Local Variations Research Articles

Local Variation in Feeding Ground Utilization of Dugongs (Dugong dugon) Across Two Intertidal Seagrass Beds in Talibong Island, Thailand

In this study, we describe the population characteristics and residency patterns of dugongs (Dugong dugon) across two intertidal seagrass beds in Talibong Island, Thailand: Site A, covering an area of 2.0 × 105 m2, and Site B, covering an area of 2.8 × 105 m2. Transect and individual identification surveys were conducted under clear water conditions using drones: 16 separate days over 11 months at Site A and 10 separate days over 3 months at Site B. Sixty-four individuals were identified from 180 videography sessions. The results confirmed at least two distinct patterns of seagrass habitat utilization among sites located approximately 5 km apart. Site A was characterized by a lower population density, higher year-round site fidelity, occupancy by relatively large individuals, and an absence of feeding aggregations. In contrast, Site B was characterized by a higher population density, lower site fidelity, occupancy by individuals with a wider range of body lengths, and the presence of feeding aggregations. The average population density at Site B was three to five times higher than that at Site A. Site A had a median nearest neighbor distance of 320 m with no significant bias in its distribution, whereas Site B had a median of 20 m with a significant bias. The mean site fidelity index for Site A (0.62 ± 0.08; n = 16) was significantly higher than that for Site B (0.39 ± 0.14; n = 10). Dugongs at Site A might have monopolized this site to some extent, while those at Site B might have benefited from increased opportunities for social interaction provided by aggregations. These findings highlight the importance of fine-scale monitoring of feeding ground utilization by dugongs, taking into consideration individual-specific details such as body lengths and resighting rates for a better understanding of their spatial distribution.

Local area variation in health visiting contacts across England for children under age 5: a cross-sectional analysis of administrative data in England 2018-2020

BackgroundThe health visiting service in England leads the government's Healthy Child Programme (HCP) for children under five years. Local authorities and their provider partners deliver this service differently across England. ObjectiveTo describe local authority variation in the delivery of health visiting to children under five years in England (2018-2020). MethodsWe used publicly available statistics on mandated health visiting contacts, and administrative data from the Community Services Dataset (CSDS) on duration, location, and medium of contacts. We mapped population coverage of mandated contacts (new birth visit, 6-8-week review, one-year review, and 2-2½ -year review) and described the frequency and characteristics of mandated and additional contacts across local authorities. ResultsBased on publicly available data, almost all eligible children received their new birth visit, 6-8-week review and one-year review (89%-99%), with substantial variation across local authorities in children receiving he 2-2½ -year review: median 81%, range 33%-98%. Based on CSDS, 80% of local authorities (n=46/57) delivered more additional than mandated contacts: a median of 1.6 additional contacts (range: 0.1-8.5) were delivered for each mandated contact. There was also significant variation in the duration of contacts and the percentage of contacts delivered face-to-face and at home. ConclusionsDespite decreases in funding and workforce since 2015, in 2018--2020, health visiting teams reached nearly all babies and most children face-to-face via mandated contacts, and conducted over one and a half times the number of additional contacts relative to mandated contacts, with variation between local areas. This represents a significant public health infrastructure to support the health and development of babies and children and the wellbeing of their families in the critical period before school. Our study highlights the importance of taking into account additional contacts. Further work is needed to understand variation, including in the way additional contacts are used.

Predictions & perceptions: A social-ecological analysis of human-carnivore conflict in Botswana

Human-carnivore conflict in agrarian landscapes poses a significant threat to both large carnivore populations and human livelihoods. Conservation strategies aimed at mitigating conflict often rely primarily on ecological, landscape-scale factors. However, assessing the influence of microhabitat, as well as local variation in human perceptions, can offer valuable insights into the spatial patterns of human-carnivore conflict. The objectives of this study were to identify landscape predictors of livestock depredation risk, characterize microhabitat vegetation patterns at kill sites, and assess the spatial alignment between ecologically-predicted and human-perceived depredation risk. Through use of predation risk modeling, microhabitat pattern analysis, and participatory mapping exercises, we provide insight into the spatial patterns of livestock depredation risk from a multi-carnivore guild in an agrarian landscape located in the Makgadikgadi region of Botswana. We identified 170 depredation events and conducted 63 participatory mapping exercises across community lands situated between two wildlife protected areas. Results indicated anthropogenic landscape variables as the primary drivers of general depredation risk. Notably, distinct spatial patterns emerged between African lion (Panthera leo) and African wild dog (Lycaon pictus) depredation, underscoring the need for species-specific conservation strategies. Microhabitat analysis indicated a preference for lower vegetation cover within the multi-predator guild, suggesting livestock microhabitat risk-mitigation behaviors outweigh predator hunting strategies. While human perceptions generally aligned with ecologically predicted risk, identified divergences emphasize the importance of tailored conflict mitigation strategies to accommodate varying influences. Overall, the findings advocate for species-specific depredation risk analyses and the inclusion of human perceptions for a comprehensive spatial understanding of livestock depredation risk.

Analytical Study on the Buckling of Cylindrical Shells With Circumferential Thickness Variation Under Varying External Pressure

Abstract In this article, the analytical buckling load coefficient formula for a cylinder with circumferential thickness variation subjected to varying external pressure is established for the first time by developing a quadratic perturbation method. Based on the presented formula, some specific examples that consider either circumferential shell thickness variation or varying lateral pressure are studied and compared with those in the published literature. First, classical cosine thickness variation is analyzed. The computed results of buckling load coefficients indicate that most of differences between the proposed formula and finite element (FE) analyses in previous literature are less than 5%. Second, wind-type pressure load is discussed, and the maximum difference of predicted buckling load coefficients between our formula and results in published article is 2.3%. Third, both circumferential thickness variation and linear liquid pressure are analyzed by the proposed analytical formula and validated by the Galerkin method when both thickness and load variations are small. Therefore, accuracy and reliability of the established formula are validated. For the purpose of engineering application, buckling of a circular shell with local circumferential thickness variation due to weld shrinkage under wind-type pressure is analytically investigated. The effects of thickness variation amplitude, load parameter, half angle of thickness variation, and shell dimensions on buckling load coefficients are studied in detail.

The discourse of ‘falling standards’ of English in Hong Kong

AbstractThe phenomenon of the ‘complaint tradition’, expressing the belief that language standards are deteriorating in some way, has had a long and vibrant existence in discussions of English in Hong Kong. The contribution of a Cultural Linguistics perspective here highlights the nature and significance of the cultural conceptualisations of language, for example, those that are revealed by the use of metaphor. The article begins with an overview of the discourse in Hong Kong, based on a corpus of media articles. The discourse structure and content of the articles, including their metaphorical aspects, are then analysed in more detail. To help understand the persistence of the discourse I draw on the insight that metaphors constitute ‘mini‐narratives’ which construct identities and identity boundaries. The discussion considers how the prevailing conceptualisations of English—some general, and others more culturally specific—serve to reproduce dominant, standardising views and inhibit the acceptance of local variation.

Tip gap effects on film cooling performance of a transonic turbine blade with a distinctive coolant supply arrangement

Considered are the influences of tip gap on film cooling performance variations near to and along the tip or end of a turbine blade with a squealer rim contained within a linear cascade with five airfoils. The film coolant is supplied by two plenums which are positioned at forward and aft locations within the blade. The aft blowing ratio varies between 0.88 and 1.48, the forward blowing ratio is set to be approximately constant in the vicinity of 2.75 to 3.0, and a value of about 1.3 is utilized for the ratio of coolant density relative to the main flow density. Measured results include linearly-averaged and spatially-resolved variations of adiabatic effectiveness, which are presented both for the top portion of the pressure surface and end surface of the blade with the squealer rim. Local effectiveness variations along the top pressure side of the blade show significant effectiveness values downstream of aft pressure side hole outlet locations mostly because film lift-off downstream of these holes is less substantial than observed downstream of the forward holes. Spatially-resolved effectiveness data for the end of the blade with a squealer rim show that the largest values of effectiveness are evident near to and immediately downstream of dusting hole outlet locations. Associated linearly-averaged effectiveness data for the tip of the blade recess region with the 1.2 mm tip gap are as much as about two times higher than values for the 2.0 mm tip gap when compared at each surface location. Local and linearly-averaged surface effectiveness variations for the downstream edge region of the blade squealer tip are most strongly influenced by the film cooling holes which are aft and by the dusting hole which is positioned along the tip of the blade rim near the downstream edge. Here, effectiveness magnitudes are also often higher along the downstream edge rim region with the 1.2 mm tip gap, compared to data associated with the 2.0 mm tip gap.

The last cave lion of the late Upper Palaeolithic: The engraved feline of Grotta Romanelli (southern Italy)

On the occasion of the review of the portable art of Grotta Romanelli, a decorated stone with a feline figure was object of an interdisciplinary study. The analysis considered different approaches so to: characterise the stratigraphic setting of the finding, the rock support, look into the techniques used to decorate the stone, elaborate a graphic documentation (photographs, 3D models and tracings), relate the symbolic production with the environmental context, and consider the motifs into the wider late Upper Palaeolithic (LUP) art production.The work allows confirming that the represented subject corresponds to a Panthera spelaea, and fixing some issues concerning the variability of the decorating activity, which is in line with the graphic tradition of the European LUP. Style and formal variable features of the figure might have responded to specific social conventions or to single author's skills, tracing new investigation lines about the cultural behaviour and the decorating activity: from the collection of the raw material and the preliminary modelling of the support, to the different artistic techniques (engraving and painting), from the use of the object to the definition of possible local artistic variations and/or inspiration at large scale. Moreover, it questions the thematic aspect in relation to the local fauna and its influence in the symbolic production, highlighting the importance of this stone in the wider debate about the extinction of the cave lions. Indeed, the Romanelli lion may represent the last evidence of this animal in Europe.

Among Medicare Beneficiaries, ACA Coverage Expansions Reduced Utilization of Ambulatory Care, Particularly among Duals

Abstract We leverage local area variation in the size of the Affordable Care Act expansions of Medicaid and nongroup coverage and measure changes in Medicare utilization and spending from 2010 through 2018 using the universe of Medicare fee-for-service claims. We find that the ACA coverage expansions led to decreases in the share of Medicare beneficiaries receiving ambulatory care and decreases in spending per beneficiary on ambulatory care. The reductions in ambulatory care were larger among beneficiaries enrolled in both Medicare and Medicaid (“duals”). Our results suggest that coverage expansions may lead to congestion and reduced access to physicians for the continuously insured.

Investigating the Effect of the Separation of Scales in Reduced Order Battery Modelling: Implications on the Validity of the Newman Model

Abstract Modelling lithium-ion battery behaviour is essential for performance prediction and design improvement. However, this task is challenging due to processes spanning many length scales, leading to computationally expensive models. Reduced order models have been developed to address this, assuming a "separation of scales" between micro- and macroscales. This study compares two approaches: direct microstructure-resolved 3D domain electrochemical modelling and a simplified 1D homogenized model, similar to the Doyle-Fuller-Newman model. 

The research investigates the validity of the scale separation assumption in continuum electrode-level models by varying scale separation factors, boundary conditions, and geometries. The findings reveal that in 3D models, more tortuous, less porous microstructures deviate more from 1D predictions, especially under higher discharge rates. However, under realistic conditions, with an electrode featuring eight particles across its thickness and typical transport properties, the 3D model predicts only a slight (2%) increase in current compared to the 1D model at a high rate of 7C (approximately 350 A/m²).

These results suggest that the separation of scales assumption in the DFN model is generally suitable for a wide range of operating conditions. However, 1D models may overlook local variations in electrolyte concentration and potential, crucial for understanding degradation mechanisms.

Partisanship is why people vote in person in a pandemic

AbstractObjectiveThe choice of voting methods has increasingly become a politicized, partisan issue. We ask: Can a nationalized partisan rhetoric cast doubt on vote‐by‐mail (VBM) despite years of experience and a raging pandemic?MethodUsing 2020 general election records in Colorado, an established all‐mail voting state, we analyze first the general choice of voting methods using supervised machine learning and then the choice to switch to in‐person voting despite having used VBM in previous cycles.ResultsThe choice of voting modes is mainly habitual; local variations of COVID‐19 hardly mattered. Republican partisanship played an important role in predicting “switchers” to in‐person voting; the probability was 5.2 percent conditional on being a Republican as opposed to 1.9 percent for a Democrat.ConclusionsThe results suggest that voting in person can be heavily polarized by partisan communication, despite being a health behavior in a pandemic and voters having experience with mail voting.

Carbon stock increase during post-agricultural succession in central France: no change of the superficial soil stock and high variability within forest stages

AbstractForest development following agricultural abandonment concerns extensive areas including the Massif Central region of France where this study was undertaken. This land-use and land-cover change is expected to have effects on biodiversity and ecosystem services, including an increase of carbon sequestration—a major concern in the face of climate change. Nevertheless, uncertainties about carbon stock changes during successions are remaining, especially as to the total stock and the contribution of the different carbon pools. Our work contributes to this field by studying carbon stocks in multiple plots of different successional stages. We measured and estimated carbon stocks in aboveground and belowground vegetation, deadwood, litter and superficial soil, and surveyed plant communities and plot conditions (slope, aspect, soil characteristics). The average total carbon stock increased along the succession from 70.60 at stage 0 to 314.19 tC ha−1 at stage 5. However, the total carbon stocks at the young forest stage (abandoned for 74 years maximum) and the older forest stage (forested for at least 74 years) were not significantly different, and probably reflected strong local heterogeneity in the older forest stage. An increase of the carbon stock was found in all pools, except the soil pool that did not vary significantly between the successional stages. The aboveground carbon stock was found strongly related to the woody species cover, especially the macrophanerophyte cover. This case study supports the view that the succession dynamics of former agricultural plots participates in carbon sequestration, sometimes with great local variations.

North Atlantic Ocean–Originated Multicentennial Oscillation of the AMOC: A Coupled Model Study

Abstract Using a CESM1 control simulation, we conduct a follow-up study to advance our earlier theoretical research on the multicentennial oscillation (MCO) of the Atlantic meridional overturning circulation (AMOC). The modeled AMOC MCO primarily arises from internal oceanic processes in the North Atlantic, potentially representing a North Atlantic Ocean–originated mode of AMOC multicentennial variability (MCV) in reality. Specifically, this AMOC MCO is mainly driven by salinity variation in the subpolar upper North Atlantic, which dominates local density variation. Salinity anomaly in the subpolar upper ocean is enhanced by the well-known positive salinity advection feedback that is realized through anomalous advection in the subtropical to subpolar upper ocean. Meanwhile, mean advection moves salinity anomaly in the subtropical intermediate ocean northward, weakening the subpolar upper salinity anomaly and leading to its phase change. The salinity anomalies have a clear three-dimensional life cycle around the North Atlantic. The mechanism and time scale of the modeled AMOC MCO are consistent with our earlier theoretical studies. In the theoretical model, artificially deactivating either the anomalous or mean advection in the AMOC upper branch prevents it from exhibiting AMOC MCO, underscoring the indispensability of both the anomalous and mean advections in this North Atlantic Ocean–originated AMOC MCO. In our coupled model simulation, the South Atlantic and Southern Oceans do not exhibit variabilities synchronous with the AMOC MCO; the Arctic Ocean’s contribution to the subpolar upper salinity anomaly is much weaker than the North Atlantic. Hence, this North Atlantic Ocean–originated AMOC MCO is distinct from the previously proposed Southern Ocean–originated and Arctic Ocean–originated AMOC MCOs.

Few-shot learning for skin lesion classification: A prototypical networks approach

Prototypical networks (PN) have emerged as one of multiple effective approaches for few-shot learning (FSL), even in medical image classification. This study focuses on implementing a PN for skin lesion classification to assess its performance, generalizability, and robustness when applied across 11 dermoscopic image domains. Unlike conventional FSL scenarios, where the performance is evaluated for unseen classes in the test set, our analysis extends this to evaluate PNs on a complete hold-out dataset with the same classes from a different domain. Differences in a patient’s age, lesion localization, or image acquisition systems variations mimic real-world cross-domain conditions in a clinic. Given the scarcity of medical datasets, this assessment is crucial for potentially translating such systems into real-world clinical settings to support physicians with the diagnosis. Our primary focus is two-fold: investigating whether a PN performs on par with a baseline classifier, even using only a limited number of reference samples from the hold-out test set (in-domain) and whether a PN can generalize to the same classes of unseen domains (cross-domain). Our analysis uncovers that a PN can perform on par with the baseline classifier in an in-domain setting, even with only a few support samples. However, in cross-domain scenarios, a PN exhibits improved performance only on specific domains, while others demonstrate similar or even decreased performance when confronted with a smaller number of images. Our findings contribute to comprehending potential opportunities and limitations of FSL in dermatological practice.

Transient skin friction behavior associated with hemisphere-based vortex ring collisions

Global and local transient skin friction variations resulting from a large-eddy simulation study on ReΓ0=3000 vortex rings colliding with surface-mounted hemispheres of hemisphere-to-vortex-ring diameter-ratios of 0.5≤D/d≤2 are investigated here. Skin friction distribution changes due to the approaching primary vortex ring, formation of secondary/tertiary vortex rings, subsequent mutual interactions between various vortex ring structures, and azimuthal instabilities are clarified with a view to better establish their relationships when the relative hemisphere size varies. Results show that the primary vortex ring produces the highest skin friction levels when it is close to or collides with the hemisphere/flat wall. Additionally, entrainment of wavy secondary/tertiary vortex rings leads to them entangling around the primary vortex ring and resulting in segmented skin friction regions at later stages of the collision process, regardless of the diameter-ratio. Unlike smaller hemispheres, the largest D/d=2 hemisphere here restricts all skin friction changes along its surface with the flat wall unaffected. It is also revealed here that while the diameter-ratio governs the global skin friction distributions, how secondary/tertiary vortex rings interact with the primary vortex ring and how azimuthal instabilities manifest and evolve for all the various vortex rings confer strong influences on the breaking-up and dissipation of regions with high skin friction levels.

FloodNet: Low‐Cost Ultrasonic Sensors for Real‐Time Measurement of Hyperlocal, Street‐Level Floods in New York City

AbstractFlooding is one of the most dangerous and costly natural hazards, and has a large impact on infrastructure, mobility, public health, and safety. Despite the disruptive impacts of flooding and predictions of increased flooding due to climate change, municipalities have little quantitative data available on the occurrence, frequency, or extent of urban floods. To address this, we have been designing, building, and deploying low‐cost, ultrasonic sensors to systematically collect data on the presence, depth, and duration of street‐level floods in New York City (NYC), through a project called FloodNet. FloodNet is a partnership between academic researchers and NYC municipal agencies, working in consultation with residents and community organizations. FloodNet sensors are designed to be compact, rugged, low‐cost, and deployed in a manner that is independent of existing power and network infrastructure. These requirements were implemented to allow deployment of a hyperlocal, city‐wide sensor network, given that urban floods often occur in a distributed manner due to local variations in land development, population density, sewer design, and topology. Thus far, 87 FloodNet sensors have been installed across the five boroughs of NYC. These sensors have recorded flood events caused by high tides, stormwater runoff, storm surge, and extreme precipitation events, illustrating the feasibility of collecting data that can be used by multiple stakeholders for flood resiliency planning and emergency response.

Moving Object Detection in Freely Moving Camera via Global Motion Compensation and Local Spatial Information Fusion.

Motion object detection (MOD) with freely moving cameras is a challenging task in computer vision. To extract moving objects, most studies have focused on the difference in motion features between foreground and background, which works well for dynamic scenes with relatively regular movements and variations. However, abrupt illumination changes and occlusions often occur in real-world scenes, and the camera may also pan, tilt, rotate, and jitter, etc., resulting in local irregular variations and global discontinuities in motion features. Such complex and changing scenes bring great difficulty in detecting moving objects. To solve this problem, this paper proposes a new MOD method that effectively leverages local and global visual information for foreground/background segmentation. Specifically, on the global side, to support a wider range of camera motion, the relative inter-frame transformations are optimized to absolute transformations referenced to intermediate frames in a global form after enriching the inter-frame matching pairs. The global transformation is fine-tuned using the spatial transformer network (STN). On the local side, to address the problem of dynamic background scenes, foreground object detection is optimized by utilizing the pixel differences between the current frame and the local background model, as well as the consistency of local spatial variations. Then, the spatial information is combined using optical flow segmentation methods, enhancing the precision of the object information. The experimental results show that our method achieves a detection accuracy improvement of over 1.5% compared with the state-of-the-art methods on the datasets of CDNET2014, FBMS-59, and CBD. It demonstrates significant effectiveness in challenging scenarios such as shadows, abrupt changes in illumination, camera jitter, occlusion, and moving backgrounds.

Occurrence Characteristics of Nighttime Merged EIA Based on NASA GOLD Observations from 2018 to 2023

The ionosphere equatorial ionization anomaly (EIA) is usually characterized by two plasma density maxima in the Earth’s equatorial region. Merged EIA (MEIA) is a unique phenomenon in the evolution of the EIA. Currently, the occurrence characteristics of MEIA are still not well understood. In this study, we investigate the occurrence characteristics of nighttime MEIA using NASA Global-scale Observations of the Limb and Disk (GOLD) observations between October 2018 and the end of 2023. We found that the occurrence of nighttime MEIA exhibits solar cycle, seasonal, and local time variations. The occurrence rate of the MEIA is inversely dependent on solar activity. Occurrence of the MEIA maximizes near the equinoxes, with a primary (secondary) low occurrence rate near the June (December) solstice. In addition, occurrences of the MEIA are suppressed during the pre-reversal enhancement (PRE), resulting in relatively fewer events. Furthermore, it was found that the occurrence of the MEIA is not significantly dependent on the strength of geomagnetic activity. As far as we know, this study represents the first instance of utilizing observations from GOLD observations to investigate the characteristics of MEIA occurrences and their correlations with solar activity, season, and local time.

Trophic ecology of the greater amberjack in relation to marine environmental characteristics in Taiwanese waters illustrated by stable isotope and stomach content approach

The greater amberjack (Seriola dumerili) holds significant commercially and ecologically important large pelagic marine species in Taiwanese waters. The aim of this study was investigates its stomach contents and stable isotope signatures (δ13C and δ15N) were used to explore the trophic ecology and to detect the dietary variations by length, sex, and season and their associations with marine environmental characteristics. Utilizing a generalized additive model, we elucidate how marine environmental variables influence greater amberjack feeding habitats. Our findings revealed that the mixed layer depth and sea surface temperature explained the highest influence in the greater amberjack feeding ground. To reveal the trophic ecology of the greater amberjack and their ecosystem trophic dynamics, we used an innovative approach combining stomach content analysis (SCA) and stable isotope analysis (SIA) of carbon and nitrogen (δ13C and δ15N) coupled with Bayesian mixing model analysis. By contrast, some of the results in SIA were different from the most important food items identified in SCA; in general, they prefer to consume pelagic prey species. The Bayesian mixing models indicated that the target predator species diet structure was dominated by Trichiuridae and Leiognathidae prey species, as indicated by the highest δ15N values. The relationships of the greater amberjack weight and length were not significant with δ13C values (p > 0.05) but were significant (p < 0.001) with δ15N values. The relationships between trophic positions (TPs) in terms of length, sex, and season suggested an ontogenetic shift, with varied TP values between 4.01 and 5.18, indicating that the greater amberjack is the top-level predator species in the pelagic marine ecosystem. These findings can guide ecosystem-based adaptive fishery management and conservation because the local prey species depletion and variations in marine environmental conditions may affect greater amberjack fisheries in Taiwanese waters.

Imputation of 3D genome structure by genetic–epigenetic interaction modeling in mice

Gene expression is known to be affected by interactions between local genetic variation and DNA accessibility, with the latter organized into three-dimensional chromatin structures. Analyses of these interactions have previously been limited, obscuring their regulatory context, and the extent to which they occur throughout the genome. Here, we undertake a genome-scale analysis of these interactions in a genetically diverse population to systematically identify global genetic–epigenetic interaction, and reveal constraints imposed by chromatin structure. We establish the extent and structure of genotype-by-epigenotype interaction using embryonic stem cells derived from Diversity Outbred mice. This mouse population segregates millions of variants from eight inbred founders, enabling precision genetic mapping with extensive genotypic and phenotypic diversity. With 176 samples profiled for genotype, gene expression, and open chromatin, we used regression modeling to infer genetic–epigenetic interactions on a genome-wide scale. Our results demonstrate that statistical interactions between genetic variants and chromatin accessibility are common throughout the genome. We found that these interactions occur within the local area of the affected gene, and that this locality corresponds to topologically associated domains (TADs). The likelihood of interaction was most strongly defined by the three-dimensional (3D) domain structure rather than linear DNA sequence. We show that stable 3D genome structure is an effective tool to guide searches for regulatory elements and, conversely, that regulatory elements in genetically diverse populations provide a means to infer 3D genome structure. We confirmed this finding with CTCF ChIP-seq that revealed strain-specific binding in the inbred founder mice. In stem cells, open chromatin participating in the most significant regression models demonstrated an enrichment for developmental genes and the TAD-forming CTCF-binding complex, providing an opportunity for statistical inference of shifting TAD boundaries operating during early development. These findings provide evidence that genetic and epigenetic factors operate within the context of 3D chromatin structure.

Imputation of 3D genome structure by genetic-epigenetic interaction modeling in mice.

Gene expression is known to be affected by interactions between local genetic variation and DNA accessibility, with the latter organized into three-dimensional chromatin structures. Analyses of these interactions have previously been limited, obscuring their regulatory context, and the extent to which they occur throughout the genome. Here, we undertake a genome-scale analysis of these interactions in a genetically diverse population to systematically identify global genetic-epigenetic interaction, and reveal constraints imposed by chromatin structure. We establish the extent and structure of genotype-by-epigenotype interaction using embryonic stem cells derived from Diversity Outbred mice. This mouse population segregates millions of variants from eight inbred founders, enabling precision genetic mapping with extensive genotypic and phenotypic diversity. With 176 samples profiled for genotype, gene expression, and open chromatin, we used regression modeling to infer genetic-epigenetic interactions on a genome-wide scale. Our results demonstrate that statistical interactions between genetic variants and chromatin accessibility are common throughout the genome. We found that these interactions occur within the local area of the affected gene, and that this locality corresponds to topologically associated domains (TADs). The likelihood of interaction was most strongly defined by the three-dimensional (3D) domain structure rather than linear DNA sequence. We show that stable 3D genome structure is an effective tool to guide searches for regulatory elements and, conversely, that regulatory elements in genetically diverse populations provide a means to infer 3D genome structure. We confirmed this finding with CTCF ChIP-seq that revealed strain-specific binding in the inbred founder mice. In stem cells, open chromatin participating in the most significant regression models demonstrated an enrichment for developmental genes and the TAD-forming CTCF-binding complex, providing an opportunity for statistical inference of shifting TAD boundaries operating during early development. These findings provide evidence that genetic and epigenetic factors operate within the context of 3D chromatin structure.