Biology subjects

Field, D.

Publications and source records attributed to Field, D..

6 recordsLinked to original sources

bioRxiv2026

DUCK-Net: Automated deep learning segmentation of Ductular Reaction in murine liver injury captures multicellular niche dynamics from H&E morphology

Ductular Reactions (DRs) are dynamic and complex multicellular responses that occur as a result of various hepatic injuries. Precise identification and quantification of the extent of DRs is a cornerstone of pre-clinical modelling of liver disease, with links to inflammation, fibrosis, regeneration, and disease severity. Here, we apply a deep learning model, Deep Understanding Convolutional Kernel or DUCK-Net, to the automated detection and segmentation of DRs in whole-slide histopathological images of murine models of liver damage. Following annotation of a training dataset by a specialist liver histopathologist, we demonstrate accelerated performance and accurate detection, achieving a mean Dice coefficient (model-expert segmentation overlap) of 85.4% and a specificity of 98%, indicating minimal false positives. Evaluation of model validity and utility was achieved with a histological time course of cholestatic injury and recovery using 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine diet (DDC) in mice. When assessed against a multiple linear regression model incorporating core epithelial and stromal components of the DR as quantified using IHC, DUCK-Net predicted the spatiotemporal response to injury and repair/resolution with a coefficient of determination (R2) of 0.88. Moreover, DUCK-Net kinetics strongly correlated with published spatial transcriptomic (Stereo-seq) analysis of the DDC model, demonstrating that H&E-based segmentation captures molecular DR dynamics comparable to, or exceeding that of individual IHC markers without the need for immunostaining. DUCK-Net provides a novel and accessible platform for rapid, accurate histological quantification of liver injury reflective of the matrix-rich, multicellular regenerative niche observed in DRs.

cell biology↗

bioRxiv2025

Genealogical analysis of replicate flower colour hybrid zones in Antirrhinum

A major goal of speciation research is identifying loci that underpin barriers to gene flow. Population genomics takes a bottom-up approach, scanning the genome for molecular signatures of processes that drive or maintain divergence. However, interpreting the genomic landscape of speciation is complicated, because genome scans conflate multiple processes, most of which are not informative about gene flow. However, studying replicated population contrasts, including multiple incidences of secondary contact, can strengthen inferences. In this paper, we use linked-read sequencing (haplotagging), FST scans, and genealogical methods to characterise the genomic landscape associated with replicate hybrid zone formation. We studied two flower colour varieties of the common snapdragon, Antirrhinum majus subspecies majus, that form secondary hybrid zones in multiple independent valleys in the Pyrenees. Consistent with past work, we found very low differentiation at one well-studied zone (Planoles). However, at a second zone (Avallenet), we found stronger differentiation and greater heterogeneity, which we argue is due to differences in the amount of introgression following secondary contact. Topology weighting of genealogical trees identified loci where haplotype diversity was associated with the two snapdragon varieties. Two of the strongest associations were at previously identified flower colour loci: Flavia, that affects yellow pigmentation, and Rosea/Eluta, two linked loci that affect magenta pigmentation. Preliminary analysis of coalescence times provides additional evidence for selective sweeps at these loci and barriers to gene flow. Our study highlights the impact of demographic history on the differentiation landscape, emphasizing the need to distinguish between historical divergence and recent introgression.

evolutionary biology↗

bioRxiv2025

Shaping of developmental gradients through selection on multiple loci in Antirrhinum

Development depends on precise shaping of molecular gradients, but how natural selection acts to establish precision is unknown. Here we analyse genes that control differences in the gradient of yellow flower colour between two varieties of snapdragon (Antirrhinum). We show that these differences depend, in part, on cis regulatory variation in the pigment biosynthetic gene, FLAVIA (FLA). FLA interacts multiplicatively with three other loci, one of which is a trans-acting regulator of FLA, to further shape the yellow gradient. All the loci exhibit clines at a hybrid zone, with widths that correlate with phenotypic effect, showing how selection can hone gradient shape with remarkable precision by acting on cis and trans variation at multiple loci.

evolutionary biology↗

bioRxiv2025

Genomic tree scans identify loci underlying adaptive peaks in Antirrhinum

A key question in evolutionary biology is how barriers to gene flow operate and arise between populations, leading to speciation. Barriers are typically identified by comparing populations distinguished by phenotype, geographical location and/or environment. However, such prior classifications may bias recovery towards features obvious to the human eye, influencing mechanistic interpretations. Here we develop a method blind to prior classifications. We apply it to 18 Antirrhinum populations occupying habitats from coastal to alpine. By scanning the genome for regions with deeply rooted similar trees, we identify a single multi-locus partition, comprising less than 0.5% of the genome. It derives from eight genes, three newly identified here, which interact to generate complementary pollinator guides, likely corresponding to two adaptive peaks in a fitness landscape. Hybrid genotypes fall in a fitness valley, allowing the partition to be maintained through hybrid incompatibility and creating steep clines in allele frequency at a hybrid zone. Another partition derives from a single locus linked to a gene controlling plant height. The locus exhibits a shallow cline in allele frequency across an eco-geographic barrier and may be eco-adaptive. Our results suggest that two ancestral subspecies underwent extensive gene flow except at a few barrier loci, showing how both hybrid incompatibility and eco-adaptation can operate to maintain diversity.

evolutionary biology↗

bioRxiv2019

The Biogeography of coelurosaurian theropods and its impact on their evolutionary history

ABSTRACTThe Coelurosauria are a group of mostly feathered theropods that gave rise to birds, the only dinosaurs that survived the Cretaceous-Paleogene extinction event and are still found today. Between their first appearance in the Middle Jurassic up to the end Cretaceous, coelurosaurs were party to dramatic geographic changes on the Earth’s surface, including the breakup of the supercontinent Pangaea, and the formation of the Atlantic Ocean. These plate tectonic events are thought to have caused vicariance or dispersal of coelurosaurian faunas, influencing their evolution. Unfortunately, few coelurosaurian biogeographic hypotheses are supported by quantitative evidence. Here, we report the first, broadly-sampled quantitative analysis of coelurosaurian biogeography using the likelihood-based package BioGeoBEARS. Mesozoic geographic configurations and changes are reconstructed and employed as constraints in this analysis, including their associated uncertainties. We use a comprehensive time-calibrated coelurosaurian evolutionary tree produced from the Theropod Working Group phylogenetic data matrix. Six biogeographic models in the BioGeoBEARS package with different assumptions about the evolution of spatial distribution are tested against the geographic constraints. Our results statistically favour the DIVALIKE+J and DEC+J models, which allow vicariance and founder events, supporting continental vicariance as an important factor in coelurosaurian evolution. Ancestral range estimation indicates frequent dispersal events via the Apulian Route (connecting Europe and Africa during the Early Cretaceous) and the Bering Land Bridge (connecting North America and Asia during the Late Cretaceous). These quantitative results are consistent with commonly inferred Mesozoic dinosaurian dispersals and continental-fragmentation-induced vicariance events. In addition, we recognise the importance of Europe as a dispersal centre and gateway in the Early Cretaceous, as well as other vicariance events like those triggered by the disappearance of land-bridges.View Full Text

paleontology↗

bioRxiv2017

Estimating barriers to gene flow from distorted isolation by distance patterns

In continuous populations with local migration, nearby pairs of individuals have on average more similar genotypes than geographically well separated pairs. A barrier to gene flow distorts this classical pattern of isolation by distance. Genetic similarity is decreased for sample pairs on different sides of the barrier and increased for pairs on the same side near the barrier. Here, we introduce an inference scheme that utilizes this signal to detect and estimate the strength of a linear barrier to gene flow in two-dimensions. We use a diffusion approximation to model the effects of a barrier on the geographical spread of ancestry backwards in time. This approach allows us to calculate the chance of recent coalescence and probability of identity by descent. We introduce an inference scheme that fits these theoretical results to the geographical covariance structure of bialleleic genetic markers. It can estimate the strength of the barrier as well as several demographic parameters. We investigate the power of our inference scheme to detect barriers by applying it to a wide range of simulated data. We also showcase an example application to a Antirrhinum majus (snapdragon) flower color hybrid zone, where we do not detect any signal of a strong genome wide barrier to gene flow.

genetics↗