"Anti-Windup Protection Circuits for Biomolecular Integral Controllers", bioRxaiv. (2023) will be discussed in this Journal Club. In this study, we obtain an exact time-dependent solution of the chemical master equation (CME) of an extension of the two-state telegraph model describing bursty or non-bursty protein expression in the presence of positive or negative autoregulation. Using the method of spectral decomposition, we show that the eigenfunctions of the generating function solution of the CME are Heun functions, while the eigenvalues can be determined by solving a continued fraction equation. Our solution generalizes and corrects a previous time-dependent solution for the CME of a gene circuit describing non-bursty protein expression in the presence of negative autoregulation [Ramos et al., Phys. Rev. E 83, 062902 (2011)]. In particular, we clarify that the eigenvalues are generally not real as previously claimed. We also investigate the relationship between different types of dynamic behavior and the type of feedback, the protein burst size, and the gene switching rate. If you want to participate in the seminar, you need to enter IBS builiding (https://www.ibs.re.kr/bimag/visiting/). Please contact if you first come IBS to get permission to enter IBS building.

Let $\mathcal{G}$ and $\mathcal{H}$ be minor-closed graphs classes. The class $\mathcal{H}$ has the Erdős-Pósa property in $\mathcal{G}$ if there is a function $f : \mathbb{N} \to \mathbb{N}$ such that every graph $G$ in $\mathcal{G}$ either contains (a packing of) $k$ disjoint copies of some subgraph minimal graph $H \not\in \mathcal{H}$ or contains (a covering of) $f(k)$ vertices, whose removal creates a graph in $\mathcal{H}$. A class $\mathcal{G}$ is a minimal EP-counterexample for $\mathcal{H}$ if $\mathcal{H}$ does not have the Erdős-Pósa property in $\mathcal{G}$, however it does have this property for every minor-closed graph class that is properly contained in $\mathcal{G}$. The set $\frak{C}_{\mathcal{H}}$ of the subset-minimal EP-counterexamples, for every $\mathcal{H}$, can be seen as a way to consider all possible Erdős-Pósa dualities that can be proven for minor-closed classes. We prove that, for every $\mathcal{H}$, $\frak{C}_{\mathcal{H}}$ is finite and we give a complete characterization of it. In particular, we prove that $|\frak{C}_{\mathcal{H}}| = 2^{\operatorname{poly}(\ell(h))}$, where $h$ is the maximum size of a minor-obstruction of $\mathcal{H}$ and $\ell(\cdot)$ is the unique linkage function. As a corollary of this, we obtain a constructive proof of Thomas' conjecture claiming that every minor-closed graph class has the half-integral Erdős-Pósa property in all graphs. This is joint work with Christophe Paul, Dimitrios Thilikos, and Sebastian Wiederrecht.

“Transcriptome-wide analysis of cell cycle-dependent bursty gene expression from single-cell RNA-seq data using mechanistic model-based inference”, bioRxiv (2024) will be discussed in this Journal Club. Bursty gene expression is quantified by two intuitive parameters: the burst frequency and the burst size. While these parameters are known to be cell-cycle dependent for some genes, a transcriptome-wide picture remains missing. Here we address this question by fitting a suite of mechanistic models of gene expression to mRNA count data for thousands of mouse genes, obtained by sequencing of single cells for which the cell-cycle position has been inferred using a deep-learning approach. This leads to the estimation of the burst frequency and size per allele in the G1 and G2/M cell-cycle phases, hence providing insight into the global patterns of transcriptional regulation. In particular, we identify an interesting balancing mechanism: on average, upon DNA replication, the burst frequency decreases by ≈ 50%, while the burst size increases by the same amount. We also show that for accurate estimation of the ratio of burst parameters in the G1 and G2/M phases, mechanistic models must explicitly account for gene copy number differences between cells but, surprisingly, additional corrections for extrinsic noise due to the coupling of transcription to cell age within the cell cycle or technical noise due to imperfect capture of RNA molecules in sequencing experiments are unnecessary. If you want to participate in the seminar, you need to enter IBS builiding (https://www.ibs.re.kr/bimag/visiting/). Please contact if you first come IBS to get permission to enter IBS building.

"Reduced model for female endocrine dynamics: Validation and functional variations", Mathematical Biosciences (2023) will be discussed in this Journal Club. A normally functioning menstrual cycle requires significant crosstalk between hormones originating in ovarian and brain tissues. Reproductive hormone dysregulation may cause abnormal function and sometimes infertility. The inherent complexity in this endocrine system is a challenge to identifying mechanisms of cycle disruption, particularly given the large number of unknown parameters in existing mathematical models. We develop a new endocrine model to limit model complexity and use simulated distributions of unknown parameters for model analysis. By employing a comprehensive model evaluation, we identify a collection of mechanisms that differentiate normal and abnormal phenotypes. We also discover an intermediate phenotype—displaying relatively normal hormone levels and cycle dynamics—that is grouped statistically with the irregular phenotype. Results provide insight into how clinical symptoms associated with ovulatory disruption may not be detected through hormone measurements alone. If you want to participate in the seminar, you need to enter IBS builiding (https://www.ibs.re.kr/bimag/visiting/). Please contact if you first come IBS to get permission to enter IBS building.

We prove a conjecture of Bonamy, Bousquet, Pilipczuk, Rzążewski, Thomassé, and Walczak, that for every graph $H$, there is a polynomial $p$ such that for every positive integer $s$, every graph of average degree at least $p(s)$ contains either $K_{s,s}$ as a subgraph or contains an induced subdivision of $H$. This improves upon a result of Kühn and Osthus from 2004 who proved it for graphs whose average degree is at least triply exponential in $s$ and a recent result of Du, Girão, Hunter, McCarty and Scott for graphs with average degree at least singly exponential in $s$. As an application, we prove that the class of graphs that do not contain an induced subdivision of $K_{s,t}$ is polynomially $\chi$-bounded. In the case of $K_{2,3}$, this is the class of theta-free graphs, and answers a question of Davies. Along the way, we also answer a recent question of McCarty, by showing that if $\mathcal{G}$ is a hereditary class of graphs for which there is a polynomial $p$ such that every bipartite $K_{s,s}$-free graph in $\mathcal{G}$ has average degree at most $p(s)$, then more generally, there is a polynomial $p'$ such that every $K_{s,s}$-free graph in $\mathcal{G}$ has average degree at most $p'(s)$. Our main new tool is an induced variant of the Kővári-Sós-Turán theorem, which we find to be of independent interest. This is joint work with Romain Bourneuf (ENS de Lyon), Matija Bucić (Princeton), and James Davies (Cambridge),

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ZOOM ID: 997 8258 4700(pw: 1234)

There has been a raising interest on the study of perfect matchings in uniform hypergraphs in the past two decades, including extremal problems and their algorithmic versions. I will introduce the problems and some recent developments.

We prove the existence of a computable function $f\colon\mathbb{N}\to\mathbb{N}$ such that for every integer $k$ and every digraph $D$ either contains a collection $\mathcal{C}$ of $k$ directed cycles of even length such that no vertex of $D$ belongs to more than four cycles in $\mathcal{C}$, or there exists a set $S\subseteq V(D)$ of size at most $f(k)$ such that $D-S$ has no directed cycle of even length. This is joint work with Maximilian Gorsky, Ken-ichi Kawarabayashi, and Stephan Kreutzer.

The uniform Turán density $\pi_u(F)$ of a hypergraph $F$, introduced by Erdős and Sós, is the smallest value of $d$ such that any hypergraph $H$ where all linear-sized subsets of vertices of $H$ have density greater than $d$ contains $F$ as a subgraph. Over the past few years the value of $\pi_u(F)$ was determined for several classes of 3-graphs, but no nonzero value of $\pi_u(F)$ has been found for $r$-graphs with $r>3$. In this talk we show the existence of $r$-graphs $F$ with $\pi_u(F)={r \choose 2}^{-{r \choose 2}}$, which we conjecture is minimum possible. Joint work with Frederik Garbe, Daniel Il’kovic, Dan Král’ and Filip Kučerák.

Cell-to-cell variability in gene expression exists even in a homogeneous population of cells. Dissecting such cellular heterogeneity within a biological system is a prerequisite for understanding how a biological system is developed, homeostatically regulated, and responds to external perturbations. Single-cell RNA sequencing (scRNA-seq) allows the quantitative and unbiased characterization of cellular heterogeneity by providing genome-wide molecular profiles from tens of thousands of individual cells. Single-cell sequencing is expanding to combine genomic, epigenomic, and transcriptomic features with environmental cues from the same single cell. In this talk, I demonstrate how scRNA-seq can be applied to dissect cellular heterogeneity and plasticity of adipose tissue, and discuss related computational challenges.