arXiv subjects

William Bialek

Publications and source records attributed to William Bialek.

At least 37 records · Page 2Linked to original sources

arXiv2023

Scale invariance in early embryonic development

The body plan of the fruit fly is determined by the expression of just a handful of genes. We show that the spatial patterns of expression for several of these genes scale precisely with the size of the embryo. Concretely, discrete positional markers such as the peaks in striped patterns have absolute positions along the anterior-posterior axis that are proportional to embryo length, with better than 1% accuracy. Further, the information (in bits) that graded patterns of expression provide about position can be decomposed into information about fractional or scaled position and information about absolute position or embryo length; all of the available information is about scaled position, again with ~1% accuracy. These observations suggest that the underlying genetic network exhibits scale invariance in a deeper mathematical sense. Taking this mathematical statement seriously requires that the network dynamics have a zero mode, which connects to many other observations on this system.

q-bio.MN↗

arXiv2023

Exact minimax entropy models of large-scale neuronal activity

In the brain, fine-scale correlations combine to produce macroscopic patterns of activity. However, as experiments record from larger and larger populations, we approach a fundamental bottleneck: the number of correlations one would like to include in a model grows larger than the available data. In this undersampled regime, one must focus on a sparse subset of correlations; the optimal choice contains the maximum information about patterns of activity or, equivalently, minimizes the entropy of the inferred maximum entropy model. Applying this ``minimax entropy" principle is generally intractable, but here we present an exact and scalable solution for pairwise correlations that combine to form a tree (a network without loops). Applying our method to over one thousand neurons in the mouse hippocampus, we find that the optimal tree of correlations reduces our uncertainty about the population activity by 14% (over 50 times more than a random tree). Despite containing only 0.1% of all pairwise correlations, this minimax entropy model accurately predicts the observed large-scale synchrony in neural activity and becomes even more accurate as the population grows. The inferred Ising model is almost entirely ferromagnetic (with positive interactions) and exhibits signatures of thermodynamic criticality. These results suggest that a sparse backbone of excitatory interactions may play an important role in driving collective neuronal activity.

physics.bio-ph↗

arXiv2023

Finding the last bits of positional information

In a developing embryo, information about the position of cells is encoded in the concentrations of "morphogen" molecules. In the fruit fly, the local concentrations of just a handful of proteins encoded by the gap genes are sufficient to specify position with a precision comparable to the spacing between cells along the anterior--posterior axis. This matches the precision of downstream events such as the striped patterns of expression in the pair-rule genes, but is not quite sufficient to define unique identities for individual cells. We demonstrate theoretically that this information gap can be bridged if positional errors are spatially correlated, with relatively long correlation lengths. We then show experimentally that these correlations are present, with the required strength, in the fluctuating positions of the pair-rule stripes, and this can be traced back to the gap genes. Taking account of these correlations, the available information matches the information needed for unique cellular specification, within error bars of ~2%. These observation support a precisionist view of information flow through the underlying genetic networks, in which accurate signals are available from the start and preserved as they are transformed into the final spatial patterns.

q-bio.MN↗

arXiv2023

Deriving a genetic regulatory network from an optimization principle

Many biological systems approach physical limits to their performance, motivating the idea that their behavior and underlying mechanisms could be determined by such optimality. Nevertheless, optimization as a predictive principle has only been applied in very simplified setups. Here, in contrast, we explore a mechanistically-detailed class of models for the gap gene network of the Drosophila embryo, and determine its 50+ parameters by optimizing the information that gene expression levels convey about nuclear positions, subject to physical constraints on the number of available molecules. Optimal networks recapitulate the architecture and spatial gene expression profiles of the real organism. Our framework makes precise the many tradeoffs involved in maximizing functional performance, and allows us to explore alternative networks to address the questions of necessity vs contingency. Multiple solutions to the optimization problem may be realized in closely related organisms.

physics.bio-ph↗

arXiv2023

Exactly solvable statistical physics models for large neuronal populations

Maximum entropy methods provide a principled path connecting measurements of neural activity directly to statistical physics models, and this approach has been successful for populations of $N\sim 100$ neurons. As $N$ increases in new experiments, we enter an undersampled regime where we have to choose which observables should be constrained in the maximum entropy construction. The best choice is the one that provides the greatest reduction in entropy, defining a "minimax entropy" principle. This principle becomes tractable if we restrict attention to correlations among pairs of neurons that link together into a tree; we can find the best tree efficiently, and the underlying statistical physics models are exactly solved. We use this approach to analyze experiments on $N\sim 1500$ neurons in the mouse hippocampus, and show that the resulting model captures the distribution of synchronous activity in the network.

physics.bio-ph↗

arXiv2023

Keith Brueckner (1924-2014). A biographical memoir

Keith Brueckner was a theoretical physicist of considerable technical power who came of age as the mysteries of the atomic nucleus were coming into focus. His fundamental contributions to the "many-body problem" had a lasting impact on our understanding of how the macroscopic behavior of matter emerges from the underlying microscopic rules. A passionate and accomplished mountain climber, he listed the American Alpine Club below the National Academy of Sciences on his vitae. During decades of complex interactions between the physics community and the United States government, he helped build structures that allowed him and many others to provide advice on classified matters, but also actively raised funds to support opposition to the war in Vietnam. At the peak of his career, he left the Ivy League to help found and build a new university in a small village filled with Marines and retirees - La Jolla, California.

physics.hist-ph↗

arXiv2023

Successes and failures of simple statistical physics models for a network of real neurons

Biological networks exhibit complex, coordinated patterns of activity. Can these patterns be captured precisely in simple models? Here we use measurements of simultaneous activity in 1000+ neurons in the mouse brain to test the validity of models grounded in statistical physics. When cells are dense samples from a small region, we find extremely detailed quantitative agreement between theory and experiment; sparse samples from larger regions lead to model failures. These results show we can aspire to more than qualitative agreement between simplifying theoretical ideas and the detailed behavior of a complex biological system.

physics.bio-ph↗

arXiv2023

Long time scales, individual differences, and scale invariance in animal behavior

The explosion of data on animal behavior in more natural contexts highlights the fact that these behaviors exhibit correlations across many time scales. But there are major challenges in analyzing these data: records of behavior in single animals have fewer independent samples than one might expect; in pooling data from multiple animals, individual differences can mimic long-ranged temporal correlations; conversely long-ranged correlations can lead to an over-estimate of individual differences. We suggest an analysis scheme that addresses these problems directly, apply this approach to data on the spontaneous behavior of walking flies, and find evidence for scale invariant correlations over nearly three decades in time, from seconds to one hour. Three different measures of correlation are consistent with a single underlying scaling field of dimension $Δ= 0.180\pm 0.005$.

q-bio.NC↗

arXiv2022

How accurately must cells measure the concentrations of signaling molecules?

Information of relevance to the organism often is represented by the concentrations of particular molecules inside a cell. As outside observers we can now measure these concentrations precisely, but the cell's own mechanisms must be noisier. We show that, in certain limits, there is a universal tradeoff between the information capacity of these concentration measurements and the amount of relevant information that is captured, a version of the information bottleneck problem. This universal tradeoff is confirmed, quantitatively, in an analysis of the positional information encoded by the gap genes in the developing fly embryo.

physics.bio-ph↗

arXiv2022

Emergence of local irreversibility in complex interacting systems

Living systems are fundamentally irreversible, breaking detailed balance and establishing an arrow of time. But how does the evident arrow of time for a whole system arise from the interactions among its multiple elements? We show that the local evidence for the arrow of time, which is the entropy production for thermodynamic systems, can be decomposed. First, it can be split into two components: an independent term reflecting the dynamics of individual elements and an interaction term driven by the dependencies among elements. Adapting tools from non--equilibrium physics, we further decompose the interaction term into contributions from pairs of elements, triplets, and higher--order terms. We illustrate our methods on models of cellular sensing and logical computations, as well as on patterns of neural activity in the retina as it responds to visual inputs. We find that neural activity can define the arrow of time even when the visual inputs do not, and that the dominant contribution to this breaking of detailed balance comes from interactions among pairs of neurons.

cond-mat.stat-mech↗

arXiv2022

Decomposing the local arrow of time in interacting systems

We show that the evidence for a local arrow of time, which is equivalent to the entropy production in thermodynamic systems, can be decomposed. In a system with many degrees of freedom, there is a term that arises from the irreversible dynamics of the individual variables, and then a series of non--negative terms contributed by correlations among pairs, triplets, and higher--order combinations of variables. We illustrate this decomposition on simple models of noisy logical computations, and then apply it to the analysis of patterns of neural activity in the retina as it responds to complex dynamic visual scenes. We find that neural activity breaks detailed balance even when the visual inputs do not, and that this irreversibility arises primarily from interactions between pairs of neurons.

cond-mat.stat-mech↗

arXiv2020

Exploring a strongly non-Markovian animal behavior

A freely walking fly visits roughly 100 stereotyped states in a strongly non-Markovian sequence. To explore these dynamics, we develop a generalization of the information bottleneck method, compressing the large number of behavioral states into a more compact description that maximally preserves the correlations between successive states. Surprisingly, preserving these short time correlations with a compression into just two states captures the long ranged correlations seen in the raw data. Having reduced the behavior to a binary sequence, we describe the distribution of these sequences by an Ising model with pairwise interactions, which is the maximum entropy model that matches the two-point correlations. Matching the correlation function at longer and longer times drives the resulting model toward the Ising model with inverse square interactions and near zero magnetic field. The emergence of this statistical physics problem from the analysis real data on animal behavior is unexpected.

q-bio.NC↗

arXiv2020

Transcription-dependent spatial organization of a gene locus

There is growing appreciation that gene function is connected to the dynamic structure of the chromosome. Here we explore the interplay between three-dimensional structure and transcriptional activity at the single cell level. We show that inactive loci are spatially more compact than active ones, and that within active loci the enhancer driving transcription is closest to the promoter. On the other hand, even this shortest distance is too long to support direct physical contact between the enhancer-promoter pair when the locus is transcriptionally active. Artificial manipulation of genomic separations between enhancers and the promoter produces changes in physical distance and transcriptional activity, recapitulating the correlation seen in wild-type embryos, but disruption of topological domain boundaries has no effect. Our results suggest a complex interdependence between transcription and the spatial organization of cis-regulatory elements.

q-bio.MN↗

arXiv2020

Trading bits in the readout from a genetic network

In genetic networks, information of relevance to the organism is represented by the concentrations of transcription factor molecules. In order to extract this information the cell must effectively "measure"' these concentrations, but there are physical limits to the precision of these measurements. We explore this trading between bits of precision in measuring concentration and bits of relevant information that can be extracted, using the gap gene network in the early fly embryo as an example. We argue that cells in the embryo can extract all the available information about their position, but only if the concentration measurements approach the physical limits to information capacity. These limits necessitate the observed proliferation of enhancer elements with sensitivities to combinations of transcription factors, but fine tuning of the parameters of these multiple enhancers is not required.

q-bio.MN↗

arXiv2020

Searching for sequence features that control DNA flexibility

Modern genomics experiments measure functional behaviors for many thousands of DNA sequences. We suggest that, especially when these sequences are chosen at random, it is natural to compute correlation functions between sequences and measured behaviors. In simple models for the dependence of DNA flexibility on sequence, for example, correlation functions can be interpreted directly as interaction parameters. Analysis of recent experiments shows that this is surprisingly effective, leading directly to extraction of distinct features for DNA flexibility and predictions that are as accurate as more complex models. This approach follows the conventional use of correlation functions in statistical physics and connects the search for relevant DNA sequence features to the search for relevant stimulus features in the analysis of sensory neurons.

physics.bio-ph↗

arXiv2020

What do we mean by the dimensionality of behavior?

There is growing effort in the "physics of behavior" that aims at complete quantitative characterization of animal movements under more complex, naturalistic conditions. One reaction to the resulting explosion of data is the search for low dimensional structure. Here I try to define more clearly what we mean by the dimensionality of behavior, where observable behavior may consist either of continuous trajectories or sequences of discrete states. This discussion also serves to isolate situations in which the dimensionality of behavior is effectively infinite. I conclude with some more general perspectives about the importance of quantitative phenomenology.

q-bio.NC↗

arXiv2019

Information costs in the control of protein synthesis

Efficient protein synthesis depends on the availability of charged tRNA molecules. With 61 different codons, shifting the balance among the tRNA abundances can lead to large changes in the protein synthesis rate. Previous theoretical work has asked about the optimization of these abundances, and there is some evidence that regulatory mechanisms bring cells close to this optimum, on average. We formulate the tradeoff between the precision of control and the efficiency of synthesis, asking for the maximum entropy distribution of tRNA abundances consistent with a desired mean rate of protein synthesis. Our analysis, using data from E. coli, indicates that reasonable synthesis rates are consistent only with rather low entropies, so that the cell's regulatory mechanisms must encode a large amount of information about the "correct" tRNA abundances.

q-bio.SC↗

arXiv2019

Action at a distance in transcriptional regulation

There is increasing evidence that protein binding to specific sites along DNA can activate the reading out of genetic information without coming into direct physical contact with the gene. There also is evidence that these distant but interacting sites are embedded in a liquid droplet of proteins which condenses out of the surrounding solution. We argue that droplet-mediated interactions can account for crucial features of gene regulation only if the droplet is poised at a non-generic point in its phase diagram. We explore a minimal model that embodies this idea, show that this model has a natural mechanism for self-tuning, and suggest direct experimental tests.

q-bio.SC↗