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Kaan Öcal

Publications and source records attributed to Kaan Öcal.

6 recordsLinked to original sources

Phase transitions in microbial lineage trees

Microbial populations exhibit high cell-to-cell variability, which fundamentally shapes population behavior. A striking consequence is the existence of phase transitions, where small genetic or environmental changes trigger abrupt shifts in population dynamics. While biological phase transitions have often been proposed, connecting observed behavior to the underlying physics has remained challenging. We combine population genetics with statistical physics to show how phase transitions arise naturally in microbial populations. We highlight the existence of a first-order transition in a model of bacterial plasmid engineering and find a strict lower bound on the number of plasmids that can be stably maintained in a population.

q-bio.PE↗

The Origins of Transient Bimodality

Many dynamical systems exhibit diverse modes of behavior. In biology, such modes can represent individual or cell fates. While the emergence of multimodality is commonly studied, transient bimodality is much less well understood. Under transient bimodality, a system moving from a well-defined initial to a final state transiently undergoes a bifurcation into multiple probability modes. This noise-driven phenomenon can significantly impact processes such as cell differentiation and speciation in the presence of changing environmental conditions. We detail a theoretical approach for understanding transient bimodality connecting results from ecology, optics, chemical reaction networks and cell biology, propose a ``minimal model'' of transient bimodality and derive a general criterion for its presence. We show that fast-to-slow dynamics can lead to transient bimodality in addition to the well-known case of slow-to-fast dynamics. Finally, we discuss the role of transient bimodality across the scientific literature, with emphasis on biochemical kinetics and gene regulation.

q-bio.SC↗

The two-clock problem in population dynamics

Biological time can be measured in two ways: in generations and in physical (chronological) time. When generations overlap, these two notions diverge, which impedes our ability to relate mathematical models to real populations. In this paper we show that nevertheless, the two clocks can be synchronised in the long run via a simple identity relating generational and physical time. This equivalence allows us to directly translate statements from the generational picture to the physical picture and vice versa. We derive a generalized Euler-Lotka equation linking the basic reproduction number $R_0$ to the growth rate, and present a simple identity that relates the selection coefficient of a mutation to the history of typical individuals, with applications to epidemiology, population biology and microbial growth.

q-bio.PE↗

Cell size distributions in lineages

Cells actively regulate their size during the cell cycle to maintain volume homeostasis across generations. While various mathematical models of cell size regulation have been proposed to explain how this is achieved, relating these models to experimentally observed cell size distributions has proved challenging. In this paper we present a simple formula for the cell size distribution in lineages as observed in e.g. a mother machine, and provide a new derivation for the corresponding result in populations, assuming exponential cell growth. Our results are independent of the underlying cell size control mechanism and explain the characteristic shape underlying experimentally observed cell size distributions. We furthermore derive universal moment identities for these distributions, and show that our predictions agree well with experimental measurements of E. coli cells, both on the distribution and the moment level.

q-bio.QM↗

Parameter estimation for biochemical reaction networks using Wasserstein distances

We present a method for estimating parameters in stochastic models of biochemical reaction networks by fitting steady-state distributions using Wasserstein distances. We simulate a reaction network at different parameter settings and train a Gaussian process to learn the Wasserstein distance between observations and the simulator output for all parameters. We then use Bayesian optimization to find parameters minimizing this distance based on the trained Gaussian process. The effectiveness of our method is demonstrated on the three-stage model of gene expression and a genetic feedback loop for which moment-based methods are known to perform poorly. Our method is applicable to any simulator model of stochastic reaction networks, including Brownian Dynamics.

q-bio.QM↗

Flexible statistical inference for mechanistic models of neural dynamics

Mechanistic models of single-neuron dynamics have been extensively studied in computational neuroscience. However, identifying which models can quantitatively reproduce empirically measured data has been challenging. We propose to overcome this limitation by using likelihood-free inference approaches (also known as Approximate Bayesian Computation, ABC) to perform full Bayesian inference on single-neuron models. Our approach builds on recent advances in ABC by learning a neural network which maps features of the observed data to the posterior distribution over parameters. We learn a Bayesian mixture-density network approximating the posterior over multiple rounds of adaptively chosen simulations. Furthermore, we propose an efficient approach for handling missing features and parameter settings for which the simulator fails, as well as a strategy for automatically learning relevant features using recurrent neural networks. On synthetic data, our approach efficiently estimates posterior distributions and recovers ground-truth parameters. On in-vitro recordings of membrane voltages, we recover multivariate posteriors over biophysical parameters, which yield model-predicted voltage traces that accurately match empirical data. Our approach will enable neuroscientists to perform Bayesian inference on complex neuron models without having to design model-specific algorithms, closing the gap between mechanistic and statistical approaches to single-neuron modelling.

stat.ML↗