Biology subjects

Hamilton, J.

Publications and source records attributed to Hamilton, J..

At least 19 recordsLinked to original sources

bioRxiv2026

RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling

Through mitochondrial outer membrane permeabilization (MOMP), mitochondria are central to apoptosis. MOMP is pro-inflammatory, impacting diverse processes including anti-tumor immunity and cellular senescence. Despite this, how damaged mitochondria activate inflammation remains unclear. Recent studies have shown that following MOMP, mitochondria are extensively ubiquitinated activating pro-inflammatory NF-{kappa}B signaling. We identify the E3 ligase, RNF213, as essential for pro-inflammatory mitochondrial ubiquitination following MOMP. RNF213 has an established role in pro- inflammatory, cell-autonomous immunity to bacteria and other pathogens. We discover that RNF213 is required for mitochondrial M1-linked (linear) ubiquitination. Interestingly, this was found to be independent of the canonical M1-ubiquitin ligase complex LUBAC. RNF213 can directly catalyze M1-linked ubiquitination. By promoting mitochondrial M1-linked ubiquitination, RNF213 initiates the recruitment of the essential NF{kappa}B adaptor molecule, NEMO, and subsequently activates pro-inflammatory NF-{kappa}B signaling. Collectively, our findings highlight striking similarities between how cells detect damaged mitochondria and intracellular pathogens, leading to inflammation.

cell biology↗

bioRxiv2026

Genetic variation underlying plasticity in physiological traits mediates response to climate in a Populus hybrid zone

Phenotypic plasticity can buffer the potential fitness consequences of environmental change, yet limited understanding of its genetic basis constrains its application to predicting population response to future climates. Hybrid zones provide powerful systems to study the genetic basis of plasticity because admixture can create novel allele combinations that generate new reaction norms for selection to act upon. Here, we combine two clonally replicated common gardens of Populus trichocarpa x P. balsamifera genotypes with whole-genome resequencing to identify genetic variation underlying plasticity for physiological traits. Admixed genotypes exhibited broader, and in some cases novel, reaction norms relative to parental genotypes, particularly for key stomatal traits. Admixture mapping of genotype-specific reaction norms identified ten candidate genes on chromosome 15, including TWIST, associated with plasticity in adaxial stomatal occurrence and density. Using random forest models, we projected allele-specific responses to climate warming within the hybrid zone to link genetic variation in plasticity with predicted warming. Random forest models forecast that future climates would favor P. trichocarpa alleles at TWIST, while P. balsamifera alleles would be maintained in heterozygous genotypes. These results suggest that hybridization can expand reaction norms and maintain genetic variation that may facilitate rapid phenotypic response needed to adapt to climate change.

evolutionary biology↗

bioRxiv2026

Phenotypic plasticity evolved for climate variability constrains performance under climate warming

Phenotypic plasticity allows plants to rapidly respond to changing environments without the need for evolutionary change or migration. While selection can create variation in plasticity across natural populations, these responses are not adaptive in all environments. To predict whether plasticity will be adaptive requires evaluation of its fitness effects across a range of environments, including novel ones. Here, we test how traits and their plasticity vary for genotypes collected across a natural hybrid zone between two tree species with contrasting climatic niches. Fast-growing Populus trichocarpa inhabits maritime environments with relatively warm and stable temperatures, while P. balsamifera inhabits continental environments with cold winters and large temperature variance throughout the year. We planted 44 clonally replicated genotypes into thirteen common gardens and measured vegetative phenology, leaf morphology, stomata morphology and conductance, and photochemistry. Overall, genotypes from colder, more continental environments exhibited higher plasticity. P. balsamifera ancestry was associated with increased plasticity in timing of fall phenology, stomatal conductance, and leaf mass per unit area. We assessed the effects of trait plasticity on fitness estimated as yearly growth across common gardens and found that the plasticity-fitness relationship was often garden-specific, indicating that the planting environment did not consistently mediate plasticity-fitness relationships. When the effects of trait plasticity on growth varied by garden temperature, higher plasticity generally had neutral or negative associations with growth in warmer environments. These results suggest that elevated plasticity evolved in a P. balsamifera genomic background as part of a climate generalist strategy to seasonal temperature variability, but that there is a trade-off between plasticity and growth in warmer environments. Consequently, less-plastic but warm-adapted P. trichocarpa genotypes are likely to have a fitness advantage under warming climates. These results demonstrate that plasticity may sometimes be maladaptive and will not be universally beneficial in a warming world.

evolutionary biology↗

bioRxiv2026

Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion

Recent genetic studies have shown somatic expansion of the CAG repeat is the key process driving Huntingtons disease (HD) pathogenesis. Recognition of insertion deletion loops (IDLs), lesions prone to form within the CAG repeat, by Muts{beta} (MSH3/MSH2) is thought to be the primary event in the expansion process. This starts a cascade that leads to error prone repair and incorporation of additional CAG units into the repeat. In vitro data shows MSH3 binds IDLs through a DNA binding pocket formed by MSH3 residues Y245/K246. In this study, we investigated the significance of this DNA binding motif in CAG repeat expansion using cell lines harboring long, unstable HTT CAG repeats. Genetic disruption of the MSH3 Y245/K246 motif significantly reduced DNA interaction, exhibited MMR deficiency in a frameshift mutator assay and abrogated repeat expansion in a U2OS cell line expressing mutant HTT exon 1. Pharmacological blockade of this site using a small molecule targeting the DNA binding pocket similarly reduced DNA binding and repeat expansion in a U2OS cell line. Crucially, this molecule also slowed CAG repeat expansion in medium spiny neurons derived from HD patient-iPSCs. Targeting of the MSH3 IDL binding pocket may represent a possible therapeutic strategy.

neuroscience↗

bioRxiv2026

Comparison of Deep Learning Approaches for Extreme Low-SNR Image Restoration

BackgroundLive-cell fluorescence microscopy enables the study of dynamic cellular processes. However, fluorescence microscopy can damage cells and disrupt these dynamic processes through photobleaching and phototoxicity. Reducing light exposure mitigates the effects of photobleaching and phototoxicity but results in low signal-to-noise ratio (SNR) images. Deep learning provides a solution for restoring these low-SNR images. However, these deep learning methods require large, representative datasets for training, testing, and benchmarking, as well as substantial GPU memory, particularly for denoising large images. ResultsWe present a new fluorescence microscopy dataset designed to expand the range of imaging conditions and specimens currently available for evaluating denoising methods. The dataset contains 324 paired high/low-SNR images ranging from four to 282 megapixels across 12 sub-datasets that vary in specimen, objective used, staining type, excitation wavelength, and exposure time. The dataset also includes spinning disk confocal microscopy examples and extreme-noise cases. We evaluated three state-of-the-art deep learning denoising models on the dataset: a supervised transformer-based model, a supervised CNN model, and an unsupervised single image model. We also developed an image stitching method that enables large images to be processed in smaller crops and reconstructed. ConclusionsOur dataset provides a diverse benchmark for evaluating deep learning denoising methods, and our stitching method provides a solution to GPU memory constraints encountered when processing large images. Among the evaluated deep learning models, the supervised transformer-based model had the highest denoising performance but required the longest training time.

bioinformatics↗

bioRxiv2025

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells

Primary human myeloid cells are promising candidates for immunotherapy, yet efficient and scalable technologies for genetic engineering and screening in these cells are limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR genome editing modalities to human monocytes, macrophages, and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoprotein payloads supports gene knockout, base editing and epigenetic silencing, and enables site-specific integration of large DNA sequences when combined with AAV donors for homology-directed repair. Leveraging sgRNA delivery via VPX-lentivirus combined with Cas9 protein delivery via engineered virus-like particle (eVLP) treatment ("SLICeVLP"), we performed the first pooled loss-of-function screens in human macrophages. We uncovered regulators of TNF production and CD80 expression in human macrophages, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation promoted a pro-inflammatory cell state that is resistant to suppressive polarization, and augmented cytotoxicity of engineered HER2 CAR-macrophages. Taken together, this technology platform enables unbiased discovery and characterization of functional gene targets in primary human myeloid cells.

immunology↗

bioRxiv2025

The role of cytonuclear interactions to plant adaptation across a Populus hybrid zone

Co-adaptation of cytoplasmic and nuclear genomes are critical to physiological function for many species. Despite this understanding, hybridization can disrupt co-adaptation leading to a mismatch between maternally-inherited cytoplasmic genomes and biparentally inherited nuclear genomes. Few studies have examined the consequences of cytonuclear interactions to physiological function across environments. Here, we quantify the degree of co-introgression between chloroplast and nuclear-chloroplast (N-cp) genes across repeated hybrid zones and its consequences to physiological function across environments. We use whole-genome resequencing and common garden experiments with clonally replicated genotypes sampled across the natural hybrid zone between Populus trichocarpa and P. balsamifera. We use geographic clines to test for co-introgression of the chloroplast genome with N-cp and non-interacting nuclear genes. Co-introgression of chloroplast and N-cp genes was limited although contact zone-specific patterns suggest that local environments may influence co-introgression. Combining ancestry estimates with phenotypic data across common gardens revealed that mismatches between chloroplast and nuclear ancestry can influence physiological performance, but the strength and direction of these effects vary depending on the environment. Overall, this study highlights the importance of cytonuclear interactions to adaptation, and the role of environment in modifying the effect of those interactions.

evolutionary biology↗

bioRxiv2024

Forecasting hotspots of grassland suitability under climate change for restoration

[bullet] Local species-climate relationships are often considered in restoration management. However, as climate change disrupts species-climate relationships, identifying factors that influence habitat suitability now and into the future for individual species, functional groups, and communities will be increasingly important for restoration. This involves identifying hotspots of community suitability to target seed sourcing and restoration efforts. [bullet]Using ensemble species distribution modeling (eSDM), we analyzed 26 grassland species commonly used in restoration to identify bioclimatic variables influencing their distributions. We predicted habitat suitability under current and future (2050) climates and identified hotspots where diverse species and functional group suitability was greatest. These hotspots of habitat suitability were then overlaid with estimates of landscape connectivity and protected status to quantify potential suitability for restoration now and into the future. [bullet]Temperature and precipitation during warmer quarters largely influenced grassland species habitat suitability. Hotspots of grassland habitat suitability were identified in Minnesota, North Dakota, and South Dakota, with projected northward shifts under future climate scenarios. Overlaying these hotspots with estimates of landscape connectivity and protected status revealed limited connectivity and protection, highlighting regions to prioritize for restoration and conservation efforts. [bullet]Leveraging an understanding of species relationship with climate, this research emphasizes the importance of quantifying connectivity and protected status across aggregated hotspots of species suitability for conservation and restoration. Identifying these hotspots now and into the future can be used to prioritize regions for seed sourcing and restoration, ensuring long-term maintenance of functional ecosystems across grassland communities.

ecology↗

bioRxiv2024

Elevated body mass index in youth is associated with dysregulated surrogate markers of neural inhibition & excitation, and internetwork functional dysconnectivity

The developing child and adolescent brain is thought to have an increased vulnerability to the negative impact of obesity and excessive consumption of hyperpalatable and energy-rich foods. In this study, we investigated the neurophysiological effects of overweight and obesity in 30 participants spanning childhood and adolescence (8-19 years), using a naturalistic viewing paradigm with Inscapes, in a pseudo-resting-state protocol scan with magnetoencephalography (MEG). Subjects were median split on body mass indices (BMI), categorised into two groups comprising: lower <25 kg/m2 (n=15) and higher [≥]25 kg/m2 (n=15). We assessed spontaneous, regional neural function indexed by oscillatory activity, and functional connectivity within and between intrinsic resting brain networks, including the default mode network, dorsal and ventral attention, somatomotor, visual, language, central executive and salience networks. Elevated BMI was associated with significant reductions in activity of the posterior dominant rhythm, and gamma hyperactivity across widespread cortical areas, suggesting intrinsic neuronal hyperexcitability and disinhibition in children and adolescents. Additionally, we observed low-frequency theta hypoconnectivity between resting state networks including the salience, visual, and default mode networks, and overall reduced global efficiency in brain network structure, suggesting reduced effectiveness in neural communication. These findings underscore the neural impact of body composition on the developing brain, suggesting deleterious alterations in excitation and inhibition from surrogate neural markers associated with neurochemistry and brain networks linked with cognitive and behavioural functioning. These alterations may contribute to the persistent behavioural rigidity and difficulties in adopting healthier eating behaviours into adulthood.

neuroscience↗

bioRxiv2024

Genomic signature of reproductive isolation between the last two remnant populations of Torrey pine (Pinus torreyana Parry)

Tree species are often locally adapted to their environments, but the extent to which environmental adaptation contributes to incipient speciation is unclear. One of the rarest pines in the world, Torrey Pine (Pinus torreyana Parry), persists naturally across one island and one mainland population in southern California. The two populations are morphologically and genetically differentiated, but experience some connectivity, making it an ideal system for assessing the evolution of reproductive isolation. Previous work has found evidence of heterosis in F1 mainland-island hybrids, suggesting genetic rescue could be beneficial in the absence of reproductive barriers. Using ddRADseq and GWAS for a common garden experiment of island, mainland, and F1 individuals, we identified candidate loci for environmentally-driven reproductive isolation, their function, and their relationship to fitness proxies. By simulating neutral evolution and admixture between the two populations, we identified loci that exhibited reduced heterozygosity in the F1s, evidence of selection against admixture. SNPs with reduced F1 heterozygosity were enriched for growth and pollination functions, suggesting genetic variants that could be involved in the evolution of reproductive barriers between populations. One locus with reduced F1 heterozygosity exhibited strong associations with growth and reproductive fitness proxies in the common garden, with the mainland allele conferring increased fitness. If this locus experiences divergent selection in the two natural populations, it could promote their reproductive isolation. Finally, although hybridization largely reduced allele fixation in the F1s initially, indicating heterosis is likely due to the masking of deleterious alleles, the emergence of reproductive isolation between populations may diminish the longer-term benefits of genetic rescue in F2 or advanced-generation hybrids. As Torrey pine is a candidate for interpopulation genetic rescue, caution is warranted where longer-term gene flow between diverged populations may result in reduced fitness if barriers have evolved.

genomics↗

bioRxiv2023

Transcriptional acclimation to warming temperatures of the Australian alpine herb Wahlenbergia ceracea

Understanding the molecular mechanisms of heat tolerance could help to predict the impacts of climate change on our native flora. However, much of our current understanding is derived from Arabidopsis thaliana and select crops exposed to short and intense periods of heat stress. Here, we characterise the transcriptomic response of Wahlenbergia ceracea, a perennial herb found in Australias subalpine regions, to sustained moderate warming. We contrasted responses between relatively heat-tolerant and heat-sensitive lines grown under cool (24/15 {o}C day/night) or warm (30/20 {o}C) temperatures. We observed that sustained warming up-regulated genes related to RNA regulation, including modification and splicing, and down-regulated genes associated with photosynthesis and plastid organization. Interestingly, heat-tolerant lines demonstrated a more pronounced repression of photosynthesis-associated genes, compared to heat-sensitive lines, suggesting that the regulation of the light-harvesting machinery may contribute to photosystem thermal tolerance. Co-expression analyses revealed only weak module-level correlations with direct measures of thermal tolerance. However, stronger associations were evident with chlorophyll content and photosynthetic efficiency, which might indirectly influence thermal tolerance. Prediction of transcription factors targeting warming-responsive genes implicated hormone signaling networks, especially ethylene, in contributing to differences in thermal tolerance. In conclusion, we present genomic resources for transcriptome analyses in W. ceracea and highlight the contrasting gene regulatory patterns between relatively heat-tolerant and heat-sensitive W. ceracea lines experiencing sustained moderate warming.

plant biology↗

bioRxiv2023

The impact of gestational diabetes on functional capacity of the infant gut microbiome is modest and transient

Gestational diabetes mellitus (GDM) is a metabolic complication that manifests as hyperglycemia during the later stages of pregnancy. In high resource settings, careful management of GDM limits risk to the pregnancy, and hyperglycemia typically resolves after birth. At the same time, previous studies have revealed that the gut microbiome of infants born to mothers who experienced GDM exhibit reduced diversity and reduction in the abundance of several key taxa, including Lactobacillus. What is not known is what the functional consequences of these changes might be. In this case control study, we applied 16S rRNA sequence surveys and metatranscriptomics to profile the gut microbiome of 30 twelve-month old infants to examine the impact of GDM during pregnancy. Relative to mode of delivery and sex of the infant, maternal GDM status had only a limited impact on the structure and function of the developing microbiome. While GDM samples were associated with a decrease in alpha diversity, we observed no effect on beta diversity and no differentially abundant taxa. Further, while mode of delivery and sex of infant affected the expression of multiple bacterial pathways, most of the impact of GDM status on the function of the infant microbiome appears to be lost by twelve months of age. These data serve to reassure parents and paediatricians that, at least in high resource settings, while mode of delivery appears to impact function and diversity for longer than anticipated, GDM may not have persistent effects on the function nor composition of the infant gut microbiome.

systems biology↗

bioRxiv2023

The impact of patient-specific inlet conditions on oscillatory shear and helicity in haemodynamic simulations of aneurysmal Type-B Aortic Dissection

Type-B Aortic Dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, hemodynamic factors are believed to play a key role. Computational Fluid Dynamics (CFD) and 4D-Flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress, and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (3D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 3D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.

bioengineering↗

bioRxiv2023

Identification of genes associated with abiotic stress tolerance in sweetpotato using weighted gene co-expression network analysis

Sweetpotato, Ipomoea batatas (L.), a key food security crop, is negatively impacted by heat, drought, and salinity stress. We exposed the orange-fleshed cultivar Beauregard to 24 and 48 hours of heat and salt stresses to identify differentially expressed genes (DEGs) in leaves. Analysis revealed both shared and unique sets of up-regulated (650 for heat; 287 for salt) and down-regulated (1,249 for heat; 793 for salt) DEGs suggesting common, yet stress-specific transcriptional responses to these two abiotic stressors. Gene Ontology analysis of downregulated DEGs common to both heat and salt stress revealed enrichment of terms associated with cell population proliferation suggestive of an impact on the cell cycle by the heat stress. To identify shared and unique gene coexpression networks under multiple abiotic stress conditions, weighted gene co-expression network analysis was performed using gene expression profiles from heat, salt, and drought stress treated Beauregard leaves yielding 18 coexpression modules. One module was enriched for response to water deprivation, response to abscisic acid, and nitrate transport indicating synergetic crosstalk between nitrogen, water and phytohormones with genes encoding osmotin, cell expansion, and cell wall modification proteins present as key hub genes in this drought-associated module. This research lays the background for future research in mediating abiotic stress tolerance in sweetpotato.

molecular biology↗

bioRxiv2023

Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination

Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, SARS-CoV-2 immunity has been studied extensively in blood. However, the capacity of peripheral vaccination to generate sustained humoral and cellular immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Bronchoalveolar lavage samples obtained from vaccinated donors with or without prior infection revealed enrichment of spike-specific antibodies, class-switched memory B cells and T cells in the lung mucosa compared to the periphery in the setting of hybrid immunity, whereas in the context of vaccination alone, local anti-viral immunity was limited to antibody responses. Spike-specific T cells persisted in the lung mucosa for up to 5 months post-vaccination and multi-specific T cell responses were detected at least up to 11 months post-infection. Thus, durable lung mucosal immunity against SARS-CoV-2 seen after hybrid exposure cannot be achieved by peripheral vaccination alone, supporting the need for vaccines targeting the airways.

immunology↗

bioRxiv2022

Carcinogen induced expansion of atypical B cells and pre-treatment tumor adjacent tertiary lymphoid structures associate with poor response to BCG in non-muscle invasive bladder cancer

Poor response to Bacillus Calmette-Guerin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle-invasive bladder cancer (NMIBC). Among the multiple factors contributing to poor outcomes, a B cell infiltrated pre-treatment immune microenvironment of NMIBC tumors has emerged as a key determinant of response to BCG. The mechanisms underlying the paradoxical roles of B cells in NMIBC are poorly understood. Here, we show that B cell dominant tertiary lymphoid structures (TLSs), a hallmark feature of chronic mucosal immune response, are abundant and located close to the epithelial compartment in pre-treatment tumors from BCG non-responders. Digital spatial proteomic profiling of whole tumor sections revealed higher expression of immune exhaustion-associated proteins within the TLSs from both responders and non-responders. Chronic local inflammation, induced by the N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen, led to TLS formation with recruitment and differentiation of the immunosuppressive atypical B cell (ABCs) subset within the bladder microenvironment, predominantly in aging female mice compared to their male counterparts. Depletion of ABCs simultaneous to BCG treatment delayed cancer progression in female mice. Our findings provide the first evidence indicating the role of ABCs in BCG response and will inform future development of therapies targeting the B cell exhaustion axis.

cancer biology↗

bioRxiv2022

Transcriptional signatures of wheat inflorescence development

In order to maintain global food security, it will be necessary to increase yields of the cereal crops that provide most of the calories and protein for the worlds population, which includes common wheat (Triticum aestivum L.). An important factor contributing to wheat yield is the number of grain-holding spikelets which form on the spike during inflorescence development. Characterizing the gene regulatory networks controlling the timing and rate of inflorescence development will facilitate the selection of natural and induced gene variants that contribute to increased spikelet number and yield. In the current study, co-expression and gene regulatory networks were assembled from a temporal wheat spike transcriptome dataset, revealing the dynamic expression profiles associated with the progression from vegetative meristem to terminal spikelet formation. Consensus co-expression networks revealed enrichment of several transcription factor families at specific developmental stages including the sequential activation of different classes of MIKC-MADS box genes. This gene regulatory network highlighted interactions among a small number of regulatory hub genes active during terminal spikelet formation. Finally, the CLAVATA and WUSCHEL gene families were investigated, revealing potential roles for TaCLE13, TaWOX2, and TaWOX7 in wheat meristem development. The hypotheses generated from these datasets and networks further our understanding of wheat inflorescence development.

plant biology↗

bioRxiv2022

Genome-wide association and genomic prediction of growth traits in the European flat oyster (Ostrea edulis)

The European flat oyster (Ostrea edulis) is a bivalve mollusc that was once widely distributed in Europe and represented an important food resource for humans for centuries. Populations of O. edulis experienced a severe decline across their biogeographic range mainly due to anthropogenic activities and disease outbreaks. To restore the economic and ecological benefits of European flat oyster populations, extensive protection and restoration efforts are in place within Europe. In line with the increasing interest in supporting restoration and oyster farming through the breeding of stocks with enhanced performance, the present study aimed to evaluate the potential of genomic selection for improving growth traits in a European flat oyster population obtained from successive mass-spawning events. Four growth-related traits were evaluated: total weight (TW), shell height (SH), shell width (SW) and shell length (SL). The heritability of the growth traits was moderate-low, with estimates of 0.45, 0.37, 0.22, and 0.32 for TW, SH, SW and SL, respectively. A genome-wide association analysis revealed a largely polygenic genetic architecture for the four growth traits, with two distinct QTLs detected on chromosome 4. To investigate whether genomic selection can be implemented in flat oyster breeding at a reduced cost, the utility of low-density SNP panels (down to 100 SNPs) was assessed. Genomic prediction accuracies using the full density panel were high (>0.83 for all traits). The evaluation of the effect of reducing the number of markers used to predict genomic breeding values revealed that similar selection accuracies could be achieved for all traits with 2K SNPs as for a full panel containing 4,577 SNPs. Only slight reductions in accuracies were observed at the lowest SNP density tested (i.e. 100 SNPs), likely due to a high relatedness between individuals being included in the training and validation sets during cross-validation. Overall, our results suggest that the genetic improvement of growth traits in oysters is feasible. Nevertheless, and although low-density SNP panels appear as a promising strategy for applying GS at a reduced cost, additional populations with different degrees of genetic relationship should be assessed to derive estimates of prediction accuracies to be expected in practical breeding programmes.

genetics↗