNA "gets stuck" in aging microglia, causing degradation of their spatial context: https://t.co/HFv4MNDiBA

[John Lukens @LukensJohnR]

Distinct origins and niches determine the cellular responsiveness of CNS macrophages after repopulation
https://t.co/NfjMGx0GRE

[Xin Jin, PhD @xinjin]

📢 Preprint: we present a whole-mouse-brain in vivo Perturb-seq atlas, 7.7 million cells, 1947 disease-associated perturbations, moving toward direct readout of how human genetics rewires cell states & circuits in vivo. Grateful for the Team! @NVIDIAHealth https://t.co/01c1KFuLFw

[Dr. Alex Wissner-Gross @alexwg]

https://t.co/N2AwpI9f8m

[Chew Wei Leong @ChewWeiLeong]

Spatial perturb-seq: single-cell functional genomics within intact tissue architecture

Scale up your in situ CRISPR screens

Out in @NatureComms

[Tom Dörr @tom_doerr]

Bioinformatics research assistant on WhatsApp

https://t.co/QB8Dx0N4Ts

[Stephen Turner 🦋 @stephenturner.us @strnr]

geneSTRUCTURE: A Modern Platform for Visualization of Gene Structures https://t.co/bJ969VXXy8 🧬💻🧪 https://t.co/5BTi3grAwo

[Sanbu ��步 @sanbuphy]

做生物、医学的朋友可以关注这个 skills：OpenClaw Medical Skills 震惊到，872个医学AI agent技能集全，从临床到生信、药物发现、医疗器械、健康管理一应俱全。
是时候让你的🦞学会医疗技巧了，一个🦞就是一个生物学信息医学信息专家： https://t.co/krQC2zWMEY

[Hao Yin @HaoYin20]

#SpatialTranscriptomics

Optimizing Xenium @10xGenomics In Situ data utility by quality assessment & best-practice analysis workflows

If you are a Xenium user, this is a must-read🔥

👉Segmentation: Cellpose + Baysor (Segmentation-free alternative: SSAM, Points2Regions)
👉Preprocessing: Library size normalization, log-transformation, scaling, k-nearest neighbors graph (all PCs + 16 neighbors), Louvain clustering
👉Spatially variable feature selection: Squidpy Moran's I, Seurat Moran's I, Sinfonia, SomDE, Giotto, Hotspot
👉Imputation: SpaGE, Seurat, Tangram, SpaOTsc
👉Spatial domain identification: binning-based strategy, Bansky, SPACEL

Performance
vs CosMX, Molecular cartography, MERFISH, MERSCOPE, high-sensitivity ISS

@naturemethods 2025
https://t.co/blSirtI7rG

[Ruslan Rust @rust_ruslan]

PlotGDP: an AI Agent for Bioinformatics Plotting

https://t.co/qHwasBWiVf

[William Lagakos @caloriesproper2]

A mouse circadian proteome atlas - it's a monster https://t.co/opQ7L54C3t

[Alzforum @alzforum]

PET tracers specific for activated and homeostatic microglia are in the works. One targets TREM2, the other P2Y12R. #alzheimersdisease @LMU_Muenchen https://t.co/bQnKplcDyE

[John Lukens @LukensJohnR]

Clonal CD8+ T cells populate the leptomeninges and coordinate with immune cells in human degenerative brain diseases
https://t.co/VUQTqrWcnn

[Shih-Feng You @SFYou614]

@mvankerkhove @HHS_Jim @WHO As an epidemiologist, when you read in the email, “the cases have been isolated for treatment” and your conclusion is “they just here asking foe information”?

Where you got your training?

[Dr. Dominic Ng @DrDominicNg]

Cancer patients rarely get Alzheimer's.

And a 15-year study in @Cell just explained why. They found a protein that clears brain plaques in mice - by activating the brain's own IMMUNE CELLS 🧵

[Alzforum @alzforum]

A large study claims that in addition to ApoE4, ApoE3 is an Alzheimer’s risk allele, too. Without both of them, AD would be rare. https://t.co/iopUsuV8AK