Paper List
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EnzyCLIP: A Cross-Attention Dual Encoder Framework with Contrastive Learning for Predicting Enzyme Kinetic Constants
This paper addresses the core challenge of jointly predicting enzyme kinetic parameters (Kcat and Km) by modeling dynamic enzyme-substrate interaction...
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Tissue stress measurements with Bayesian Inversion Stress Microscopy
This paper addresses the core challenge of measuring absolute, tissue-scale mechanical stress without making assumptions about tissue rheology, which ...
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DeepFRI Demystified: Interpretability vs. Accuracy in AI Protein Function Prediction
This study addresses the critical gap between high predictive accuracy and biological interpretability in DeepFRI, revealing that the model often prio...
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Hierarchical Molecular Language Models (HMLMs)
This paper addresses the core challenge of accurately modeling context-dependent signaling, pathway cross-talk, and temporal dynamics across multiple ...
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Stability analysis of action potential generation using Markov models of voltage‑gated sodium channel isoforms
This work addresses the challenge of systematically characterizing how the high-dimensional parameter space of Markov models for different sodium chan...
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Personalized optimization of pediatric HD-tDCS for dose consistency and target engagement
This paper addresses the critical limitation of one-size-fits-all HD-tDCS protocols in pediatric populations by developing a personalized optimization...
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Consistent Synthetic Sequences Unlock Structural Diversity in Fully Atomistic De Novo Protein Design
This paper addresses the core pain point of low sequence-structure alignment in existing synthetic datasets (e.g., AFDB), which severely limits the pe...
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Generative design and validation of therapeutic peptides for glioblastoma based on a potential target ATP5A
This paper addresses the critical bottleneck in therapeutic peptide design: how to efficiently optimize lead peptides with geometric constraints while...
Setting up for failure: automatic discovery of the neural mechanisms of cognitive errors
Department of Engineering, University of Cambridge | Department of Psychology, University of Cambridge | Department of Cognitive Science, Central European University
The 30-Second View
IN SHORT: This paper addresses the core challenge of automating the discovery of biologically plausible recurrent neural network (RNN) dynamics that can replicate the full richness of human and animal behavioral data, including characteristic errors and suboptimalities, rather than just optimal task performance.
Innovation (TL;DR)
- Methodology Introduces a novel diffusion model-based training objective for RNNs to capture complex, multimodal behavioral response distributions (e.g., from swap errors), moving beyond traditional moment-matching or simple loss functions like MSE.
- Methodology Proposes using a non-parametric generative model (Bayesian Non-parametric model of Swap errors, BNS) to create surrogate behavioral data for training, overcoming the data scarcity problem inherent in experimental neuroscience.
- Biology Demonstrates that RNNs trained to reproduce suboptimal behavior (swap errors) successfully recapitulate qualitative neural signatures (e.g., planar alignment of population activity) observed in macaque prefrontal cortex during visual working memory tasks, which task-optimal networks fail to capture.
Key conclusions
- RNNs trained with the novel diffusion-based method to reproduce probe-distance-dependent swap errors successfully matched the planar alignment geometry of neural population activity observed in macaque PFC (cosine similarity increase during cue period, as in Panichello et al., 2021), a signature not captured by task-optimal or no-swap-error models.
- The method accurately replicated target swap error rates as a function of distractor proximity (as defined by the generative BNS model), demonstrating quantitative fitting to complex behavioral distributions.
- The approach generated novel, testable hypotheses about the neural circuit mechanisms underlying swap errors (e.g., misselection at cue time), moving beyond descriptive population coding models.
Abstract: Discovering the neural mechanisms underpinning cognition is one of the grand challenges of neuroscience. However, previous approaches for building models of recurrent neural network (RNN) dynamics that explain behaviour required iterative refinement of architectures and/or optimization objectives, resulting in a piecemeal, and mostly heuristic, human-in-the-loop process. Here, we offer an alternative approach that automates the discovery of viable RNN mechanisms by explicitly training RNNs to reproduce behaviour, including the same characteristic errors and suboptimalities, that humans and animals produce in a cognitive task. Achieving this required two main innovations. First, as the amount of behavioural data that can be collected in experiments is often too limited to train RNNs, we use a non-parametric generative model of behavioural responses to produce surrogate data for training RNNs. Second, to capture all relevant statistical aspects of the data, rather than a limited number of hand-picked low-order moments as in previous moment-matching-based approaches, we developed a novel diffusion model-based approach for training RNNs. To showcase the potential of our approach, we chose a visual working memory task as our test-bed, as behaviour in this task is well known to produce response distributions that are patently multimodal (due to so-called swap errors). The resulting network dynamics correctly predicted previously reported qualitative features of neural data recorded in macaques. Importantly, these results were not possible to obtain with more traditional approaches, i.e., when only a limited set of behavioural signatures (rather than the full richness of behavioural response distributions) were fitted, or when RNNs were trained for task optimality (instead of reproducing behaviour). Our approach also yields novel predictions about the mechanism of swap errors, which can be readily tested in experiments. These results suggest that fitting RNNs to rich patterns of behaviour provides a powerful way to automatically discover the neural network dynamics supporting important cognitive functions.