arXiv subjects

Pankaj Mehta

Publications and source records attributed to Pankaj Mehta.

At least 55 records · Page 3Linked to original sources

arXiv2018

The strength of protein-protein interactions controls the information capacity and dynamical response of signaling networks

Eukaryotic cells transmit information by signaling through complex networks of interacting proteins. Here we develop a theoretical and computational framework that relates the biophysics of protein-protein interactions (PPIs) within a signaling network to its information processing properties. To do so, we generalize statistical physics-inspired models for protein binding to account for interactions that depend on post-translational state (e.g. phosphorylation). By combining these models with information-theoretic methods, we find that PPIs are a key determinant of information transmission within a signaling network, with weak interactions giving rise to "noise" that diminishes information transmission. While noise can be mitigated by increasing interaction strength, the accompanying increase in transmission comes at the expense of a slower dynamical response. This suggests that the biophysics of signaling protein interactions give rise to a fundamental "speed-information" trade-off. Surprisingly, we find that cross-talk between pathways in complex signaling networks do not significantly alter information capacity--an observation that may partially explain the promiscuity and ubiquity of weak PPIs in heavily interconnected networks. We conclude by showing how our framework can be used to design synthetic biochemical networks that maximize information transmission, a procedure we dub "InfoMax" design.

q-bio.MN↗

arXiv2018

Reinforcement Learning in Different Phases of Quantum Control

The ability to prepare a physical system in a desired quantum state is central to many areas of physics such as nuclear magnetic resonance, cold atoms, and quantum computing. Yet, preparing states quickly and with high fidelity remains a formidable challenge. In this work we implement cutting-edge Reinforcement Learning (RL) techniques and show that their performance is comparable to optimal control methods in the task of finding short, high-fidelity driving protocol from an initial to a target state in non-integrable many-body quantum systems of interacting qubits. RL methods learn about the underlying physical system solely through a single scalar reward (the fidelity of the resulting state) calculated from numerical simulations of the physical system. We further show that quantum state manipulation, viewed as an optimization problem, exhibits a spin-glass-like phase transition in the space of protocols as a function of the protocol duration. Our RL-aided approach helps identify variational protocols with nearly optimal fidelity, even in the glassy phase, where optimal state manipulation is exponentially hard. This study highlights the potential usefulness of RL for applications in out-of-equilibrium quantum physics.

quant-ph↗

arXiv2018

Constrained optimization as ecological dynamics with applications to random quadratic programming in high dimensions

Quadratic programming (QP) is a common and important constrained optimization problem. Here, we derive a surprising duality between constrained optimization with inequality constraints -- of which QP is a special case -- and consumer resource models describing ecological dynamics. Combining this duality with a recent `cavity solution', we analyze high-dimensional, random QP where the optimization function and constraints are drawn randomly. Our theory shows remarkable agreement with numerics and points to a deep connection between optimization, dynamical systems, and ecology.

cond-mat.stat-mech↗

arXiv2018

Identifying feasible operating regimes for early T-cell recognition: The speed, energy, accuracy trade-off in kinetic proofreading and adaptive sorting

In the immune system, T cells can quickly discriminate between foreign and self ligands with high accuracy. There is evidence that T-cells achieve this remarkable performance utilizing a network architecture based on a generalization of kinetic proofreading (KPR). KPR-based mechanisms actively consume energy to increase the specificity beyond what is possible in equilibrium.An important theoretical question that arises is to understand the trade-offs and fundamental limits on accuracy, speed, and dissipation (energy consumption) in KPR and its generalization. Here, we revisit this question through numerical simulations where we simultaneously measure the speed, accuracy, and energy consumption of the KPR and adaptive sorting networks for different parameter choices. Our simulations highlight the existence of a 'feasible operating regime' in the speed-energy-accuracy plane where T-cells can quickly differentiate between foreign and self ligands at reasonable energy expenditure. We give general arguments for why we expect this feasible operating regime to be a generic property of all KPR-based biochemical networks and discuss implications for our understanding of the T cell receptor circuit.

q-bio.MN↗

arXiv2018

Broken symmetry in a two-qubit quantum control landscape

We analyze the physics of optimal protocols to prepare a target state with high fidelity in a symmetrically coupled two-qubit system. By varying the protocol duration, we find a discontinuous phase transition, which is characterized by a spontaneous breaking of a $\mathbb{Z}_2$ symmetry in the functional form of the optimal protocol, and occurs below the quantum speed limit. We study in detail this phase and demonstrate that even though high-fidelity protocols come degenerate with respect to their fidelity, they lead to final states of different entanglement entropy shared between the qubits. Consequently, while globally both optimal protocols are equally far away from the target state, one is locally closer than the other. An approximate variational mean-field theory which captures the physics of the different phases is developed.

cond-mat.stat-mech↗

arXiv2017

Geometry and non-adiabatic response in quantum and classical systems

In these lecture notes, partly based on a course taught at the Karpacz Winter School in March 2014, we explore the close connections between non-adiabatic response of a system with respect to macroscopic parameters and the geometry of quantum and classical states. We center our discussion around adiabatic gauge potentials, which are the generators of unitary basis transformations in quantum systems and generators of special canonical transformations in classical systems. In quantum systems, eigenstate expectation values of these potentials are the Berry connections and the covariance matrix of these gauge potentials is the geometric tensor, whose antisymmetric part defines the Berry curvature and whose symmetric part is the Fubini-Study metric tensor. In classical systems one simply replaces the eigenstate expectation value by an average over the micro-canonical shell. For complicated interacting systems, we show that a variational principle may be used to derive approximate gauge potentials. We then express the non-adiabatic response of the physical observables of the system through these gauge potentials, specifically demonstrating the close connection of the geometric tensor to the notions of Lorentz force and renormalized mass. We highlight applications of this formalism to deriving counter-diabatic (dissipationless) driving protocols in various systems, as well as to finding equations of motion for slow macroscopic parameters coupled to fast microscopic degrees of freedom that go beyond macroscopic Hamiltonian dynamics. Finally, we illustrate these ideas with a number of simple examples and highlight a few more complicated ones drawn from recent literature.

cond-mat.quant-gas↗

arXiv2017

Environmental engineering is an emergent feature of diverse ecosystems and drives community structure

A central question in ecology is to understand the ecological processes that shape community structure. Niche-based theories have emphasized the important role played by competition for maintaining species diversity. Many of these insights have been derived using MacArthur's consumer resource model (MCRM) or its generalizations. Most theoretical work on the MCRM has focused on small ecosystems with a few species and resources. However theoretical insights derived from small ecosystems many not scale up large ecosystems with many resources and species because large systems with many interacting components often display new emergent behaviors that cannot be understood or deduced from analyzing smaller systems. To address this shortcoming, we develop a sophisticated statistical physics inspired cavity method to analyze MCRM when both the number of species and the number of resources is large. We find that in this limit, species generically and consistently perturb their environments and significantly modify available ecological niches. We show how our cavity approach naturally generalizes niche theory to large ecosystems by accounting for the effect of this emergent environmental engineering on species invasion and ecological stability. Our work suggests that environmental engineering is a generic feature of large, natural ecosystems and must be taken into account when analyzing and interpreting community structure. It also highlights the important role that statistical-physics inspired approaches can play in furthering our understanding of ecology.

q-bio.PE↗

arXiv2017

A thermodynamic paradigm for solution demixing inspired by nuclear transport in living cells

Living cells display a remarkable capacity to compartmentalize their functional biochemistry. A particularly fascinating example is the cell nucleus. Exchange of macromolecules between the nucleus and the surrounding cytoplasm does not involve traversing a lipid bilayer membrane. Instead, large protein channels known as nuclear pores cross the nuclear envelope and regulate the passage of other proteins and RNA molecules. Beyond simply gating diffusion, the system of nuclear pores and associated transport receptors is able to generate substantial concentration gradients, at the energetic expense of guanosine triphosphate (GTP) hydrolysis. In contrast to conventional approaches to demixing such as reverse osmosis or dialysis, the biological system operates continuously, without application of cyclic changes in pressure or solvent exchange. Abstracting the biological paradigm, we examine this transport system as a thermodynamic machine of solution demixing. Building on the construct of free energy transduction and biochemical kinetics, we find conditions for stable operation and optimization of the concentration gradients as a function of dissipation in the form of entropy production.

q-bio.SC↗

arXiv2016

Controlling energy landscapes with correlations between minima

Neural network models have been used to construct energy landscapes for modeling biological phenomena, in which the minima of the landscape correspond to memory patterns stored by the network. Here, we show that dynamic properties of those landscapes, such as the sizes of the basins of attraction and the density of stable and metastable states, depend strongly on the correlations between the memory patterns and can be altered by introducing hierarchical structures. Our findings suggest dynamic features of energy landscapes can be controlled by choosing the correlations between patterns

cond-mat.dis-nn↗

arXiv2016

Comment on "Why does deep and cheap learning work so well?" [arXiv:1608.08225]

In a recent paper, "Why does deep and cheap learning work so well?", Lin and Tegmark claim to show that the mapping between deep belief networks and the variational renormalization group derived in [arXiv:1410.3831] is invalid, and present a "counterexample" that claims to show that this mapping does not hold. In this comment, we show that these claims are incorrect and stem from a misunderstanding of the variational RG procedure proposed by Kadanoff. We also explain why the "counterexample" of Lin and Tegmark is compatible with the mapping proposed in [arXiv:1410.3831].

cond-mat.dis-nn↗

arXiv2015

An analytically tractable model for community ecology with many species

A fundamental problem in community ecology is to understand how ecological processes such as selection, drift, and immigration give rise to observed patterns in species composition and diversity. Here, we present a simple, analytically tractable, presence-absence (PA) model for community assembly and use it to ask how ecological traits such as the strength of competition, the amount of diversity, and demographic and environmental stochasticity affect species composition in a community. In the PA model, species are treated as stochastic binary variables that can either be present or absent in a community: species can immigrate into the community from a regional species pool and can go extinct due to competition and stochasticity. Despite its simplicity, the PA model reproduces the qualitative features of more complicated models of community assembly. In agreement with recent work on large, competitive Lotka-Volterra systems, the PA model exhibits distinct ecological behaviors organized around a special ("critical") point corresponding to Hubbell's neutral theory of biodiversity. These results suggest that the concepts of ecological "phases" and phase diagrams can provide a powerful framework for thinking about community ecology and that the PA model captures the essential ecological dynamics of community assembly.

q-bio.PE↗

arXiv2015

Cellular reprogramming dynamics follow a simple one-dimensional reaction coordinate

Cellular reprogramming, the conversion of one cell type to another, has fundamentally transformed our conception of cell types. Cellular reprogramming induces global changes in gene expression involving hundreds of transcription factors and thousands of genes and understanding how cells globally alter their gene expression profile during reprogramming is an open problem. Here we reanalyze time-series data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple one-dimensional reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges naturally from epigenetic landscape models of cell identity where cellular reprogramming is viewed as a "barrier-crossing" between the starting and ending cell fates. The model also provides gene-level insight into reprogramming dynamics and resolves a debate in the stem cell field about the different phases of reprogramming dynamics. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an "optimal path" in gene expression space for reprogramming.

q-bio.MN↗

arXiv2015

Landauer in the age of synthetic biology: energy consumption and information processing in biochemical networks

A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.

q-bio.MN↗

arXiv2014

Bayesian feature selection with strongly-regularizing priors maps to the Ising Model

Identifying small subsets of features that are relevant for prediction and/or classification tasks is a central problem in machine learning and statistics. The feature selection task is especially important, and computationally difficult, for modern datasets where the number of features can be comparable to, or even exceed, the number of samples. Here, we show that feature selection with Bayesian inference takes a universal form and reduces to calculating the magnetizations of an Ising model, under some mild conditions. Our results exploit the observation that the evidence takes a universal form for strongly-regularizing priors --- priors that have a large effect on the posterior probability even in the infinite data limit. We derive explicit expressions for feature selection for generalized linear models, a large class of statistical techniques that include linear and logistic regression. We illustrate the power of our approach by analyzing feature selection in a logistic regression-based classifier trained to distinguish between the letters B and D in the notMNIST dataset.

cond-mat.stat-mech↗

arXiv2014

An exact mapping between the Variational Renormalization Group and Deep Learning

Deep learning is a broad set of techniques that uses multiple layers of representation to automatically learn relevant features directly from structured data. Recently, such techniques have yielded record-breaking results on a diverse set of difficult machine learning tasks in computer vision, speech recognition, and natural language processing. Despite the enormous success of deep learning, relatively little is understood theoretically about why these techniques are so successful at feature learning and compression. Here, we show that deep learning is intimately related to one of the most important and successful techniques in theoretical physics, the renormalization group (RG). RG is an iterative coarse-graining scheme that allows for the extraction of relevant features (i.e. operators) as a physical system is examined at different length scales. We construct an exact mapping from the variational renormalization group, first introduced by Kadanoff, and deep learning architectures based on Restricted Boltzmann Machines (RBMs). We illustrate these ideas using the nearest-neighbor Ising Model in one and two-dimensions. Our results suggests that deep learning algorithms may be employing a generalized RG-like scheme to learn relevant features from data.

stat.ML↗

arXiv2014

Thermodynamics of statistical inference by cells

The deep connection between thermodynamics, computation, and information is now well established both theoretically and experimentally. Here, we extend these ideas to show that thermodynamics also places fundamental constraints on statistical estimation and learning. To do so, we investigate the constraints placed by (nonequilibrium) thermodynamics on the ability of biochemical signaling networks within cells to estimate the concentration of an external signal. We show that accuracy is limited by energy consumption, suggesting that there are fundamental thermodynamic constraints on statistical inference.

physics.bio-ph↗

arXiv2014

Multiscale modeling of oscillations and spiral waves in Dictyostelium populations

Unicellular organisms exhibit elaborate collective behaviors in response to environmental cues. These behaviors are controlled by complex biochemical networks within individual cells and coordinated through cell-to-cell communication. Describing these behaviors requires new mathematical models that can bridge scales -- from biochemical networks within individual cells to spatially structured cellular populations. Here, we present a family of multiscale models for the emergence of spiral waves in the social amoeba Dictyostelium discoideum. Our models exploit new experimental advances that allow for the direct measurement and manipulation of the small signaling molecule cAMP used by Dictyostelium cells to coordinate behavior in cellular populations. Inspired by recent experiments, we model the Dictyostelium signaling network as an excitable system coupled to various pre-processing modules. We use this family of models to study spatially unstructured populations by constructing phase diagrams that relate the properties of population-level oscillations to parameters in the underlying biochemical network. We then extend our models to include spatial structure and show how they naturally give rise to spiral waves. Our models exhibit a wide range of novel phenomena including a density dependent frequency change, bistability, and dynamic death due to slow cAMP dynamics. Our modeling approach provides a powerful tool for bridging scales in modeling of Dictyostelium populations.

q-bio.CB↗

arXiv2014

Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes

A common metaphor for describing development is a rugged "epigenetic landscape" where cell fates are represented as attracting valleys resulting from a complex regulatory network. Here, we introduce a framework for explicitly constructing epigenetic landscapes that combines genomic data with techniques from spin-glass physics. Each cell fate is a dynamic attractor, yet cells can change fate in response to external signals. Our model suggests that partially reprogrammed cells are a natural consequence of high-dimensional landscapes, and predicts that partially reprogrammed cells should be hybrids that co-express genes from multiple cell fates. We verify this prediction by reanalyzing existing datasets. Our model reproduces known reprogramming protocols and identifies candidate transcription factors for reprogramming to novel cell fates, suggesting epigenetic landscapes are a powerful paradigm for understanding cellular identity.

q-bio.MN↗