Paper List
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Pharmacophore-based design by learning on voxel grids
This paper addresses the computational bottleneck and limited novelty in conventional pharmacophore-based virtual screening by introducing a voxel cap...
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CONFIDE: Hallucination Assessment for Reliable Biomolecular Structure Prediction and Design
This paper addresses the critical limitation of current protein structure prediction models (like AlphaFold3) where high-confidence scores (pLDDT) can...
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On the Approximation of Phylogenetic Distance Functions by Artificial Neural Networks
This paper addresses the core challenge of developing computationally efficient and scalable neural network architectures that can learn accurate phyl...
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EcoCast: A Spatio-Temporal Model for Continual Biodiversity and Climate Risk Forecasting
This paper addresses the critical bottleneck in conservation: the lack of timely, high-resolution, near-term forecasts of species distribution shifts ...
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Training Dynamics of Learning 3D-Rotational Equivariance
This work addresses the core dilemma of whether to use computationally expensive equivariant architectures or faster symmetry-agnostic models with dat...
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Fast and Accurate Node-Age Estimation Under Fossil Calibration Uncertainty Using the Adjusted Pairwise Likelihood
This paper addresses the dual challenge of computational inefficiency and sensitivity to fossil calibration errors in Bayesian divergence time estimat...
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Few-shot Protein Fitness Prediction via In-context Learning and Test-time Training
This paper addresses the core challenge of accurately predicting protein fitness with only a handful of experimental observations, where data collecti...
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scCluBench: Comprehensive Benchmarking of Clustering Algorithms for Single-Cell RNA Sequencing
This paper addresses the critical gap of fragmented and non-standardized benchmarking in single-cell RNA-seq clustering, which hinders objective compa...
Stability analysis of action potential generation using Markov models of voltage‑gated sodium channel isoforms
School of Mathematics and Statistics, Rochester Institute of Technology | School of Physics, Rochester Institute of Technology | School of Physics and Astronomy & School of Mathematics and Statistics, Rochester Institute of Technology
The 30-Second View
IN SHORT: This work addresses the challenge of systematically characterizing how the high-dimensional parameter space of Markov models for different sodium channel isoforms influences the robustness and excitability of neuronal firing.
Innovation (TL;DR)
- Methodology Integrates a six-state Markov model for nine human NaV isoforms with a simplified KV3.1 model, enabling a unified framework for isoform-specific stability analysis.
- Methodology Applies bifurcation theory and local stability analysis to map 'excitable landscapes' across the (g_Na, g_K) parameter space, visualizing regions supporting stable oscillatory behavior.
- Biology Quantitatively ranks NaV isoforms by their supported excitable regimes, identifying NaV1.3, 1.4, and 1.6 as broadly supportive and NaV1.7 and 1.9 as minimally oscillatory.
Key conclusions
- Isoforms NaV1.3, NaV1.4, and NaV1.6 support the broadest parameter regions for stable limit cycles (oscillatory firing), indicating their robustness in sustaining action potential trains.
- Isoforms NaV1.7 and NaV1.9 exhibit minimal oscillatory behavior across the tested conductance parameter space, correlating with their specialized roles in peripheral nociception.
- The hybrid Markov-HH modeling and stability analysis framework successfully narrows the vast parameter search space for designing synthetic excitable systems, moving from trial-and-error to principled design.
Abstract: We investigate a conductance‑based neuron model to explore how voltage‑gated ion channel isoforms influence action‑potential generation. The model combines a six‑state Markov representation of NaV channels with a first‑order KV3.1 model, allowing us to vary maximal sodium and potassium conductances and compare nine NaV isoforms. Using bifurcation theory and local stability analysis, we map regions of stable limit cycles and visualize excitability landscapes via heatmap‑based diagrams. These analyses show that isoforms NaV1.3, NaV1.4 and NaV1.6 support broad excitable regimes, while isoforms NaV1.7 and NaV1.9 exhibit minimal oscillatory behavior. Our findings provide insights into the role of channel heterogeneity in neuronal dynamics and may help to guide the design of synthetic excitable systems by narrowing the parameter space needed for robust action‑potential trains.