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Reposted by Systems and Signals

Michele Frison @frisophagy.bsky.social · 10/10/2025

How can mitophagy be an effective quality control mechanism if mtDNA mutations reach high enough levels to cause disease? This question led us into a dark path, full of concepts of evolutionary genetics, germline stem cell biology and mito-nuclear compatibility. www.science.org/doi/10.1126/...

science.org

Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

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Reposted by Systems and Signals

Trevor Graham @trevorgraham.bsky.social · 10/09/2025

Studying cancer evolution needs multi-region or single cell seq for phylogenetics, right? Amazingly (I think!) we found single-sample bulk methylation suffices, via analysis of "fluctuating methylation". In @nature.com today led by brilliant @calumgabbutt.bsky.social www.nature.com/articles/s41...

nature.com

Fluctuating DNA methylation tracks cancer evolution at clinical scale - Nature

Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

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Systems and Signals @syssig.bsky.social · 29/08/2025

On SBMs, GCN + BRIDGE reaches about 99% on synthetic SBM graph benchmarks. On heterophilic real graphs we see consistent gains, e.g. Actor +4.8 pts, Chameleon +2.7 pts, while Cora, Citeseer, Pubmed stay near baseline. Code and docs: github.com/jr419/BRIDGE 8/8

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Systems and Signals @syssig.bsky.social · 29/08/2025

We prove the optimal structures for message passing are disjoint unions of single‑class clusters and two‑class bipartite clusters. This insight gives BRIDGE, a block‑resampling rewiring that uses predicted labels to sample an “optimal” graph. 7/8

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Systems and Signals @syssig.bsky.social · 29/08/2025

In SBMs we provide explicit asymptotic formulae of higher-order order homophily in terms of mean degree and expected edge homophily. Predicted SNR tracks accuracy on real graphs, and the node‑wise test flags where the graph helps before any training. 6/8

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Systems and Signals @syssig.bsky.social · 29/08/2025

This yields a local test that predicts when a GNN will beat a plain FNN. If same‑class nodes are poorly connected over multiple hops, message passing cannot lift SNR, no matter how you tune the model. 5/8

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Systems and Signals @syssig.bsky.social · 29/08/2025

The key limiter of SNR is class‑bottlenecks. We define a local class‑bottlenecking score and show that higher‑order homophily bounds signal sensitivity. 4/8

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Systems and Signals @syssig.bsky.social · 29/08/2025

We introduce a simple way to evaluate GNN performance using an SNR that splits into two parts: feature stats and feature‑agnostic sensitivities to class signal, local noise, and global shifts. 3/8

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Systems and Signals @syssig.bsky.social · 29/08/2025

The paper reveals precisely when, where and why graph neural networks struggle in node classification: We show it's not just about structural bottlenecks -- rather the interaction between structural bottlenecks and class labels, unifying heterophily & bottleneck literatures for the first time. 2/8

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Reposted by Systems and Signals

I-X @imperial-ix.bsky.social · 18/07/2025

🚀 AI in Science Fellowships – Applications Now Open! The I-X Centre for AI in Science is recruiting up to 19 fellows to join their prestigious programme and accelerate artificial intelligence research in Engineering, Natural and Mathematical Sciences. 1/5

lnkd.in

This link will take you to a page that’s not on LinkedIn

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Reposted by Systems and Signals

I-X @imperial-ix.bsky.social · 19/06/2025

🚨 Opening in mid-July: 🔹 Up to 8x 2-year Independent Fellowships in AI in Science, supported by @schmidtsciences.bsky.social 🔹 Up to 2x 2-year Joint Fellowships with ICR & CNRS 🔹 Up to 3x 1-year Linked Fellowships at Imperial (followed by a 1 year linked fellowship at AIMS and NCBS). 2/2

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Reposted by Systems and Signals

I-X @imperial-ix.bsky.social · 19/06/2025

🚨 AI in Science Fellowship Opportunities 🚨 🔹Now open: Up to 6x 4-year Independent Fellowships dedicated to AI in Science in a program supported by Schmidt Sciences and Imperial College London [@imperialcollegeldn.bsky.social]. 🔗 Find out more and apply: www.imperial.ac.uk/research-and... 1/2

imperial.ac.uk

Imperial College Research Fellowships | Research | Imperial College London

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Systems and Signals @syssig.bsky.social · 07/03/2025

Calorie restriction (CR) is known to improve healthy ageing and we find indications that CR rats have lowered levels of cryptic mtDNA mutations. CR can increase mtDNA numbers and our theory predicts that higher mtDNA copy-numbers slow accumulation of mtDNA mutations. 6/6

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Systems and Signals @syssig.bsky.social · 07/03/2025

Over 7 datasets, in multiple tissues in humans, mice and rats, cells with cryptic mtDNA mutations have gene expression changes consonant with ageing including immune effects and protein misfolding. We give experimental corroboration in human cell lines. 5/6

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Systems and Signals @syssig.bsky.social · 07/03/2025

The accumulation of mutations is nonlinear with a phase coinciding with mid-late life where mutations hit high levels. By late life ~a third of all cells have a mutation that has taken over the whole population. Our inferred mutation rate is consonant with literature values. 4/6

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Systems and Signals @syssig.bsky.social · 07/03/2025

We developed theory to account for the accumulation of these mutations and a hierarchical Bayesian inference framework to fit our models. We find that the accumulation of mutations conforms to our theory. We can predict an individual’s age from their levels of mutation. 3/6

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Systems and Signals @syssig.bsky.social · 07/03/2025

We find evidence that a mutation type, invisible in bulk, cryptic mtDNA mutation, makes up the majority of mtDNA mutations in aged post-mitotic tissues. Notably these mutations show weak evidence of negative selection despite many mtDNA mutations having physiological effects. 2/6

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Systems and Signals @syssig.bsky.social · 07/03/2025

We're pleased our exciting paper 'Cryptic mitochondrial ageing coincides with mid-late life and is pathophysiologically informative in single cells across tissues and species' is now out in Nature Comms: www.nature.com/articles/s41...

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Systems and Signals @syssig.bsky.social · 22/11/2024

Systems and signals group in Imperial maths led by Nick Jones. Stay tuned for our latest research on #mitochondria #aging #genetics #biomathematics #physicalbiology #networks and #ML. We blog at systems-signals.blogspot.com and there's more about us here profiles.imperial.ac.uk/nick.jones/a...

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