Stochastic force inference via density estimation (2310.02366v1)
Abstract: Inferring dynamical models from low-resolution temporal data continues to be a significant challenge in biophysics, especially within transcriptomics, where separating molecular programs from noise remains an important open problem. We explore a common scenario in which we have access to an adequate amount of cross-sectional samples at a few time-points, and assume that our samples are generated from a latent diffusion process. We propose an approach that relies on the probability flow associated with an underlying diffusion process to infer an autonomous, nonlinear force field interpolating between the distributions. Given a prior on the noise model, we employ score-matching to differentiate the force field from the intrinsic noise. Using relevant biophysical examples, we demonstrate that our approach can extract non-conservative forces from non-stationary data, that it learns equilibrium dynamics when applied to steady-state data, and that it can do so with both additive and multiplicative noise models.
- (2022) Interpretable and tractable models of transcriptional noise for the rational design of single-molecule quantification experiments. Nature Communications 13:7620.
- Thattai M, van Oudenaarden A (2001) Intrinsic noise in gene regulatory networks. Proceedings of the National Academy of Sciences 98:8614–8619 Publisher: Proceedings of the National Academy of Sciences.
- Losick R, Desplan C (2008) Stochasticity and Cell Fate. Science 320:65–68 Publisher: American Association for the Advancement of Science.
- Bialek W, et al. (2012) Statistical mechanics for natural flocks of birds. Proceedings of the National Academy of Sciences 109:4786–4791.
- Grilli J (2020) Macroecological laws describe variation and diversity in microbial communities. Nature Communications 11:4743.
- Gardiner C (2009) Stochastic Methods, 0172-7389 (Springer-Verlag Berlin Heidelberg) Vol. 13.
- (2018) High-performance reconstruction of microscopic force fields from Brownian trajectories. Nature Communications 9:5166.
- Frishman A, Ronceray P (2020) Learning Force Fields from Stochastic Trajectories. Physical Review X 10:021009.
- (2020) Building General Langevin Models from Discrete Datasets. Physical Review X 10:031018.
- Kutoyants YA (2004) Statistical Inference for Ergodic Diffusion Processes, Springer Series in Statistics (Springer, London).
- Yang KD, Uhler C (2018) Scalable unbalanced optimal transport using generative adversarial networks. arXiv preprint arXiv:1810.11447.
- Schiebinger G, et al. (2019) Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming. Cell 176:928–943.e22.
- Schiebinger G (2021) Reconstructing developmental landscapes and trajectories from single-cell data. Current Opinion in Systems Biology 27:100351.
- (2021) Optimal transport analysis reveals trajectories in steady-state systems. PLOS Computational Biology 17:e1009466 Publisher: Public Library of Science.
- Yang KD, et al. (2020) Predicting cell lineages using autoencoders and optimal transport. PLOS Computational Biology 16:e1007828 Publisher: Public Library of Science.
- Bunne C, et al. (2021) Learning Single-Cell Perturbation Responses using Neural Optimal Transport. Pages: 2021.12.15.472775 Section: New Results.
- (2020) Trajectorynet: A dynamic optimal transport network for modeling cellular dynamics (PMLR), pp 9526–9536.
- (2022) Trajectory Inference via Mean-field Langevin in Path Space.
- (2023) Towards a mathematical theory of trajectory inference.
- (2023) The Schrodinger Bridge between Gaussian Measures has a Closed Form. arXiv:2202.05722 [cs, q-bio] version: 2.
- (2022) Noise distorts the epigenetic landscape and shapes cell-fate decisions. Cell Systems 13:83–102.e6.
- (2018) Broken detailed balance and non-equilibrium dynamics in living systems: a review. Reports on Progress in Physics 81:066601 Publisher: IOP Publishing.
- (2022) Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology 31:100435.
- Hyvärinen A (2005) Estimation of Non-Normalized Statistical Models by Score Matching. Journal of Machine Learning Research 6:695–709.
- Roldán É, Parrondo JMR (2010) Estimating Dissipation from Single Stationary Trajectories. Physical Review Letters 105:150607.
- (2019) Inferring broken detailed balance in the absence of observable currents. Nature Communications 10:3542.
- (2018) Fundamental limits on dynamic inference from single-cell snapshots. Proceedings of the National Academy of Sciences 115:E2467–E2476 Publisher: Proceedings of the National Academy of Sciences.
- (2016) Learning Population-Level Diffusions with Generative RNNs (PMLR), pp 2417–2426 ISSN: 1938-7228.
- (2020) Interacting Particle Solutions of Fokker–Planck Equations Through Gradient–Log–Density Estimation. Entropy 22:802.
- Song Y, et al. (2020) Score-Based Generative Modeling through Stochastic Differential Equations.
- (2020) Sliced Score Matching: A Scalable Approach to Density and Score Estimation (PMLR), pp 574–584.
- (2022) Inverse dirichlet weighting enables reliable training of physics informed neural networks. Machine Learning: Science and Technology 3:015026.
- (2006) A kernel method for the two-sample-problem. Advances in neural information processing systems 19.
- (2018) Learning Generative Models with Sinkhorn Divergences (PMLR), pp 1608–1617.
- (2020) Implicit neural representations with periodic activation functions. Advances in neural information processing systems 33:7462–7473.
- (1984) Bistable systems: Master equation versus Fokker-Planck modeling. Physical Review A 29:371–378 Publisher: American Physical Society.
- (2011) GeneNetWeaver: in silico benchmark generation and performance profiling of network inference methods. Bioinformatics 27:2263–2270.
- (2020) Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data. Nature Methods 17:147–154.