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[10/10] Finally, thanks to all our best collaborators: Bart Smets, Rowan Saloner, Shinya Tasaki, Ying Xu, Varsha Krish, Farhad Imam, Danielle van Westen, Christopher D. Whelan!

[9/10] And massive thanks to the coolest ‪@biofinder.bsky.social‬ team—Shorena Janelidze, Erik Stomrud, Sebastian Palmqvist, ‪@rikossenkoppele.bsky.social‬, Niklas Mattsson-Carlgren, and Oskar Hansson —for sharing the awesome data and supporting this project every step of the way.

[8/10] Endless thanks to ‪@jwvogel.bsky.social‬ for guiding and supporting this work from day one. To our amazing team, especially Alexa Pichet Binette, Ines Hristovska, Gabriele Vilkaite, and @xiaoyucaly.bsky.social‬, for their enormous support.

[7/10] ProtAIDe-Dx is a step toward the development of scalable, minimally invasive, and multi-disease diagnostic tools for neurodegenerative diseases. We hope our work can establish a benchmark for AI-driven proteomics tools, paving the way for precision medicine in these diseases.

[6/10] We built a proof-of-concept diagnostic report with ProtAIDe-Dx, visualizing diagnostic probabilities across conditions and highlighting proteins that contributed to the individual’s prediction and traits linked to those proteins, enabling a biologically interpretable diagnosis.[Figure 5]

[5/10] Could ProtAIDe-Dx aid real-world clinical application? In a memory clinic cohort, ProtAIDe-Dx significantly improved differential diagnosis (especially PD and CVD) when combined with accessible clinical biomarkers (MMSE, MRI, plasma p-tau217 & NfL). (Figure 4D).

[4/10] ProtAIDe-Dx identified a novel and compact set of top predictive proteins. Notably, OMG and Histone H1-2 (H1-2) distinguished controls from all neurodegenerative conditions, and ubiquitin (UBB) was a discriminative protein for FTD. [Figure 3A].

[3/10] The models’ diagnostic probabilities highlighted subgroups of patients with proteomic patterns more similar to a different condition, e.g., AD patients resembling stroke patients, indicating possible misdiagnosis, potential co-pathology, or may even indicate distinct etiologies. [Figure 2A].

[2/10] We developed a multi-task model, ProtAIDe-Dx, to provide simultaneous probabilistic diagnosis across six conditions associated with dementia in aging (Control, AD, PD, FTD, ALS, and Stroke/TIA). CVed balanced ranged from 69%-96% and AUCs > 79% across all conditions. [Figure 1B]

[1/10] For the first time, we can answer this question with the world's largest neurodegeneration proteomics consortium, GNPC @neuroproteome.bsky.social #GNPC #Neurodegeneration #Proteomics #OpenScience #ADRD #Biomarkers #Parkinsons #ALS #FTD #NatureMedicine #NatureAging #SomaScan #Plasma #CSF

🧵15/ Huge thanks to our amazing team and coauthors!

Endless thanks to @jwvogel.bsky.social for guiding and supporting this work from day one. To our amazing team DeMON lab, especially @anlijuncn.bsky.social for enormous support.