Paper List
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Developing the PsyCogMetrics™ AI Lab to Evaluate Large Language Models and Advance Cognitive Science
This paper addresses the critical gap between sophisticated LLM evaluation needs and the lack of accessible, scientifically rigorous platforms that in...
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Equivalence of approximation by networks of single- and multi-spike neurons
This paper resolves the fundamental question of whether single-spike spiking neural networks (SNNs) are inherently less expressive than multi-spike SN...
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The neuroscience of transformers
提出了Transformer架构与皮层柱微环路之间的新颖计算映射,连接了现代AI与神经科学。
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Framing local structural identifiability and observability in terms of parameter-state symmetries
This paper addresses the core challenge of systematically determining which parameters and states in a mechanistic ODE model can be uniquely inferred ...
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Leveraging Phytolith Research using Artificial Intelligence
This paper addresses the critical bottleneck in phytolith research by automating the labor-intensive manual microscopy process through a multimodal AI...
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Neural network-based encoding in free-viewing fMRI with gaze-aware models
This paper addresses the core challenge of building computationally efficient and ecologically valid brain encoding models for naturalistic vision by ...
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Scalable DNA Ternary Full Adder Enabled by a Competitive Blocking Circuit
This paper addresses the core bottleneck of carry information attenuation and limited computational scale in DNA binary adders by introducing a scalab...
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ELISA: An Interpretable Hybrid Generative AI Agent for Expression-Grounded Discovery in Single-Cell Genomics
This paper addresses the critical bottleneck of translating high-dimensional single-cell transcriptomic data into interpretable biological hypotheses ...
Ill-Conditioning in Dictionary-Based Dynamic-Equation Learning: A Systems Biology Case Study
Northwestern University | NSF-Simons National Institute for Theory and Mathematics in Biology
30秒速读
IN SHORT: This paper addresses the critical challenge of numerical ill-conditioning and multicollinearity in library-based sparse regression methods (e.g., SINDy), which leads to unstable and inaccurate recovery of governing equations from biological time-series data.
核心创新
- Methodology Quantitatively demonstrates that severe ill-conditioning (condition numbers up to 10^18) arises even with simple 2-3 term combinations in polynomial libraries, fundamentally limiting sparse identification methods.
- Methodology Shows that orthogonal polynomial bases (e.g., Legendre, Chebyshev) fail to improve conditioning when data distributions deviate from their theoretical weight functions, sometimes performing worse than monomials.
- Methodology Proposes and validates that aligning the data sampling distribution with the orthogonal basis's weight function can mitigate ill-conditioning and improve model recovery accuracy.
主要结论
- Ill-conditioning is pervasive in polynomial libraries for biological systems: condition numbers reach O(10^5) for Lotka-Volterra and O(10^18) for chemical reaction network models, leading to systematic model misidentification.
- Orthogonal polynomial bases are not a universal solution; they can worsen conditioning when data distributions (e.g., from constrained biological trajectories) deviate from the basis's required weight function.
- Distribution-aligned sampling is a key enabler: when data are sampled according to the orthogonal basis's weight function, conditioning improves significantly, enabling more accurate equation recovery.
摘要: Data-driven discovery of governing equations from time-series data provides a powerful framework for understanding complex biological systems. Library-based approaches that use sparse regression over candidate functions have shown considerable promise, but they face a critical challenge when candidate functions become strongly correlated: numerical ill-conditioning. Poor or restricted sampling, together with particular choices of candidate libraries, can produce strong multicollinearity and numerical instability. In such cases, measurement noise may lead to widely different recovered models, obscuring the true underlying dynamics and hindering accurate system identification. Although sparse regularization promotes parsimonious solutions and can partially mitigate conditioning issues, strong correlations may persist, regularization may bias the recovered models, and the regression problem may remain highly sensitive to small perturbations in the data. We present a systematic analysis of how ill-conditioning affects sparse identification of biological dynamics using benchmark models from systems biology. We show that combinations involving as few as two or three terms can already exhibit strong multicollinearity and extremely large condition numbers. We further show that orthogonal polynomial bases do not consistently resolve ill-conditioning and can perform worse than monomial libraries when the data distribution deviates from the weight function associated with the orthogonal basis. Finally, we demonstrate that when data are sampled from distributions aligned with the appropriate weight functions corresponding to the orthogonal basis, numerical conditioning improves, and orthogonal polynomial bases can yield improved model recovery accuracy across two baseline models. Relevance to Life Sciences Numerical ill-conditioning is especially consequential in the model discovery for biological systems, where nonlinear interactions are often represented using nonlinear functions such as polynomials, and where multiscale dynamics, constrained state trajectories, and limited sampling due to experimental limitations can further amplify multicollinearity. We demonstrate these effects across benchmark models relevant to metabolic networks, regulatory networks, and population dynamics. Our results show that poor conditioning can impair the recovery of biologically meaningful governing equations, while sampling strategies matched to the candidate basis can improve identification accuracy. These results imply that a broader range of dynamic sampling is needed in most biological experiments to produce data sets that are suitable for data-driven model discovery with current methods. Mathematical Content This paper studies sparse regression-based equation discovery in the presence of multicollinearity and numerical ill-conditioning. We analyze the conditioning of candidate libraries, especially monomial and orthogonal polynomial bases, using condition numbers and model recovery under realistic sampling conditions with publicly available experimental data. We compare how basis choice and sampling distribution affect regression stability, sparsity, and the accuracy of recovered dynamical models.