Paper List
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Nyxus: A Next Generation Image Feature Extraction Library for the Big Data and AI Era
This paper addresses the core pain point of efficiently extracting standardized, comparable features from massive (terabyte to petabyte-scale) biomedi...
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Topological Enhancement of Protein Kinetic Stability
This work addresses the long-standing puzzle of why knotted proteins exist by demonstrating that deep knots provide a functional advantage through enh...
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A Multi-Label Temporal Convolutional Framework for Transcription Factor Binding Characterization
This paper addresses the critical limitation of existing TF binding prediction methods that treat transcription factors as independent entities, faili...
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Social Distancing Equilibria in Games under Conventional SI Dynamics
This paper solves the core problem of proving the existence and uniqueness of Nash equilibria in finite-duration SI epidemic games, showing they are a...
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Binding Free Energies without Alchemy
This paper addresses the core bottleneck of computational expense in Absolute Binding Free Energy calculations by eliminating the need for numerous al...
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SHREC: A Spectral Embedding-Based Approach for Ab-Initio Reconstruction of Helical Molecules
This paper addresses the core bottleneck in cryo-EM helical reconstruction: eliminating the dependency on accurate initial symmetry parameter estimati...
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Budget-Sensitive Discovery Scoring: A Formally Verified Framework for Evaluating AI-Guided Scientific Selection
This paper addresses the critical gap in evaluating AI-guided scientific selection strategies under realistic budget constraints, where existing metri...
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Probabilistic Joint and Individual Variation Explained (ProJIVE) for Data Integration
This paper addresses the core challenge of accurately decomposing shared (joint) and dataset-specific (individual) sources of variation in multi-modal...
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.