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Uri Alon

Publications and source records attributed to Uri Alon.

48 records · Page 3Linked to original sources

Creative Foraging: A Quantitative Paradigm for Studying Creative Exploration

Creative exploration is central to science, art and cognitive development. However, research on creative exploration is limited by a lack of high-resolution automated paradigms. To address this, we present such an automated paradigm, the creative foraging game, in which people search for novel and valuable solutions in a large and well-defined space made of all possible shapes made of ten connected squares. Players discovered shape categories such as digits, letters, and airplanes. They exploited each category, then dropped it to explore once again, and so on. Aligned with a prediction of optimal foraging theory (OFT) prediction, during exploration phases, people moved along meandering paths that are about three times longer than the minimal paths between shapes, when exploiting a category of related shapes, they moved along the minimal paths. The moment of discovery of a new category was usually done at a nonprototypical and ambiguous shape, which can serve as an experimental proxy for creative leaps. People showed individual differences in their search patterns, along a continuum between two strategies: a mercurial quick-to-discover/quick-to-drop strategy and a thorough slow-to-discover/slow-to-drop strategy. Contrary to optimal foraging theory, players leave exploitation to explore again far before categories are depleted. This paradigm opens the way for automated high-resolution study of creative exploration.

q-bio.NC↗

Evolution of bow-tie architectures in biology

Bow-tie or hourglass structure is a common architectural feature found in biological and technological networks. A bow-tie in a multi-layered structure occurs when intermediate layers have much fewer components than the input and output layers. Examples include metabolism where a handful of building blocks mediate between multiple input nutrients and multiple output biomass components, and signaling networks where information from numerous receptor types passes through a small set of signaling pathways to regulate multiple output genes. Little is known, however, about how bow-tie architectures evolve. Here, we address the evolution of bow-tie architectures using simulations of multi-layered systems evolving to fulfill a given input-output goal. We find that bow-ties spontaneously evolve when two conditions are met: (i) the evolutionary goal is rank deficient, where the rank corresponds to the minimal number of input features on which the outputs depend, and (ii) The effects of mutations on interaction intensities between components are described by product rule - namely the mutated element is multiplied by a random number. Product-rule mutations are more biologically realistic than the commonly used sum-rule mutations that add a random number to the mutated element. These conditions robustly lead to bow-tie structures. The minimal width of the intermediate network layers (the waist or knot of the bow-tie) equals the rank of the evolutionary goal. These findings can help explain the presence of bow-ties in diverse biological systems, and can also be relevant for machine learning applications that employ multi-layered networks.

q-bio.MN↗

Mutation Rules and the Evolution of Sparseness and Modularity in Biological Systems

Biological systems exhibit two structural features on many levels of organization: sparseness, in which only a small fraction of possible interactions between components actually occur; and modularity - the near decomposability of the system into modules with distinct functionality. Recent work suggests that modularity can evolve in a variety of circumstances, including goals that vary in time such that they share the same subgoals (modularly varying goals), or when connections are costly. Here, we studied the origin of modularity and sparseness focusing on the nature of the mutation process, rather than on connection cost or variations in the goal. We use simulations of evolution with different mutation rules. We found that commonly used sum-rule mutations, in which interactions are mutated by adding random numbers, do not lead to modularity or sparseness except for in special situations. In contrast, product-rule mutations in which interactions are mutated by multiplying by random numbers - a better model for the effects of biological mutations - led to sparseness naturally. When the goals of evolution are modular, in the sense that specific groups of inputs affect specific groups of outputs, product-rule mutations also lead to modular structure; sum-rule mutations do not. Product-rule mutations generate sparseness and modularity because they tend to reduce interactions, and to keep small interaction terms small.

q-bio.MN↗

Entrainment of noise-induced and limit cycle oscillators under weak noise

Theoretical models that describe oscillations in biological systems are often either a limit cycle oscillator, where the deterministic nonlinear dynamics gives sustained periodic oscillations, or a noise-induced oscillator, where a fixed point is linearly stable with complex eigenvalues and addition of noise gives oscillations around the fixed point with fluctuating amplitude. We investigate how each class of model behaves under the external periodic forcing, taking the well-studied van der Pol equation as an example. We find that, when the forcing is additive, the noise-induced oscillator can show only one-to-one entrainment to the external frequency, in contrast to the limit cycle oscillator which is known to entrain to any ratio. When the external forcing is multiplicative, on the other hand, the noise-induced oscillator can show entrainment to a few ratios other than one-to-one, while the limit cycle oscillator shows entrain to any ratio. The noise blurs the entrainment in general, but clear entrainment regions for limit cycles can be identified as long as the noise is not too strong.

q-bio.QM↗

Symmetry invariance for adapting biological systems

We study in this paper certain properties of the responses of dynamical systems to external inputs. The motivation arises from molecular systems biology. and, in particular, the recent discovery of an important transient property, related to Weber's law in psychophysics: "fold-change detection" in adapting systems, the property that scale uncertainty does not affect responses. FCD appears to play an important role in key signaling transduction mechanisms in eukaryotes, including the ERK and Wnt pathways, as well as in E.coli and possibly other prokaryotic chemotaxis pathways. In this paper, we provide further theoretical results regarding this property. Far more generally, we develop a necessary and sufficient characterization of adapting systems whose transient behaviors are invariant under the action of a set (often, a group) of symmetries in their sensory field. A particular instance is FCD, which amounts to invariance under the action of the multiplicative group of positive real numbers. Our main result is framed in terms of a notion which extends equivariant actions of compact Lie groups. Its proof relies upon control theoretic tools, and in particular the uniqueness theorem for minimal realizations.

eess.SY↗

Rules for biological regulation based on error minimization

The control of gene expression involves complex mechanisms that show large variation in design. For example, genes can be turned on either by the binding of an activator (positive control) or the unbinding of a repressor (negative control). What determines the choice of mode of control for each gene? This study proposes rules for gene regulation based on the assumption that free regulatory sites are exposed to nonspecific binding errors, whereas sites bound to their cognate regulators are protected from errors. Hence, the selected mechanisms keep the sites bound to their designated regulators for most of the time, thus minimizing fitness-reducing errors. This offers an explanation of the empirically demonstrated Savageau demand rule: Genes that are needed often in the natural environment tend to be regulated by activators, and rarely needed genes tend to be regulated by repressors; in both cases, sites are bound for most of the time, and errors are minimized. The fitness advantage of error minimization appears to be readily selectable. The present approach can also generate rules for multi-regulator systems. The error-minimization framework raises several experimentally testable hypotheses. It may also apply to other biological regulation systems, such as those involving protein-protein interactions.

q-bio.BM↗

Coding limits on the number of transcription factors

Transcription factor proteins bind specific DNA sequences to control the expression of genes. They contain DNA binding domains which belong to several super-families, each with a specific mechanism of DNA binding. The total number of transcription factors encoded in a genome increases with the number of genes in the genome. Here, we examined the number of transcription factors from each super-family in diverse organisms. We find that the number of transcription factors from most super-families appears to be bounded. For example, the number of winged helix factors does not generally exceed 300, even in very large genomes. The magnitude of the maximal number of transcription factors from each super-family seems to correlate with the number of DNA bases effectively recognized by the binding mechanism of that super-family. Coding theory predicts that such upper bounds on the number of transcription factors should exist, in order to minimize cross-binding errors between transcription factors. This theory further predicts that factors with similar binding sequences should tend to have similar biological effect, so that errors based on mis-recognition are minimal. We present evidence that transcription factors with similar binding sequences tend to regulate genes with similar biological functions, supporting this prediction. The present study suggests limits on the transcription factor repertoire of cells, and suggests coding constraints that might apply more generally to the mapping between binding sites and biological function.

q-bio.BM↗

Coarse-Graining and Self-Dissimilarity of Complex Networks

Can complex engineered and biological networks be coarse-grained into smaller and more understandable versions in which each node represents an entire pattern in the original network? To address this, we define coarse-graining units (CGU) as connectivity patterns which can serve as the nodes of a coarse-grained network, and present algorithms to detect them. We use this approach to systematically reverse-engineer electronic circuits, forming understandable high-level maps from incomprehensible transistor wiring: first, a coarse-grained version in which each node is a gate made of several transistors is established. Then, the coarse-grained network is itself coarse-grained, resulting in a high-level blueprint in which each node is a circuit-module made of multiple gates. We apply our approach also to a mammalian protein-signaling network, to find a simplified coarse-grained network with three main signaling channels that correspond to cross-interacting MAP-kinase cascades. We find that both biological and electronic networks are 'self-dissimilar', with different network motifs found at each level. The present approach can be used to simplify a wide variety of directed and nondirected, natural and designed networks.

q-bio.MN↗

Subgraphs and network motifs in geometric networks

Many real-world networks describe systems in which interactions decay with the distance between nodes. Examples include systems constrained in real space such as transportation and communication networks, as well as systems constrained in abstract spaces such as multivariate biological or economic datasets and models of social networks. These networks often display network motifs: subgraphs that recur in the network much more often than in randomized networks. To understand the origin of the network motifs in these networks, it is important to study the subgraphs and network motifs that arise solely from geometric constraints. To address this, we analyze geometric network models, in which nodes are arranged on a lattice and edges are formed with a probability that decays with the distance between nodes. We present analytical solutions for the numbers of all 3 and 4-node subgraphs, in both directed and non-directed geometric networks. We also analyze geometric networks with arbitrary degree sequences, and models with a field that biases for directed edges in one direction. Scaling rules for scaling of subgraph numbers with system size, lattice dimension and interaction range are given. Several invariant measures are found, such as the ratio of feedback and feed-forward loops, which do not depend on system size, dimension or connectivity function. We find that network motifs in many real-world networks, including social networks and neuronal networks, are not captured solely by these geometric models. This is in line with recent evidence that biological network motifs were selected as basic circuit elements with defined information-processing functions.

cond-mat.stat-mech↗

Smooth Phases, Roughening Transitions and Novel Exponents in One-dimensional Growth Models

A class of solid-on-solid growth models with short range interactions and sequential updates is studied. The models exhibit both smooth and rough phases in dimension d=1. Some of the features of the roughening transition which takes place in these models are related to contact processes or directed percolation type problems. The models are analyzed using a mean field approximation, scaling arguments and numerical simulations. In the smooth phase the symmetry of the underlying dynamics is spontaneously broken. A family of order parameters which are not conserved by the dynamics is defined as well as conjugate fields which couple to these order parameters. The corresponding critical behavior is studied and novel exponents identified and measured. We also show how continuous symmetries can be broken in one dimension. A field theory appropriate for studying the roughening transition is introduced and discussed.

cond-mat.stat-mech↗

Gel-Electrophoresis and Diffusion of Ring-Shaped DNA

A model for the motion of ring-shaped DNA in a gel is introduced and studied by numerical simulations and a mean-field approximation. The ring motion is mediated by finger-shaped loops (hernias) that move in an amoeba-like fashion around the gel obstructions. This constitutes an extension of previous reptation tube treatments. It is shown that tension is essential for describing the dynamics in the presence of hernias. It is included in the model as long range interactions over stretched DNA regions. The mobility of ring-shaped DNA is found to saturate much as in the well-studied case of linear DNA. Experiments in polymer gels, however, show that the mobility drops exponentially with the DNA ring size. This is commonly attributed to dangling-ends in the gel that can impale the ring. The predictions of the present model are expected to apply to artificial 2D obstacle arrays (W.D. Volkmuth, R.H. Austin, Nature 358,600 (1992)) which have no dangling-ends. In the zero-field case an exact solution of the model steady-state is obtained, and quantities such as the average ring size are calculated. An approximate treatment of the ring dynamics is given, and the diffusion coefficient is derived. The model is also discussed in the context of spontaneous symmetry breaking in one dimension.

cond-mat.soft↗

Roughening Transition in a One-Dimensional Growth Process

A class of nonequilibrium models with short-range interactions and sequential updates is presented. The models describe one dimensional growth processes which display a roughening transition between a smooth and a rough phase. This transition is accompanied by spontaneous symmetry breaking, which is described by an order parameter whose dynamics is non-conserving. Some aspects of models in this class are related to directed percolation in 1+1 dimensions, although unlike directed percolation the models have no absorbing states. Scaling relations are derived and compared with Monte Carlo simulations.

cond-mat↗