Population genetic analysis of invasive populations can provide valuable insights into the source of introductions, pathways for expansion, and their demographic histories. Flathead catfish (Pylodictis olivaris) are a prolific invasive species with high fecundity, long-distance dispersal, and piscivorous feeding habits that can lead to declines in native fish populations. In this study, we analyse the genetics of invasive P. olivaris in the Mid-Atlantic region to assess their connectivity and attempt to reconstruct the history of introduced populations. Based on an assessment across 13 microsatellite loci, P. olivaris from the Susquehanna River system (N = 537), Schuylkill River (N = 33), and Delaware River (N = 1) have low genetic diversity (global Hobs = 0.504), although we detected no evidence of substantial inbreeding (FIS = -0.083 to 0.022). P. olivaris from these different river systems were genetically distinct, suggesting separate introductions. However, population structure was much weaker within each river system and exhibited a pattern of high connectivity, with some evidence of isolation by distance. P. olivaris from the Susquehanna and Schuylkill rivers showed evidence for recent genetic bottlenecks, and demographic models were consistent with historical records, which suggest that populations were established by recent founder events consisting of a small number of individuals. Our results show the risk posed by small introductions of P. olivaris, which can spread widely once a population is established, and highlight the importance of prevention and sensitive early detection methods to prevent the spread of P. olivaris in the future.

Single-cell transcriptomics reveals significant variations in transcriptional activity across cells. Yet, it remains challenging to identify mechanisms of transcription dynamics from static snapshots. It is thus still unknown what drives global transcription dynamics in single cells. We present a stochastic model of gene expression with cell size- and cell cycle-dependent rates in growing and dividing cells that harnesses temporal dimensions of single-cell RNA sequencing through metabolic labeling protocols and cel lcycle reporters. We develop a parallel and highly scalable approximate Bayesian computation method that corrects for technical variation and accurately quantifies absolute burst frequency, burst size, and degradation rate along the cell cycle at a transcriptome-wide scale. Using Bayesian model selection, we reveal scaling between transcription rates and cell size and unveil waves of gene regulation across the cell cycle-dependent transcriptome. Our study shows that stochastic modeling of dynamical correlations identifies global mechanisms of transcription regulation. A record of this paper\'s transparent peer review process is included in the supplemental information.

Model parameter estimation is a well-known inverse problem, as long as single-value point data are available as observations of system performance measurement. However, classical statistical methods, such as the minimization of an objective function or maximum likelihood, are no longer straightforward, when measurements are imprecise in nature. Typical examples of the latter include censored data and binary information. Here, we explore Approximate Bayesian Computation as a simple method to perform model parameter estimation with such imprecise information. We demonstrate the method for the example of a plain rainfall-runoff model and illustrate the advantages and shortcomings. Last, we outline the value of Shapley values to determine which type of observation contributes to the parameter estimation and which are of minor importance.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

Surface water nutrient pollution, the primary cause of eutrophication, remains a major environmental concern in Western Lake Erie despite intergovernmental efforts to regulate nutrient sources. The Maumee River Basin has been the largest nutrient contributor. The two primary nutrient sources are inorganic fertilizer and livestock manure applied to croplands, which are later carried to the streams via runoff and soil erosion. Prior studies of nutrient source attribution have focused on large watersheds or counties at annual time scales. Source attribution at finer spatiotemporal scales, which enables more effective nutrient management, remains a substantial challenge. This study aims to address this challenge by developing a generalizable Bayesian network model for phosphorus source attribution at the subwatershed scale (12-digit Hydrologic Unit Code). Since phosphorus release is uncertain, we combine excess phosphorus derived from manure and fertilizer application and crop uptake data, flow information simulated by the SWAT model, and in-stream water quality measurements using Approximate Bayesian Computation to derive a posterior that attributes phosphorus contributions to subwatersheds. Our results show significant variability in subwatershed-scale phosphorus release that is lost in coarse-scale attribution. Phosphorus contributions attributed to the subwatersheds are on average lower than the excess phosphorus estimated by the nutrient balance approach currently adopted by environmental agencies. Fertilizer contributes more soluble reactive phosphorus than manure, while manure contributes most of the unreactive phosphorus. While developed for the specific context of Maumee River Basin, our lightweight and generalizable model framework could be adapted to other regions and pollutants and could help inform targeted environmental regulation and enforcement.

African Swine Fever (ASF) disease transmission parameters are crucial for making response and control decisions when faced with an outbreak, yet they are poorly quantified for smallholder and village contexts within Southeast Asia. Whilst disease-specific factors - such as latent and infectious periods - should remain reasonably consistent, host, environmental and management factors are likely to affect the rate of disease spread. These differences are investigated using Approximate Bayesian Computation with Sequential Monte-Carlo methods to provide disease parameter estimates in four naïve pig populations in villages of Lao People\'s Democratic Republic. The villages represent smallholder pig farmers of the Northern province of Oudomxay and the Southern province of Savannakhet, and the model utilised field mortality data to validate the transmission parameter estimates over the course of multiple model generations. The basic reproductive number between-pigs was estimated to range from 3.08 to 7.80, whilst the latent and infectious periods were consistent with those published in the literature for similar genotypes in the region (4.72 to 6.19 days and 2.63 to 5.50 days, respectively). These findings demonstrate that smallholder village pigs interact similarly to commercial pigs, however the spread of disease may occur slightly slower than in commercial study groups. Furthermore, the findings demonstrated that despite diversity across the study groups, the disease behaved in a consistent manner. This data can be used in disease control programs or for future modelling of ASF in smallholder contexts.

The abnormal aggregation of extracellular amyloid-β(Aβ) in senile plaques resulting in calcium Ca+2 dyshomeostasis is one of the primary symptoms of Alzheimer\'s disease (AD). Significant research efforts have been devoted in the past to better understand the underlying molecular mechanisms driving Aβ deposition and Ca+2 dysregulation. Importantly, synaptic impairments, neuronal loss, and cognitive failure in AD patients are all related to the buildup of intraneuronal Aβ accumulation. Moreover, increasing evidence show a feed-forward loop between Aβ and Ca+2 levels, i.e. Aβ disrupts neuronal Ca+2 levels, which in turn affects the formation of Aβ. To better understand this interaction, we report a novel stochastic model where we analyze the positive feedback loop between Aβ and Ca+2 using ADNI data. A good therapeutic treatment plan for AD requires precise predictions. Stochastic models offer an appropriate framework for modelling AD since AD studies are observational in nature and involve regular patient visits. The etiology of AD may be described as a multi-state disease process using the approximate Bayesian computation method. So, utilizing ADNI data from 2-year visits for AD patients, we employ this method to investigate the interplay between Aβ and Ca+2 levels at various disease development phases. Incorporating the ADNI data in our physics-based Bayesian model, we discovered that a sufficiently large disruption in either Aβ metabolism or intracellular Ca+2 homeostasis causes the relative growth rate in both Ca+2 and Aβ, which corresponds to the development of AD. The imbalance of Ca+2 ions causes Aβ disorders by directly or indirectly affecting a variety of cellular and subcellular processes, and the altered homeostasis may worsen the abnormalities of Ca+2 ion transportation and deposition. This suggests that altering the Ca+2 balance or the balance between Aβ and Ca+2 by chelating them may be able to reduce disorders associated with AD and open up new research possibilities for AD therapy.

The development of mathematical models for studying newly emerging and re-emerging infectious diseases has gained momentum due to global events. The gyrodactylid-fish system, like many host-parasite systems, serves as a valuable resource for ecological, evolutionary, and epidemiological investigations owing to its ease of experimental manipulation and long-term monitoring. Although this system has an existing individual-based model, it falls short in capturing information about species-specific microhabitat preferences and other biological details for different Gyrodactylus strains across diverse fish populations. This current study introduces a new individual-based stochastic simulation model that uses a hybrid τ -leaping algorithm to incorporate this essential data, enhancing our understanding of the complexity of the gyrodactylid-fish system. We compare the infection dynamics of three gyrodactylid strains across three host populations. A modified sequential-type approximate Bayesian computation (ABC) method, based on sequential Monte Carlo and sequential importance sampling, is developed. Additionally, we establish two penalised local-linear regression methods (based on L1 and L2 regularisations) for ABC post-processing analysis to fit our model using existing empirical data. With the support of experimental data and the fitted mathematical model, we address open biological questions for the first time and propose directions for future studies on the gyrodactylid-fish system. The adaptability of the mathematical model extends beyond the gyrodactylid-fish system to other host-parasite systems. Furthermore, the modified ABC methodologies provide efficient calibration for other multi-parameter models characterised by a large set of correlated or independent summary statistics.

Characterizing the processes underlying reproductive isolation between diverging lineages is central to understanding speciation. Here, we present RIDGE-Reproductive Isolation Detection using Genomic polymorphisms-a tool tailored for quantifying gene flow barrier proportion and identifying the relevant genomic regions. RIDGE relies on an Approximate Bayesian Computation with a model-averaging approach to accommodate diverse scenarios of lineage divergence. It captures heterogeneity in effective migration rate along the genome while accounting for variation in linked selection and recombination. The barrier detection test relies on numerous summary statistics to compute a Bayes factor, offering a robust statistical framework that facilitates cross-species comparisons. Simulations revealed RIDGE\'s efficiency in capturing signals of ongoing migration. Model averaging proved particularly valuable in scenarios of high model uncertainty where no migration or migration homogeneity can be wrongly assumed, typically for recent divergence times <0.1 2Ne generations. Applying RIDGE to four published crow data sets, we first validated our tool by identifying a well-known large genomic region associated with mate choice patterns. Second, while we identified a significant overlap of outlier loci using RIDGE and traditional genomic scans, our results suggest that a substantial portion of previously identified outliers are likely false positives. Outlier detection relies on allele differentiation, relative measures of divergence and the count of shared polymorphisms and fixed differences. Our analyses also highlight the value of incorporating multiple summary statistics including our newly developed outlier ones that can be useful in challenging detection conditions.

Fibroblasts in a confluent monolayer are known to adopt elongated morphologies in which cells are oriented parallel to their neighbors. We collected and analyzed new microscopy movies to show that confluent fibroblasts are motile and that neighboring cells often move in anti-parallel directions in a collective motion phenomenon we refer to as \"fluidization\" of the cell population. We used machine learning to perform cell tracking for each movie and then leveraged topological data analysis (TDA) to show that time-varying point-clouds generated by the tracks contain significant topological information content that is driven by fluidization, i.e., the anti-parallel movement of individual neighboring cells and neighboring groups of cells over long distances. We then utilized the TDA summaries extracted from each movie to perform Bayesian parameter estimation for the D\'Orsgona model, an agent-based model (ABM) known to produce a wide array of different patterns, including patterns that are qualitatively similar to fluidization. Although the D\'Orsgona ABM is a phenomenological model that only describes inter-cellular attraction and repulsion, the estimated region of D\'Orsogna model parameter space was consistent across all movies, suggesting that a specific level of inter-cellular repulsion force at close range may be a mechanism that helps drive fluidization patterns in confluent mesenchymal cell populations.