Biology subjects

Osborne, C.

Publications and source records attributed to Osborne, C..

8 recordsLinked to original sources

bioRxiv2026

EVEE: Interpretable variant effect prediction from genomic foundation model embeddings

Scientific foundation models learn high-dimensional representations from diverse data modalities, yet what they encode and how to extract that knowledge remain open questions. Here we show that probing the internal representations of Evo 2, a 7-billion-parameter genomic foundation model, enables accurate and interpretable genetic variant effect prediction. We introduce a covariance-based probe that captures second-order structure from Evo 2 sequence embeddings to predict variant pathogenicity across variant types and functional consequences, matching or exceeding specialized predictors within their domains. To ground these predictions in known biological mechanisms, we train a complementary panel of probes on existing annotations to detect which genomic properties are disrupted by a variant. This categorized evidence is then integrated with each variants genomic context through a language model to generate variant-specific mechanistic hypotheses. Our pathogenicity predictions correlate with experimental measures of variant function, clinical penetrance, and biobank disease associations while the mechanistic hypotheses are consistent with expert reviews, known mechanism classes, and downstream molecular readouts. We release pathogenicity scores, disruption profiles, and contextualized interpretations for 4.2 million variants from the ClinVar database as an open resource through the Evo Variant Effect Explorer (EVEE). More broadly, this structured probing approach offers a general framework for interrogating foundation models across scientific disciplines and grounding their outputs in existing domain concepts.

genomics↗

bioRxiv2025

VasoTracker 2: An Open-source Platform for Quantitative Analysis of Vascular Reactivity and Function

VasoTracker 2 is an open-source platform for studying blood vessel dynamics, featuring versatile diameter-tracking software and complementary low-cost hardware components. This system surpasses existing tools through accessible, high-resolution analysis across multiple imaging modalities, enabling comprehensive assessment of vascular dynamics in both real-time and pre-recorded experiments. Advanced algorithms enable multi-point diameter tracking in branched vessels, automated pressure-response protocols, and reliable edge detection. The software can assess vessels imaged by brightfield microscopy, fluorescence imaging, and in ultrasound recordings, supporting diverse applications from isolated vessel studies to in vivo assessment. For ex vivo applications, VasoTracker 2 includes modular open-source hardware components that can be used to create a low-cost pressure myograph system: a confocal-compatible vessel chamber and a programmable pressure controller, VasoMoto. By combining powerful analytical capabilities with an open-access approach, VasoTracker 2 provides free software and low-cost hardware alternatives to commercial systems, democratizing access to advanced vascular research tools for scientists worldwide.

physiology↗

bioRxiv2025

Assisted gene flow yields Acropora palmata corals with robust physiological performance under warmer water temperatures in a land-based nursery

Assisted gene flow (AGF) is a conservation approach that facilitates the spread of alleles and may accelerate the recovery of genetically depauperate cohorts. The threatened Caribbean coral Acropora palmata is approaching regional extinction within the western Atlantic partly due to increasing water temperatures associated with global climate change. Previously, AGF was conducted by crossing gametes collected from three regions (Curacao - CU, Florida - FL, and Puerto Rico - PR) characterized by contrasting temperature regimes and low gene flow between them. Here, we tested the thermal tolerance of these AGF cohorts in comparison to purebred Florida and Curacao cohorts. Exposure to high temperatures resulted in few physiological changes, likely because the corals hosted the thermally tolerant algal symbiont, Durusdinium trenchii. However, the FL x FL cohort was the most sensitive to the high temperatures with a significant reduction in net photosynthesis and maximum electron transport rate under this treatment. Like the phenotypic responses, gene expression changes in response to heat stress were muted overall. Consequently, there was little power to detect correlations between genotype and phenotype. Relative to mid-parent values, CUxFL AGF cohorts showed 26 overexpressed and 48 underexpressed genes. Differentially expressed genes included known stress responders. Importantly, hybrid crosses harbored 879 private alleles that were previously not recovered in representative genets from Florida and thus carry important conservation value. These findings suggest that AGF corals not only carry novel alleles but also represent novel gene expression patterns.

ecology↗

bioRxiv2023

Spotty distributions: Spotted Gar (Lepisosteus oculatus) and Spotted Sucker (Minytrema melanops) range expansion in eastern Lake Erie

Natural range expansions in warm-water freshwater fishes are currently not well understood, but shifts in native species distributions can be influenced by many factors, including habitat restoration or degradation and climate change. Here, we provide empirical evidence of range expansions observed in two native freshwater fish species in Lake Erie: the Spotted Gar (Lepisosteus oculatus) and Spotted Sucker (Minytrema melanops). We confirmed our field identifications of L. oculatus and M. melanops using mtDNA barcoding. Maximum likelihood phylogenetic analyses reveal that our samples confidently resolve in the L. oculatus and M. melanops clades respectively, with additional identification support from BLAST searches. Notably, we found no correlation between the increased detection rate of both species and an increase in sampling effort when compared to previous records. Historically, eastern Lake Erie experienced habitat degradation through channelization, siltation, dredging, and toxification of sediments. We hypothesize that recent habitat remediation efforts have provided suitable habitat for both species to recolonize shallow waters with densely vegetated habitat (>90% substrate coverage). Both species are likely to continue their northern expansion as habitats are restored and climatic changes favor warm-water fishes.

zoology↗

bioRxiv2020

Lineage Functional Types (LFTs): Characterizing functional diversity to enhance the representation of ecological behavior in Earth System Models

Process-based vegetation models attempt to represent the wide range of trait variation in biomes by grouping ecologically similar species into plant functional types (PFTs). This approach has been successful in representing many aspects of plant physiology and biophysics, but struggles to capture biogeographic history and ecological dynamics that determine biome boundaries and plant distributions. Grass dominated ecosystems are broadly distributed across all vegetated continents and harbor large functional diversity, yet most Earth System Models (ESMs) summarize grasses into two generic PFTs based primarily on differences between temperate C3 grasses and (sub)tropical C4 grasses. Incorporation of species-level trait variation is an active area of research to enhance the ecological realism of PFTs, which form the basis for vegetation processes and dynamics in ESMs. Using reported measurements, we developed grass functional trait values (physiological, structural, biochemical, anatomical, phenological, and disturbance-related) of dominant lineages to improve ESM representations. Our method is fundamentally different from previous efforts, as it uses phylogenetic relatedness to create lineage-based functional types (LFTs), situated between species-level trait data and PFT-level abstractions, thus providing a realistic representation of functional diversity and opening the door to the development of new vegetation models.

ecology↗

bioRxiv2019

An intergenic non-coding RNA promoter required for histone modifications in the human β-globin chromatin domain

Transcriptome analyses show a surprisingly large proportion of the mammalian genome is transcribed; much more than can be accounted for by genes and introns alone. Most of this transcription is non-coding in nature and arises from intergenic regions, often overlapping known protein-coding genes in sense or antisense orientation. The functional relevance of this widespread transcription is unknown. Here we characterize a promoter responsible for initiation of an intergenic transcript located approximately 3.3 kb and 10.7 kb upstream of the adult-specific human {beta}-globin genes. Mutational analyses in {beta}-YAC transgenic mice show that alteration of intergenic promoter activity results in ablation of H3K4 di- and tri-methylation and H3 hyperacetylation extending over a 30 kb region immediately downstream of the initiation site, containing the adult {delta}- and {beta}-globin genes. This results in dramatically decreased expression of the adult genes through position effect variegation in which the vast majority of definitive erythroid cells harbor inactive adult globin genes. In contrast, expression of the neighboring {varepsilon}- and {gamma}-globin genes is completely normal in embryonic erythroid cells, indicating a developmentally specific variegation of the adult domain. Our results demonstrate a role for intergenic non-coding RNA transcription in the propagation of histone modifications over chromatin domains and epigenetic control of {beta}-like globin gene transcription during development.

genetics↗

bioRxiv2019

Functional diversification enabled grassy biomes to fill global climate space

Global change impacts on the Earth System are typically evaluated using biome classifications based on trees and forests. However, during the Cenozoic, many terrestrial biomes were transformed through the displacement of trees and shrubs by grasses. While grasses comprise 3% of vascular plant species, they are responsible for more than 25% of terrestrial photosynthesis. Critically, grass dominance alters ecosystem dynamics and function by introducing new ecological processes, especially surface fires and grazing. However, the large grassy component of many global biomes is often neglected in their descriptions, thereby ignoring these important ecosystem processes. Furthermore, the functional diversity of grasses in vegetation models is usually reduced to C3 and C4 photosynthetic plant functional types, omitting other relevant traits. Here, we compile available data to determine the global distribution of grassy vegetation and key traits related to grass dominance. Grassy biomes (where > 50% of the ground layer is covered by grasses) occupy almost every part of Earths vegetated climate space, characterising over 40% of the land surface. Major evolutionary lineages of grasses have specialised in different environments, but species from only three grass lineages occupy 88% of the land area of grassy vegetation, segregating along gradients of temperature, rainfall and fire. The environment occupied by each lineage is associated with unique plant trait combinations, including C3 and C4 photosynthesis, maximum plant height, and adaptations to fire and aridity. There is no single global climatic limit where C4 grasses replace C3 grasses. Instead this ecological transition varies biogeographically, with continental disjunctions arising through contrasting evolutionary histories.\n\nSignificance statementWorldviews of vegetation generally focus on trees and forests but grasses characterize the ground layer over 40% of the Earths vegetated land surface. This omission is important because grasses transform surface-atmosphere exchanges, biodiversity and disturbance regimes. We looked beneath the trees to produce the first global map of grass-dominated biomes. Grassy biomes occur in virtually every climate on Earth. However, three lineages of grasses are much more successful than others, characterizing 88% of the land area of grassy biomes. Each of these grass lineages evolved ecological specializations related to aridity, freezing and fire. Recognizing the extent and causes of grass dominance beneath trees is important because grassy vegetation plays vital roles in the dynamics of our biosphere and human wellbeing.

ecology↗

bioRxiv2018

Biochemical mechanisms driving rapid fluxes in C4 photosynthesis

Biochemical mechanisms driving rapid fluxes in C4 photosynthesis Biochemical mechanisms driving... Modeling Plant growth RNA-seq Enzyme measurements Quantum yield measurements Data availability Material and Methods References Sufficient flux through pathways is critical to their function within the metabolic network. A high flux cycle called C4 photosynthesis evolved in some plants to combat the slow speed and low specificity of the plants carbon fixation enzyme Rubisco1. In these plants, flux through the C4 photosynthetic cycle eclipses flux through Rubisco making it the highest flux in planta2,3. Engineering efforts are underway ...

plant biology↗