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Aden Forrow

Publications and source records attributed to Aden Forrow.

10 recordsLinked to original sources

Consistent diffusion matrix estimation from population time series

Progress on modern scientific questions regularly depends on using large-scale datasets to understand complex dynamical systems. An especially challenging case that has grown to prominence with advances in single-cell sequencing technologies is learning the behavior of individuals from population snapshots. In the absence of individual-level time series, standard stochastic differential equation models are often nonidentifiable because intrinsic diffusion cannot be distinguished from measurement noise. Despite the difficulty, accurately recovering diffusion terms is required to answer even basic questions about the system's behavior. We show how to combine population-level time series with velocity measurements to build a provably consistent estimator of the diffusion matrix.

q-bio.QM

Trajectory inference for a branching SDE model of cell differentiation

A core challenge for modern biology is how to infer the trajectories of individual cells from population-level time courses of high-dimensional gene expression data. Birth and death of cells present a particular difficulty: existing trajectory inference methods cannot distinguish variability in net proliferation from cell differentiation dynamics, and hence require accurate prior knowledge of the proliferation rate. Building on Global Waddington-OT (gWOT), which performs trajectory inference with rigorous theoretical guarantees when birth and death can be neglected, we show how to use lineage trees available with recently developed CRISPR-based measurement technologies to disentangle proliferation and differentiation. In particular, when there is neither death nor subsampling of cells, we show that we extend gWOT to the case with proliferation with similar theoretical guarantees and computational cost, without requiring any prior information. In the case of death and/or subsampling, our method introduces a bias, that we describe explicitly and argue to be inherent to these lineage tracing data. We demonstrate in both cases the ability of this method to reliably reconstruct the landscape of a branching SDE from time-courses of simulated datasets with lineage tracing, outperforming even a benchmark using the experimentally unavailable true branching rates.

q-bio.QM

Measuring the accuracy of likelihood-free inference

Complex scientific models where the likelihood cannot be evaluated present a challenge for statistical inference. Over the past two decades, a wide range of algorithms have been proposed for learning parameters in computationally feasible ways, often under the heading of approximate Bayesian computation or likelihood-free inference. There is, however, no consensus on how to rigorously evaluate the performance of these algorithms. Here, we argue for scoring algorithms by the mean squared error in estimating expectations of functions with respect to the posterior. We show that score implies common alternatives, including the acceptance rate and effective sample size, as limiting special cases. We then derive asymptotically optimal distributions for choosing or sampling discrete or continuous simulation parameters, respectively. Our recommendations differ significantly from guidelines based on alternative scores outside of their region of validity. As an application, we show sequential Monte Carlo in this context can be made more accurate with no new samples by accepting particles from all rounds.

stat.CO

Statistical Optimal Transport via Factored Couplings

We propose a new method to estimate Wasserstein distances and optimal transport plans between two probability distributions from samples in high dimension. Unlike plug-in rules that simply replace the true distributions by their empirical counterparts, our method promotes couplings with low transport rank, a new structural assumption that is similar to the nonnegative rank of a matrix. Regularizing based on this assumption leads to drastic improvements on high-dimensional data for various tasks, including domain adaptation in single-cell RNA sequencing data. These findings are supported by a theoretical analysis that indicates that the transport rank is key in overcoming the curse of dimensionality inherent to data-driven optimal transport.

stat.ML

Inverse Design of Discrete Mechanical Metamaterials

Mechanical and phononic metamaterials exhibiting negative elastic moduli, gapped vibrational spectra, or topologically protected modes enable precise control of structural and acoustic functionalities. While much progress has been made in their experimental and theoretical characterization, the inverse design of mechanical metamaterials with arbitrarily programmable spectral properties and mode localization remains an unsolved problem. Here, we present a flexible computational inverse-design framework that allows the efficient tuning of one or more gaps at nearly arbitrary positions in the spectrum of discrete phononic metamaterial structures. The underlying algorithm optimizes the linear response of elastic networks directly, is applicable to ordered and disordered structures, scales efficiently in 2D and 3D, and can be combined with a wide range of numerical optimization schemes. We illustrate the broad practical potential of this approach by designing mechanical bandgap switches that open and close pre-programmed spectral gaps in response to an externally applied stimulus such as shear or compression. We further show that the designed structures can host topologically protected edge modes, and validate the numerical predictions through explicit 3D finite element simulations of continuum elastica with experimentally relevant material parameters. Generally, this network-based inverse design paradigm offers a direct pathway towards manufacturing phononic metamaterials, DNA origami structures and topolectric circuits that can realize a wide range of static and dynamic target functionalities.

cond-mat.mtrl-sci

Functional control of network dynamics using designed Laplacian spectra

Complex real-world phenomena across a wide range of scales, from aviation and internet traffic to signal propagation in electronic and gene regulatory circuits, can be efficiently described through dynamic network models. In many such systems, the spectrum of the underlying graph Laplacian plays a key role in controlling the matter or information flow. Spectral graph theory has traditionally prioritized unweighted networks. Here, we introduce a complementary framework, providing a mathematically rigorous weighted graph construction that exactly realizes any desired spectrum. We illustrate the broad applicability of this approach by showing how designer spectra can be used to control the dynamics of various archetypal physical systems. Specifically, we demonstrate that a strategically placed gap induces chimera states in Kuramoto-type oscillator networks, completely suppresses pattern formation in a generic Swift-Hohenberg model, and leads to persistent localization in a discrete Gross-Pitaevskii quantum network. Our approach can be generalized to design continuous band gaps through periodic extensions of finite networks.

physics.soc-ph

Mode selection in compressible active flow networks

Coherent, large scale dynamics in many nonequilibrium physical, biological, or information transport networks are driven by small-scale local energy input. Here, we introduce and explore an analytically tractable nonlinear model for compressible active flow networks. In contrast to thermally-driven systems, we find that active friction selects discrete states with a limited number of oscillation modes activated at distinct fixed amplitudes. Using perturbation theory, we systematically predict the stationary states of noisy networks and find good agreement with a Bayesian state estimation based on a hidden Markov model applied to simulated time series data. Our results suggest that the macroscopic response of active network structures, from actomyosin force networks to cytoplasmic flows, can be dominated by a significantly reduced number of modes, in contrast to energy equipartition in thermal equilibrium. The model is also well-suited to study topological sound modes and spectral band gaps in active matter.

physics.bio-ph

Stochastic cycle selection in active flow networks

Active biological flow networks pervade nature and span a wide range of scales, from arterial blood vessels and bronchial mucus transport in humans to bacterial flow through porous media or plasmodial shuttle streaming in slime molds. Despite their ubiquity, little is known about the self-organization principles that govern flow statistics in such non-equilibrium networks. Here we connect concepts from lattice field theory, graph theory, and transition rate theory to understand how topology controls dynamics in a generic model for actively driven flow on a network. Our combined theoretical and numerical analysis identifies symmetry-based rules that make it possible to classify and predict the selection statistics of complex flow cycles from the network topology. The conceptual framework developed here is applicable to a broad class of non-biological far-from-equilibrium networks, including actively controlled information flows, and establishes a new correspondence between active flow networks and generalized ice-type models.

physics.bio-ph

Warning's Second Theorem with Resricted Variables

We present a restricted variable generalization of Warning's Second Theorem (a result giving a lower bound on the number of solutions of a low degree polynomial system over a finite field, assuming one solution exists). This is analogous to Brink's restricted variable generalization of Chevalley's Theorem (a result giving conditions for a low degree polynomial system not to have exactly one solution). Just as Warning's Second Theorem implies Chevalley's Theorem, our result implies Brink's Theorem. We include several combinatorial applications, enough to show that we have a general tool for obtaining quantitative refinements of combinatorial existence theorems.

math.NT

Variable Phase S-Matrix Calculations for Asymmetric Potentials and Dielectrics

Motivated by recently developed techniques making it possible to compute Casimir energies for any object whose scattering S-matrix (or, equivalently, T-matrix) is available, we develop a variable phase method to compute the S-matrix for localized but asymmetric sources. Starting from the case of scalar potential scattering, we develop a combined inward/outward integration algorithm that is numerically efficient and extends robustly to imaginary wave number. We then extend these results to electromagnetic scattering from a position-dependent dielectric. This case requires additional modifications to disentangle the transverse and longitudinal modes.

quant-ph