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William Bialek

Publications and source records attributed to William Bialek.

At least 55 records · Page 3Linked to original sources

Coarse--graining and hints of scaling in a population of 1000+ neurons

In many systems we can describe emergent macroscopic behaviors, quantitatively, using models that are much simpler than the underlying microscopic interactions; we understand the success of this simplification through the renormalization group. Could similar simplifications succeed in complex biological systems? We develop explicit coarse-graining procedures that we apply to experimental data on the electrical activity in large populations of neurons in the mouse hippocampus. Probability distributions of coarse-grained variables seem to approach a fixed non-Gaussian form, and we see evidence of power-law dependencies in both static and dynamic quantities as we vary the coarse-graining scale over two decades. Taken together, these results suggest that the collective behavior of the network is described by a non-trivial fixed point.

physics.bio-ph↗

Optimal local estimates of visual motion in a natural environment

Many organisms, from flies to humans, use visual signals to estimate their motion through the world. To explore the motion estimation problem, we have constructed a camera/gyroscope system that allows us to sample, at high temporal resolution, the joint distribution of input images and rotational motions during a long walk in the woods. From these data we construct the optimal estimator of velocity based on spatial and temporal derivatives of image intensity in small patches of the visual world. Over the bulk of the naturally occurring dynamic range, the optimal estimator exhibits the same systematic errors seen in neural and behavioral responses, including the confounding of velocity and contrast. These results suggest that apparent errors of sensory processing may reflect an optimal response to the physical signals in the environment.

q-bio.NC↗

Precise spatial scaling in the early fly embryo

The early fly embryo offers a relatively pure version of the problem of spatial scaling in biological pattern formation. Within three hours, a "blueprint" for the final segmented body plan of the animal is visible in striped patterns of gene expression. We measure the positions of these stripes in an ensemble of 100+ embryos from a laboratory strain of Drosophila melanogaster, under controlled conditions. These embryos vary in length by only 4% (rms), yet stripes are positioned with 1% accuracy; precision and scaling of the pattern are intertwined. We can see directly the variation of absolute stripe positions with length, and the precision is so high as to exclude alternatives, such as combinations of unscaled signals from the two ends of the embryo.

q-bio.MN↗

The statistical mechanics of Twitter

We build models for the distribution of social states in Twitter communities. States can be defined by the participation vs silence of individuals in conversations that surround key words, and we approximate the joint distribution of these binary variables using the maximum entropy principle, finding the least structured models that match the mean probability of individuals tweeting and their pairwise correlations. These models provide very accurate, quantitative descriptions of higher order structure in these social networks. The parameters of these models seem poised close to critical surfaces in the space of possible models, and we observe scaling behavior of the data under coarse-graining. These results suggest that simple models, grounded in statistical physics, may provide a useful point of view on the larger data sets now emerging from complex social systems.

physics.soc-ph↗

Searching for collective behavior in a small brain

In large neuronal networks, it is believed that functions emerge through the collective behavior of many interconnected neurons. Recently, the development of experimental techniques that allow simultaneous recording of calcium concentration from a large fraction of all neurons in Caenorhabditis elegans - a nematode with 302 neurons - creates the opportunity to ask if such emergence is universal, reaching down to even the smallest brains. Here, we measure the activity of 50+ neurons in C. elegans, and analyze the data by building the maximum entropy model that matches the mean activity and pairwise correlations among these neurons. To capture the graded nature of the cells' responses, we assign each cell multiple states. These models, which are equivalent to a family of Potts glasses, successfully predict higher statistical structure in the network. In addition, these models exhibit signatures of collective behavior: the state of single cells can be predicted from the state of the rest of the network; the network, despite being sparse in a way similar to the structural connectome, distributes its response globally when locally perturbed; the distribution over network states has multiple local maxima, as in models for memory; and the parameters that describe the real network are close to a critical surface in this family of models.

physics.bio-ph↗

Coarse--graining, fixed points, and scaling in a large population of neurons

We develop a phenomenological coarse--graining procedure for activity in a large network of neurons, and apply this to recordings from a population of 1000+ cells in the hippocampus. Distributions of coarse--grained variables seem to approach a fixed non--Gaussian form, and we see evidence of scaling in both static and dynamic quantities. These results suggest that the collective behavior of the network is described by a non--trivial fixed point.

q-bio.NC↗

Collective behavior of place and non-place neurons in the hippocampal network

Discussions of the hippocampus often focus on place cells, but many neurons are not place cells in any given environment. Here we describe the collective activity in such mixed populations, treating place and non-place cells on the same footing. We start with optical imaging experiments on CA1 in mice as they run along a virtual linear track, and use maximum entropy methods to approximate the distribution of patterns of activity in the population, matching the correlations between pairs of cells but otherwise assuming as little structure as possible. We find that these simple models accurately predict the activity of each neuron from the state of all the other neurons in the network, regardless of how well that neuron codes for position. These and other results suggest that place cells are not a distinct sub-network, but part of a larger system that encodes, collectively, more than just place information.

q-bio.NC↗

Optimal decoding of information from a genetic network

Gene expression levels carry information about signals that have functional significance for the organism. Using the gap gene network in the fruit fly embryo as an example, we show how this information can be decoded, building a dictionary that translates expression levels into a map of implied positions. The optimal decoder makes use of graded variations in absolute expression level, resulting in positional estimates that are precise to ~1% of the embryo's length. We test this optimal decoder by analyzing gap gene expression in embryos lacking some of the primary maternal inputs to the network. The resulting maps are distorted, and these distortions predict, with no free parameters, the positions of expression stripes for the pair-rule genes in the mutant embryos.

q-bio.MN↗

PCA meets RG

A system with many degrees of freedom can be characterized by a covariance matrix; principal components analysis (PCA) focuses on the eigenvalues of this matrix, hoping to find a lower dimensional description. But when the spectrum is nearly continuous, any distinction between components that we keep and those that we ignore becomes arbitrary; it then is natural to ask what happens as we vary this arbitrary cutoff. We argue that this problem is analogous to the momentum shell renormalization group (RG). Following this analogy, we can define relevant and irrelevant operators, where the role of dimensionality is played by properties of the eigenvalue density. These results also suggest an approach to the analysis of real data. As an example, we study neural activity in the vertebrate retina as it responds to naturalistic movies, and find evidence of behavior controlled by a nontrivial fixed point. Applied to financial data, our analysis separates modes dominated by sampling noise from a smaller but still macroscopic number of modes described by a non--Gaussian distribution.

physics.bio-ph↗

Predictability and hierarchy in Drosophila behavior

Even the simplest of animals exhibit behavioral sequences with complex temporal dynamics. Prominent amongst the proposed organizing principles for these dynamics has been the idea of a hierarchy, wherein the movements an animal makes can be understood as a set of nested sub-clusters. Although this type of organization holds potential advantages in terms of motion control and neural circuitry, measurements demonstrating this for an animal's entire behavioral repertoire have been limited in scope and temporal complexity. Here, we use a recently developed unsupervised technique to discover and track the occurrence of all stereotyped behaviors performed by fruit flies moving in a shallow arena. Calculating the optimally predictive representation of the fly's future behaviors, we show that fly behavior exhibits multiple time scales and is organized into a hierarchical structure that is indicative of its underlying behavioral programs and its changing internal states.

physics.bio-ph↗

Perspectives on theory at the interface of physics and biology

Theoretical physics is the search for simple and universal mathematical descriptions of the natural world. In contrast, much of modern biology is an exploration of the complexity and diversity of life. For many, this contrast is prima facie evidence that theory, in the sense that physicists use the word, is impossible in a biological context. For others, this contrast serves to highlight a grand challenge. I'm an optimist, and believe (along with many colleagues) that the time is ripe for the emergence of a more unified theoretical physics of biological systems, building on successes in thinking about particular phenomena. In this essay I try to explain the reasons for my optimism, through a combination of historical and modern examples.

physics.bio-ph↗

Extending the dynamic range of transcription factor action by translational regulation

A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these molecules at their binding sites can severely limit the precision of regulation. Recent work on the optimization of information flow through regulatory networks indicates that the lower end of the dynamic range of concentrations is simply inaccessible, overwhelmed by the impact of this noise. Motivated by the behavior of homeodomain proteins, such as the maternal morphogen Bicoid in the fruit fly embryo, we suggest a scheme in which transcription factors also act as indirect translational regulators, binding to the mRNA of other transcription factors. Intuitively, each mRNA molecule acts as an independent sensor of the TF concentration, and averaging over these multiple sensors reduces the noise. We analyze information flow through this new scheme and identify conditions under which it outperforms direct transcriptional regulation. Our results suggest that the dual role of homeodomain proteins is not just a historical accident, but a solution to a crucial physics problem in the regulation of gene expression.

q-bio.MN↗

Information processing in living systems

Life depends as much on the flow of information as on the flow of energy. Here we review the many efforts to make this intuition precise. Starting with the building blocks of information theory, we explore examples where it has been possible to measure, directly, the flow of information in biological networks, or more generally where information theoretic ideas have been used to guide the analysis of experiments. Systems of interest range from single molecules (the sequence diversity in families of proteins) to groups of organisms (the distribution of velocities in flocks of birds), and all scales in between. Many of these analyses are motivated by the idea that biological systems may have evolved to optimize the gathering and representation of information, and we review the experimental evidence for this optimization, again across a wide range of scales.

q-bio.QM↗

Entropic forces in a non-equilibrium system: Flocks of birds

When birds come together to form a flock, the distribution of their individual velocities narrows around the mean velocity of the flock. We argue that, in a broad class of models for the joint distribution of positions and velocities, this narrowing generates an entropic force that opposes the cohesion of the flock. The strength of this force depends strongly on the nature of the interactions among birds: if birds are coupled to a fixed number of neighbors, the entropic forces are weak, while if they couple to all other birds within a fixed distance, the entropic forces are sufficient to tear a flock apart. Similar entropic forces should occur in other non-equilibrium systems. For the joint distribution of protein structures and amino-acid sequences, these forces favor the occurrence of "highly designable" structures.

cond-mat.stat-mech↗

Inverse spin glass and related maximum entropy problems

If we have a system of binary variables and we measure the pairwise correlations among these variables, then the least structured or maximum entropy model for their joint distribution is an Ising model with pairwise interactions among the spins. Here we consider inhomogeneous systems in which we constrain (for example) not the full matrix of correlations, but only the distribution from which these correlations are drawn. In this sense, what we have constructed is an inverse spin glass: rather than choosing coupling constants at random from a distribution and calculating correlations, we choose the correlations from a distribution and infer the coupling constants. We argue that such models generate a block structure in the space of couplings, which provides an explicit solution of the inverse problem. This allows us to generate a phase diagram in the space of (measurable) moments of the distribution of correlations. We expect that these ideas will be most useful in building models for systems that are nonequilibrium statistical mechanics problems, such as networks of real neurons.

cond-mat.dis-nn↗

Mapping the stereotyped behaviour of freely-moving fruit flies

Most animals possess the ability to actuate a vast diversity of movements, ostensibly constrained only by morphology and physics. In practice, however, a frequent assumption in behavioral science is that most of an animal's activities can be described in terms of a small set of stereotyped motifs. Here we introduce a method for mapping the behavioral space of organisms, relying only upon the underlying structure of postural movement data to organize and classify behaviors. We find that six different drosophilid species each perform a mix of non-stereotyped actions and over one hundred hierarchically-organized, stereotyped behaviors. Moreover, we use this approach to compare these species' behavioral spaces, systematically identifying subtle behavioral differences between closely-related species.

q-bio.QM↗

Thermodynamics for a network of neurons: Signatures of criticality

The activity of a neural network is defined by patterns of spiking and silence from the individual neurons. Because spikes are (relatively) sparse, patterns of activity with increasing numbers of spikes are less probable, but with more spikes the number of possible patterns increases. This tradeoff between probability and numerosity is mathematically equivalent to the relationship between entropy and energy in statistical physics. We construct this relationship for populations of up to N=160 neurons in a small patch of the vertebrate retina, using a combination of direct and model-based analyses of experiments on the response of this network to naturalistic movies. We see signs of a thermodynamic limit, where the entropy per neuron approaches a smooth function of the energy per neuron as N increases. The form of this function corresponds to the distribution of activity being poised near an unusual kind of critical point. Networks with more or less correlation among neurons would not reach this critical state. We suggest further tests of criticality, and give a brief discussion of its functional significance.

q-bio.NC↗

Morphogenesis at criticality?

Spatial patterns in the early fruit fly embryo emerge from a network of interactions among transcription factors, the gap genes, driven by maternal inputs. Such networks can exhibit many qualitatively different behaviors, separated by critical surfaces. At criticality, we should observe strong correlations in the fluctuations of different genes around their mean expression levels, a slowing of the dynamics along some but not all directions in the space of possible expression levels, correlations of expression fluctuations over long distances in the embryo, and departures from a Gaussian distribution of these fluctuations. Analysis of recent experiments on the gap genes shows that all these signatures are observed, and that the different signatures are related in ways predicted by theory. While there might be other explanations for these individual phenomena, the confluence of evidence suggests that this genetic network is tuned to criticality.

q-bio.MN↗