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Donor-Aware scRNA-seq Benchmarks for IBD Classification

arXiv.org Machine Learning

Donor-level disease classification from single-cell RNA sequencing (scRNA-seq) requires strict donor-aware cross-validation: naive pipelines that split cells randomly conflate training and test donors, inflating reported performance through pseudoreplication. We present a donor-aware benchmark evaluating three feature representations across two independent IBD cohorts: centered log-ratio (CLR) transformed cell-type composition, GatedStructuralCFN dependency embeddings, and scVI variational autoencoder latent embeddings. The cohorts are the SCP259 ulcerative colitis atlas (UC vs. Healthy, n=30 donors, 51 cell types) and the Kong 2023 Crohn's disease atlas (CD vs. Healthy, n=71 donors, 55-68 cell types across three intestinal regions). Compartment-stratified CLR composition achieves AUROC 0.956 +/- 0.061 on SCP259; GatedStructuralCFN on the same features achieves 0.978 +/- 0.050. In the Kong cohort, CFN achieves its best performance in the colon region (0.960 +/- 0.055 after feature filtering), exceeding linear CLR (0.900 +/- 0.100), while terminal ileum classification is dominated by linear models (CatBoost CLR 0.967 +/- 0.075 vs. CFN 0.811 +/- 0.164). Cross-dataset transfer (CD->UC, four shared cell types) achieves AUC 0.833 with XGBoost CLR; the reverse direction performs at chance. CFN edge stability analysis shows that compartment-wise composition eliminates spurious unit-sum-induced instability present in global composition (Jaccard 0.026 vs. top-20 recurrence 1.0). CFN shows a consistent numerical advantage over linear models in the colon region of CD (AUROC 0.960 vs. 0.900), though no inter-method comparison reached statistical significance at n<=34 donors per region. Compartment-aware feature construction is critical for both classification performance and structural interpretability. Code: https://github.com/Jonathan-321/sfn-scrna-study


5 Supplementary Material

Neural Information Processing Systems

Dendritic updates Complete versions of the dendritic update rules (summarised in Eqns (2) & (3)) are given below. This is valid in our regime where the environmental latent updates slowly compared to neural timescales. The notation we're using admits the possible presence of biases as well as the weights (though biases typically aren't used) by assuming a row of constant 1's could be added to the synaptic inputs effectively absorbing a bias into the weight matrix without loss of generality, for example wgB p(t) wgB p(t)+ bgB . Somatic updates Somatic updates rules (Eqns (4) & (5)) and are repeated here for completeness: p(t)= (t)pB(t)+(1 (t))pA(t) g(t)= (t)gB(t)+(1 (t))gA(t). Update ordering For this hierarchical network of multicompartmental neurons we must specify the order in which we perform these discrete updates to the different layers and the different compartments within these layers.


A generative model of the hippocampal formation trained with theta driven local learning rules

Neural Information Processing Systems

Advances in generative models have recently revolutionised machine learning. Meanwhile, in neuroscience, generative models have long been thought fundamental to animal intelligence. Understanding the biological mechanisms that support these processes promises to shed light on the relationship between biological and artificial intelligence. In animals, the hippocampal formation is thought to learn and use a generative model to support its role in spatial and non-spatial memory. Here we introduce a biologically plausible model of the hippocampal formation tantamount to a Helmholtz machine that we apply to a temporal stream of inputs. A novel component of our model is that fast theta-band oscillations (5-10 Hz) gate the direction of information flow throughout the network, training it akin to a high-frequency wake-sleep algorithm. Our model accurately infers the latent state of high-dimensional sensory environments and generates realistic sensory predictions. Furthermore, it can learn to path integrate by developing a ring attractor connectivity structure matching previous theoretical proposals and flexibly transfer this structure between environments.


How uncrewed narco subs could transform the Colombian drug trade

MIT Technology Review

Fast, stealthy, and cheap--autonomous, semisubmersible drone boats carrying tons of cocaine could be international law enforcement's nightmare scenario. A big one just came ashore. Colombian military officials intercepted this 40-foot-long uncrewed fiberglass "narco sub" in the ocean just off Tayrona National Park. On a bright morning last April, a surveillance plane operated by the Colombian military spotted a 40-foot-long shark-like silhouette idling in the ocean just off Tayrona National Park. It was, unmistakably, a "narco sub," a stealthy fiberglass vessel that sails with its hull almost entirely underwater, used by drug cartels to move cocaine north. The plane's crew radioed it in, and eventually nearby coast guard boats got the order, routine but urgent: Intercept. In Cartagena, about 150 miles from the action, Captain Jaime Gonzรกlez Zamudio, commander of the regional coast guard group, sat down at his desk to watch what happened next.


Scalable Bayesian inference of dendritic voltage via spatiotemporal recurrent state space models

Neural Information Processing Systems

Recent progress in the development of voltage indicators [1-8] has brought us closer to a longstanding goal incellular neuroscience: imaging the full spatiotemporal voltageonadendritic tree. These recordings have the potential (pun not intended) to resolve fundamental questions about the computations performed by dendrites -- questions that have remained open for more than a century[9,10].