Paper List
-
MCP-AI: Protocol-Driven Intelligence Framework for Autonomous Reasoning in Healthcare
This paper addresses the critical gap in healthcare AI systems that lack contextual reasoning, long-term state management, and verifiable workflows by...
-
Model Gateway: Model Management Platform for Model-Driven Drug Discovery
This paper addresses the critical bottleneck of fragmented, ad-hoc model management in pharmaceutical research by providing a centralized, scalable ML...
-
Tree Thinking in the Genomic Era: Unifying Models Across Cells, Populations, and Species
This paper addresses the fragmentation of tree-based inference methods across biological scales by identifying shared algorithmic principles and stati...
-
SSDLabeler: Realistic semi-synthetic data generation for multi-label artifact classification in EEG
This paper addresses the core challenge of training robust multi-label EEG artifact classifiers by overcoming the scarcity and limited diversity of ma...
-
Decoding Selective Auditory Attention to Musical Elements in Ecologically Valid Music Listening
This paper addresses the core challenge of objectively quantifying listeners' selective attention to specific musical components (e.g., vocals, drums,...
-
Physics-Guided Surrogate Modeling for Machine Learning–Driven DLD Design Optimization
This paper addresses the core bottleneck of translating microfluidic DLD devices from research prototypes to clinical applications by replacing weeks-...
-
Mechanistic Interpretability of Antibody Language Models Using SAEs
This work addresses the core challenge of achieving both interpretability and controllable generation in domain-specific protein language models, spec...
-
Fluctuating Environments Favor Extreme Dormancy Strategies and Penalize Intermediate Ones
This paper addresses the core challenge of determining how organisms should tune dormancy duration to match the temporal autocorrelation of their envi...
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.