Noise in gene expression can lead to reversible phenotypic switching. Several experimental studies have shown that the abundance distributions of proteins a population isogenic cells may display multiple distinct maxima. Each these maxima be associated with subpopulation particular phenotype, quantification which is important for understanding cellular decision-making. Here, we devise methodology allows us quantify multimodal and single-cell power spectra regulatory networks. Extending...

Abstract Background It is well known that the deterministic dynamics of biochemical reaction networks can be more easily studied if timescale separation conditions are invoked (the quasi-steady-state assumption). In this case a large network elementary reactions described by smaller effective reactions. Each latter represents group in and has associated with it an macroscopic rate law. A popular method to achieve model reduction presence intrinsic noise consists using laws heuristically...

Normalization of single-cell RNA-sequencing (scRNA-seq) data is a prerequisite to their interpretation. The marked technical variability, high amounts missing observations and batch effect typical scRNA-seq datasets make this task particularly challenging. There need for an efficient unified approach normalization, imputation correction.Here, we introduce bayNorm, novel Bayesian scaling inference counts. method's likelihood function follows binomial model mRNA capture, while priors are...

Growth impacts a range of phenotypic responses. Identifying the sources growth variation and their propagation across cellular machinery can thus unravel mechanisms that underpin cell decisions. We present stochastic model linking gene expression, metabolism replication to predict dynamics in single bacterial cells. Alongside we provide theory analyse chemical reactions coupled with divisions, enabling efficient parameter estimation, sensitivity analysis hypothesis testing. The recovers...

Quantitative mechanistic models are valuable tools for disentangling biochemical pathways and achieving a comprehensive understanding of biological systems. However, to be quantitative the parameters these have estimated from experimental data. In presence significant stochastic fluctuations this is challenging task as simulations usually too time-consuming macroscopic description using reaction rate equations (RREs) no longer accurate. manuscript, we therefore consider moment-closure...

Simulation of biomolecular networks is now indispensable for studying biological systems, from small reaction to large ensembles cells. Here we present a novel approach stochastic simulation embedded in the dynamic environment cell and its surroundings. We thus sample trajectories process described by chemical master equation with time-varying propensities. A comparative analysis shows that existing approaches can either fail dramatically, or else impose impractical computational burdens due...

The PPNCo(CO)4 and BF3·Et2O catalyzed carbonylation of simple functionalized epoxides in DME gives the corresponding β-lactones regioselectively good to high yields. occurred selectively at unsubstituted C−O bond epoxide ring, this reaction tolerates various functional groups such as alkenyl, halide, hydroxy, alkyl ether.

The chemical Fokker-Planck equation and the corresponding Langevin are commonly used approximations of master equation. These equations derived from an uncontrolled, second-order truncation Kramers-Moyal expansion hence their accuracy remains to be clarified. We use system-size show that estimates mean concentrations variance concentration fluctuations about accurate order Ω−3/2 for reaction systems which do not obey detailed balance at least Ω−2 obeying balance, where Ω is characteristic...

Population growth is often ignored when quantifying gene expression levels across clonal cell populations. We develop a framework for obtaining the molecule number distributions in an exponentially growing population taking into account its age structure. In presence of generation time variability, average acquired snapshot does not obey dividing over time, apparently contradicting ergodicity between single cells and population. Instead, we show that variation observed snapshots with known...

How cells maintain their size has been extensively studied under constant conditions. In the wild, however, rarely experience environments. Here, we examine how 24-h circadian clock and environmental cycles modulate cell control division timings in cyanobacterium Synechococcus elongatus using single-cell time-lapse microscopy. Under light, wild-type follow an apparent sizer-like principle. Closer inspection reveals that generates two subpopulations, with born subjective day following...

Cell-to-cell heterogeneity is driven by stochasticity in intracellular reactions and the population dynamics. While these sources are usually studied separately, we develop an agent-based framework that accounts for both factors while tracking every single cell of a growing population. Apart from common intrinsic variability, also predicts extrinsic noise without need to introduce fluctuating rate constants. Instead, fluctuations explained cycle differences age. We provide explicit formulas...

The chemical master equation and the Gillespie algorithm are widely used to model reaction kinetics inside living cells. It is thereby assumed that cell growth division can be modelled through effective dilution reactions extrinsic noise sources. We here re-examine these paradigms developing an analytical agent-based framework of growing dividing cells accompanied by exact simulation algorithm, which allows us quantify dynamics virtually any intracellular network affected stochastic size...

Gene expression is characterized by stochastic bursts of transcription that occur at brief and random periods promoter activity. The kinetics gene burstiness differs across the genome dependent on sequence, among other factors. Single-cell RNA sequencing (scRNA-seq) has made it possible to quantify cell-to-cell variability in a global genome-wide level. However, scRNA-seq data are prone technical variability, including low variable capture efficiency transcripts from individual cells.

It is commonly believed that, whenever timescale separation holds, the predictions of reduced chemical master equations obtained using stochastic quasi-steady-state approximation are in very good agreement with full equations. We use linear noise to obtain a simple formula for relative error between two Michaelis-Menten reaction substrate input. The approach predicted overestimate variance concentration fluctuations by as much 30%. theoretical results validated simulations experimental...

The decision to divide is the most important one that any cell must make. Recent single studies suggest bacteria follow an ``adder'' model of size control, incorporating a fixed amount wall material before dividing. Mycobacteria, including causative agent tuberculosis Mycobacterium tuberculosis, are known asymmetrically resulting in heterogeneity growth rate, doubling time, and other characteristics daughter cells. interplay between asymmetric division adder control have not been extensively...

Abstract Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic proteomic yet it remains unclear if permeates to the metabolic state cell. Here we propose stochastic model show that complex forms heterogeneity emerge from fluctuations enzyme expression catalysis. The analysis predicts clonal populations split into...

Abstract The power control of wind turbines is usually realized via a change in the pitch angle rotor blades. Pitching facilitates exact and reliable deceleration when required. Pitch movements can moreover be used for load control. One these methods called individual (IPC). IPC controls blades individually brings about significant reduction fatigue loads extreme placed on structural components, while at same time reducing yield turbine only slightly. lower reduce material costs, thus, cost...

(R)- and (S)-2-(Acetyloxy)-propanal were prepared [93.8% ee, 102 b/l for (R), 96.9% 149 (S)] via asymmetric hydroformylation of vinyl acetate on a 150−180 g scale used as the starting materials in synthesis chiral isoxazoline imidazole derivatives which proceeded without racemization center.

The linear noise approximation (LNA) offers a simple means by which one can study intrinsic in monostable biochemical networks. Using physical arguments, we have recently introduced the slow-scale LNA (ssLNA) is reduced version of under conditions timescale separation. In this paper, present first rigorous derivation ssLNA using projection operator technique and show that follows uniquely from standard same separation as those required for deterministic quasi-steady state approximation. We...

The accepted stochastic descriptions of biochemical dynamics under well-mixed conditions are given by the Chemical Master Equation and Stochastic Simulation Algorithm, which equivalent. latter is a Monte-Carlo method, which, despite enjoying broad availability in large number existing software packages, computationally expensive due to huge amounts ensemble averaging required for obtaining accurate statistical information. former set coupled differential-difference equations probability...

The linear noise approximation (LNA) is commonly used to predict how regulated and exploited at the cellular level. These predictions are exact for reaction networks composed exclusively of first order reactions or involving bimolecular large numbers molecules. It however well known that gene regulation involves interactions with molecule as small a single copy particular gene. therefore questionable reliable LNA these systems. We implement in software package intrinsic Noise Analyzer (iNA),...

Growth pervades all areas of life from single cells to cell populations tissues. However, size often fluctuates significantly and generation generation. Here we present a unified framework predict the statistics variations within lineage tree proliferating population. We analytically characterise (i) distributions snapshots, (ii) distribution population tree, (iii) lineages across tree. Surprisingly, these differ observing in isolation. In populations, seemingly grow different sizes,...