Will Macnair

Thank you Alzforum for featuring our new preprint identifying regulators of disease states of #microglia.

Project led by Amanda McQuade, computation by Reet Mishra, collaboration with the Nunez and De Jager labs.

Alzforum
www.alzforum.org/news/researc...

Preprint
www.biorxiv.org/content/10.1...

Figure 1 showing the strategy to isolate nuclei from the brain including blood vessels and the epigenetic profiles of 6 major brain cell types.

Happy to share our latest work led by @kevincziegler.bsky.social and Aydan Askarova, examining cell type contributions of vascular cell types to dementia risk. Many thanks to the donors, and for support from @ukdri.ac.uk and @alzassociation.bsky.social.
www.cell.com/neuron/fullt...

Impact of Alzheimer's disease risk factors and local neuromelanin content on the transcriptomic landscape of the human locus coeruleus The locus coeruleus (LC) is a small noradrenergic nucleus in the dorsal pons that sends projections across the brain regulating sleep, arousal, attention, stress responses, and some forms of cognition...

Got with the times + made a BSky to share our new, large-scale spatial RNAseq study of adult human #locuscoeruleus! Co-1st auth and cryostat wizard @heenadivecha.bsky.social squeezed 85 tissue sections into 43 Visium arrays. (1/8)

www.biorxiv.org/content/10.1...

A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences The spinal cord is the gateway for sensory information from the body as it ascends to the brain, as well as a major motor output center of the nervous system. It is also a key location for sensory-mot...

Thrilled to share our latest preprint using single nuq sequencing and Xenium to define neuron organisation and sex differences in glia within human spinal cord. Truly a collaborative effort, with a big shoutout to Katherin Gabriel and @tedpricethepainguy.bsky.social

www.biorxiv.org/content/10.1...

Excited to share our newest project using spatial transcriptomics with novel image analysis approaches to investigate the impact of biological risk factors for Alzheimer's disease (AD) - APOE haplotype, sex, and genomic ancestry - on molecular states in the locus coeruleus (LC 🔵) of the human 🧠.

Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementia #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.10.20.25338060v1

APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons #NeuroDegeneration 🧪🧠
https://www.biorxiv.org/content/10.1101/2025.10.24.684364v1

Furthermore I am more convinced that the real AI breakthrough is the attention concept (attention being all you need from the famous paper) - the ability to do data-driven model discovery. LLMs are just one place where this attention scheme is powerful. There are many more.

Deep Learning-Based Genetic Perturbation Models Do Outperform Uninformative Baselines on Well-Calibrated Metrics #SingleCell 🧪🧬🖥️
https://www.biorxiv.org/content/10.1101/2025.10.20.683304v1

Always take sentences using “the Cloud” or “the Internet” and try replacing those phrases with “A shed in Virginia” to see how they hold up. “Our service is fully based in a shed in Virginia”; “All my files are in a shed in Virginia”; “A shed in Virginia was designed to survive a nuclear war”, etc.

Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis - Nature Medicine Myelin damage in multiple sclerosis can be detected up to 7 years before symptoms, with early immune pathway activation and a 21-protein panel showing promise for presymptomatic diagnosis.

Several years before onset of symptoms of multiple sclerosis, there is evidence of central nervous system myelin injury
nature.com/articles/s41...

Four-panel chart grid: a) scatter plot of mpg vs. wt; b) box plot of mpg vs. cyl; c) line plot of mpg vs. disp; and d) bar chart of carb count.

Announcing Plotnine 0.15.0: The Python package for Grammar of Graphics gets a massive upgrade!

A new feature is Native Plot Composition: combine multiple independent plots into one figure, no more layout managers for multi-panel #Python graphs!

Read the post: posit.co/blog/plotnin...

Super useful new feature! I've started to recommend plotnine to everybody who does data analysis in python and needs a plotting solution, so this is very welcome.

For Twitter refugees:
A science and an #NIH starter pack.

First, my neuro starter pack. 1/

BIG ANNOUNCEMENT📣: I haven’t been this excited to be part of something new in 15 years… Thrilled to reveal the passion project I’ve been working on for the past year and a half!🙀🥳 (thread 👇)

A single-cell genetic colocalization test improves power and resolves disease-mediating cell types #SingleCell 🧪🧬🖥️
https://www.biorxiv.org/content/10.1101/2025.10.10.681685v1

Multi-scale integration of human brain vasculature and CSF proteomes reveals biomarkers of cerebral amyloid angiopathy linked to Alzheimer's disease risk #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.10.08.25337413v1

Long-read genome sequencing and multi-omics in aging and neurodegeneration #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.10.10.25337775v1

Distinct Filament Conformation for Receptor-Bound Amyloid-β from Alzheimers Disease Brain #NeuroDegeneration 🧪🧠
https://www.biorxiv.org/content/10.1101/2025.10.10.681740v1

Brain wide engraftment of human monocytes induces neurodegeneration and cognitive dysfunction #NeuroDegeneration 🧪🧠
https://www.researchsquare.com/article/rs-7762816/latest

Connecting HTT intermediate alleles and microRNA dysregulation to enhanced tauopathy in Late-Onset Alzheimer's Disease #NeuroDegeneration 🧪🧠
https://www.researchsquare.com/article/rs-7621820/latest

IPSC-based modeling of resiliency in centenarians reveals longevity-specific signatures #NeuroDegeneration 🧪🧠
https://www.biorxiv.org/content/10.1101/2025.10.10.681757v1

Staff Scientist About EMBL-EBI EMBL’s European Bioinformatics Institute is a data powerhouse, utilised on a global scale to advance scientific discovery through bioinformatics and solutions to some of the world’s mos...

I am hiring! - looking for a Staff Scientist to co-run my research group with me. Staff Scientist is a senior professional scientist role at EMBL. Please forward to people you might know who could be interested! embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

And it's posted! If you're interested and eligible, please consider applying through the UMD portal: umd.wd1.myworkdayjobs.com/en-US/UMCP/j....

If you're a PI working in algorithmic genomics (& you can recommend my lab to your top graduating students ;P), please let them know!

Beyond amyloid and tau: synaptic and neurodegenerative biomarkers shape MCI progression #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.10.06.25337445v1

Aquaporin-4 polymorphisms modify the penetrance of Parkinson's disease in leucine-rich repeat kinase 2 carriers #NeuroDegeneration 🧪🧠
http://medrxiv.org/cgi/content/short/2025.10.04.25337325v1

Optimal Gene Panel Selection for Targeted Spatial Transcriptomics Experiments #SingleCell 🧪🧬🖥️
https://www.biorxiv.org/content/10.1101/2025.10.08.681071v1

Finding the perfect promoter: Correlating single-cell transcriptome data with gene drive performance #SingleCell 🧪🧬🖥️
https://www.biorxiv.org/content/10.1101/2025.10.08.681126v1

1) We’ve written an article about the DecodeME results: what the study measured, what the results show, and why its findings are important.

Integrative multiomic analysis links TDP-43-driven splicing defects to cascading proteomic disruption of ALS/FTD pathways #NeuroDegeneration 🧪🧠
https://www.biorxiv.org/content/10.1101/2025.09.29.679403v1