Biology subjects

Daly, R.

Publications and source records attributed to Daly, R..

17 recordsLinked to original sources

bioRxiv2026

SpiraMed: A Stereotactic Helix-based Therapy Delivery system for the Human Brain

Stereotactic needle-based delivery remains the standard for local administration of Advanced Therapy Medicinal Products (ATMPs) to the human brain. ATMP administration typically involves multiple trajectories, presenting cumulative risks and prolonging surgery. Reflux-prone, patchy therapy coverage compromises clinical results. We demonstrate a novel approach, deploying a helical delivery catheter via a single access trajectory per target, referred to as SpiraMed. Helix retraction is synchronised with therapy delivery, enabling comprehensive target coverage in seconds. Helix pitch and diameter can be precisely tailored to patient-specific target volume and vascular anatomy, as part of the preoperative stereotactic surgical planning process. Testing in agarose phantoms, live sheep and cadaveric human brain confirms enhanced therapy delivery volume, delivery speed and target coverage, with reductions in reflux and predicted risk of bleeding complication. SpiraMed represents a new paradigm, promising to help deliver on the transformative potential of cell and gene therapies across the spectrum of human CNS disease.

bioengineering↗

bioRxiv2026

Cell-type-specific sustained value representations in the claustrum

Flexible decision-making relies on interactions between frontal cortex and subcortical structures. The claustrum, a subcortical nucleus highly interconnected with frontal cortex, influences cortical activity and has been implicated in cognitive functions. Recording from claustrum neurons as mice performed a reinforcement learning task, we found that the activity of almost half of recorded neurons scaled with reward rate and predicted trial- by-trial adjustments in reaction time and choice switching. Individual neurons sustained this activity over seconds between trials. Our recordings identified two electrophysiologically distinct populations. One was excited during task execution and bidirectionally scaled its activity with reward rate. The other was suppressed during task execution, scaled activity inversely with reward rate and projected to frontal cortex, indicating that claustrocortical outputs produce graded increases in activity with decreasing reward rate. Our results identify the claustrum as a subcortical locus for stable value representations and integrate it into neuronal circuits for value-based decision-making.

neuroscience↗

bioRxiv2025

Mapping Risk and Resilience Across Indo-Pacific Reefs with Shark Genomescapes

Overfishing has severely depleted marine populations worldwide, including within protected areas. Illegal and unreported fishing are major contributors to this decline. Large-bodied apex predators such as sharks are among the most affected, with overfishing causing dramatic species declines and ecosystem destabilization due to trophic downgrading. Key barriers to effective marine conservation and management include: Data deficiencies that hinder population benchmarks and impact assessments, limited surveillance, allowing illegal fisheries to disproportionately affect apex predators, and insufficient capacity in vulnerable nations to monitor and protect species within their waters. Our study addresses these challenges through a novel genomic framework that enables assessment of shark population diversity and health, while also improving fisheries traceability by detecting instances of illegal fishing across the Indian and Pacific Oceans. We present the Reefshark Genomescape, the first genome-wide reference database for Indo-Pacific reef sharks, an assessment of genetic diversity, structure, and connectivity of two key species across their Indo-Pacific range and geographic assignment of fished individuals using population-specific genetic signatures. We show that grey reef shark (Carcharhinus amblyrhynchos) populations exhibit high genetic diversity, strong population structure, and elevated Fst values, with previously unknown connectivity between the central and western Indian Ocean and clear isolation of populations in the Andaman Sea. In contrast, silvertip sharks (Carcharhinus albimarginatus) display high connectivity, but show genomic signals of declining population health, supporting a reassessment of their IUCN status. Using supervised machine learning with Monte Carlo cross-validation, we assigned geographic origins to fished grey reef sharks with 96% accuracy. These findings provide critical insights into population structure, connectivity, and health of two ecologically important reef shark species, while establishing a robust method for assigning geographic origin. We anticipate this framework will support regional conservation assessments and targeted management. Moreover, by enabling the identification of fishing hotspots and detection of IUU fishing, it lays the groundwork for a broader traceability system in marine ecosystems. Much like the landmark elephant ivory tracing study, our approach has the potential to transform marine conservation globally. Graphical AbstractWe developed the Reefshark Genomescape, a genomic framework for assessing shark population health and fisheries traceability across the Indo-Pacific. Genome-wide data from grey reef and silvertip sharks revealed contrasting patterns, unexpected connectivity, and genomic signals of decline. Geographic assignment of fished individuals reached 96% accuracy, enabling detection of illegal fishing and identification of hotspots. This framework strengthens regional management, supports IUCN reassessments, and lays the foundation for global marine traceability systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/676358v2_ufig1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@1eafd3aorg.highwire.dtl.DTLVardef@96ebd1org.highwire.dtl.DTLVardef@541d02org.highwire.dtl.DTLVardef@3c9ca2_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2025

Comprehensive LC-MS/MS Data Acquisition in Metabolomics via Maximum Bipartite Matching

BackgroundIn untargeted metabolomics studies, liquid chromatography tandem mass spectrometry (LC-MS/MS) is a powerful analytical platform. The fragmentation spectra produced can be used as "molecular fingerprints" to identify unknown metabolites. However, the high number of analytes that may be co-eluting limits the number of fragmentation spectra that can be collected and potentially identified, presenting a serious bottleneck for many studies. There is a need for new fragmentation strategies which are comprehensive, interpretable and robust, meaning they produce high-quality fragmentation spectra for as many analytes as possible while operating within the constraints of notoriously noisy mass spectrometry data. ResultsWe present a data acquisition workflow which uses a bipartite graph to represent the relationship between opportunities for fragmentation and desired fragmentation targets. This method allows a schedule for data acquisition to be optimally allocated by a standard algorithm. We augment this existing technique by allowing it to solve for multiple samples collectively, allowing it to optimise target intensity (and hence spectral quality) via the use of a weighted matching and by assigning leftover scans redundantly to improve robustness. We also show how this workflow can be used flexibly to generate inclusion windows for Data-Dependent Acquisition (DDA) methods. Our experiments show that several thousand peaks identified in a realistic biological sample can be targeted using only two LC-MS/MS runs. We also further investigate the trade-off between offline workflows and DDA methods by exposing our target list of peaks to realistic variation across samples. We find in those circumstances that our new method has performance (measured by number of peaks targeted comparable to state-of-the-art DDA methods). However, this competitive performance is only possible with our additions to the base maximum matching technique, which provide extra resistance against inter-sample variations. ConclusionsWe have proposed a workflow for LC-MS/MS data acquisition which can be used flexibly for entirely pre-scheduled acquisition or which may generate inclusion windows for online DDA methods. Our results show that the maximum matching workflow with our improvements is state-of-the-art where pre-scheduling is concerned, and in future this foundation may be developed to build more powerful DDA methods which can action the promise of truly comprehensive data acquisition.

bioinformatics↗

bioRxiv2025

Resorbable alginate embolic microsphere for Musculoskeletal embolization applications

Resorbable embolic agents can be used for musculoskeletal (MSK) pain relief applications using a Transarterial Embolisation (TAE) technique. However, inconsistent particle size and shape, degradation rates, and unpredictable resorption and excretion of the breakdown products, limit their widespread clinical adoption. The present study reports self-degradable, rehydratable, freeze-dried, resorbable Ca2+-crosslinked alginate microspheres as a novel vascular embolic agent. The alginate lyase enzyme was incorporated into the alginate microspheres to achieve a controlled degradation rate under physiological conditions. Whilst the feasibility of alginate microspheres as embolic agents has been demonstrated, this is the first study where the controlled release is achieved in physiological conditions. To incorporate the alginate lyase enzyme in the alginate matrix, its activity was reversibly inhibited by preparing an alginate lyase-alginate-excipient mixture in a pH 3.6-3.9 buffered solution. An electrostatic encapsulator enabled the scalable preparation of microspheres of size 210 {+/-} 8 {micro}m at room temperature. The results showed that freeze-dried microspheres regained their shape and size within two minutes after reconstitution with saline, along with active alginate lyase. The reperfusion time of alginate microspheres was evaluated using digital subtraction angiography (DSA) and compared with imipenem and celestine (IMP-CS)in a porcine renal arterial embolisation model. It was observed that most of the blood vessels reperfused within 130-210 minutes, and complete vascular blush was recovered within 24 hours. Embolization with resorbable alginate microspheres induced recoverable ischemic necrosis in the targeted renal arteries. This unique feature of resorbable alginate microspheres in inducing ischemic necrosis, potentially in pain-propagating neovessels, makes it an ideal candidate embolic agent for treating MSK-associated pain using the TAE technique.

bioengineering↗

bioRxiv2023

APOLLO: A genome-scale metabolic reconstruction resource of 247,092 diverse human microbes spanning multiple continents, age groups, and body sites

Computational modelling of microbiome metabolism has proved instrumental to catalyse our understanding of diet-host-microbiome-disease interactions through the interrogation of mechanistic, strain- and molecule-resolved metabolic models. We present APOLLO, a resource of 247,092 human microbial genome-scale metabolic reconstructions spanning 19 phyla and accounting for microbial genomes from 34 countries, all age groups, and five body sites. We explored the metabolic potential of the reconstructed strains and developed a machine learning classifier able to predict with high accuracy the taxonomic strain assignments. We also built 14,451 sample-specific microbial community models, which could be stratified by body site, age, and disease states. Finally, we predicted faecal metabolites enriched or depleted in gut microbiomes of people with Crohns disease, Parkinson disease, and undernourished children. APOLLO is compatible with the human whole-body models, and thus, provide unprecedented opportunities for systems-level modelling of personalised host-microbiome co-metabolism. APOLLO will be freely available under https://www.vmh.life/.

systems biology↗

bioRxiv2023

TopNEXt: Automatic DDA Exclusion Framework for Multi-Sample Mass Spectrometry Experiments

MotivationLiquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) experiments aim to produce high quality fragmentation spectra which can be used to identify metabolites. However, current Data-Dependent Acquisition (DDA) approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input. ResultsWe present TopNEXt, a real-time scan prioritisation framework that improves data acquisition in multi-sample LC-MS/MS metabolomics experiments. TopNEXt extends traditional DDA exclusion methods across multiple samples by using a Region of Interest (RoI) and intensity-based scoring system. Through both simulated and lab experiments we show that methods incorporating these novel concepts acquire fragmentation spectra for an additional 10% of our set of target peaks and with an additional 20% of acquisition intensity. By increasing the quality and quantity of fragmentation spectra, TopNEXt can help improve metabolite identification with a potential impact across a variety of experimental contexts. AvailabilityTopNEXt is implemented as part of the ViMMS framework and the latest version can be found at https://github.com/glasgowcompbio/vimms. A stable version used to produce our results can be found at 10.5281/zenodo.7468914. Data can be found at 10.5525/gla.researchdata.1382. Contactr.mcbride.1@research.gla.ac.uk or vinny.davies@glasgow.ac.uk Supplementary informationSupplementary data are available at Bioarxiv online.

molecular biology↗

bioRxiv2023

Simulated-to-real Benchmarking of Acquisition Methods in Metabolomics

Data-Dependent and Data-Independent Acquisition modes (DDA and DIA, respectively) are both widely used to acquire MS2 spectra in untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolomics analyses. Despite their wide use, little work has been attempted to systematically compare their performance due to the difficulty and cost of performing comparisons with real experimental data due to the lack of ground truth and the costs involved in running large number of acquisitions. Here, we present a systematic in-silico comparison of these two acquisition methods. To do so, we extended our Virtual Metabolomics Mass Spectrometer (ViMMS) framework with a DIA module. Our results show that the performance of these methods varies with the average number of co-eluting ions as the most important factor. At low numbers, DIA outperforms DDA, but at higher numbers, DDA has an advantage as DIA can no longer deal with the large amount of overlapping ion chromatograms. Results from simulation were further validated on an actual mass spectrometer, demonstrating that using ViMMS we can draw conclusions from simulation that translate well into the real world. Embedding this work within ViMMS also allows for researchers to easily simulate DDA and DIA LC-MS/MS runs, validate them on actual instrument, and potentially prototype novel methods that best combine the characteristics of both approaches. We believe that this work provides a useful guide to the choice of DIA or DDA for scientists involved in metabolomics data acquisition.

systems biology↗

bioRxiv2021

PTP1B is an intracellular checkpoint that limits T cell and CAR T cell anti-tumor immunity

Immunotherapies aimed at alleviating the inhibitory constraints on T cells have revolutionised cancer management. To date, these have focused on the blockade of cell surface checkpoints such as PD-1. Herein we identify protein-tyrosine-phosphatase 1B (PTP1B) as an intracellular checkpoint that is upregulated in T cells in tumors. We show that the increased PTP1B limits T cell expansion and cytotoxicity to contribute to tumor growth. T cell-specific PTP1B deletion increased STAT-5 signaling and this enhanced the antigen-induced expansion and cytotoxicity of CD8+ T cells to suppress tumor growth. The pharmacological inhibition of PTP1B recapitulated the T cell-mediated repression of tumor growth and enhanced the response to PD-1 blockade. Furthermore, the deletion or inhibition of PTP1B enhanced the efficacy of adoptively-transferred chimeric-antigen-receptor (CAR) T cells against solid tumors. Our findings identify PTP1B as an intracellular checkpoint whose inhibition can alleviate the inhibitory constraints on T cells and CAR T cells to combat cancer. STATEMENT OF SIGNIFICANCETumors subvert anti-tumor immunity by engaging checkpoints that promote T-cell exhaustion. Here we identify PTP1B as an intracellular checkpoint and therapeutic target. We show that PTP1B is upregulated in intra-tumoral T-cells and that its deletion or inhibition enhances T-cell anti-tumor activity and increases CAR T-cell effectiveness against solid tumors.

cancer biology↗

bioRxiv2021

GraphOmics: an Interactive Platform to Explore and Integrate Multi-Omics Data

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSAn increasing number of studies now produce multiple omics measurements that require using sophisticated computational methods for analysis. While each omics data can be examined separately, jointly integrating multiple omics data allows for a deeper understanding and insights to be gained from the study. In particular data integration can be performed horizontally, where biological entities from multiple omics measurements are mapped to common reactions and pathways. However, data integration remains a challenge due to the complexity of the data and the difficulty in interpreting analysis results. ResultsHere we present GraphOmics, a user-friendly platform to explore, integrate multiple omics datasets and support hypothesis generations. Users can upload transcriptomics, proteomics and metabolomics data to GraphOmics. Relevant entities are connected based on their biochemical relationships, and mapped to reactions and pathways from Reactome. From the Data Browser in GraphOmics, mapped entities and pathways can be ranked, sorted and filtered according to their statistical significance (p-values) and fold changes. Context-sensitive panels provide information on the currently selected entities, while interactive heatmaps and clustering functionalities are also available. As a case study, we demonstrated how GraphOmics was used to interactively explore multi-omics data and support hypothesis generations using two complex datasets from existing Zebrafish regeneration and Covid-19 human studies. ConclusionsGraphOmics is fully open-sourced and freely accessible from https://graphomics.glasgowcompbio.org/. It can be used to integrate multiple omics data horizontally by mapping entities across omics to reactions and pathways. Our demonstration showed that using interactive explorations from GraphOmics, interesting insights and biological hypotheses could be rapidly revealed.

bioinformatics↗

bioRxiv2020

Rapid Development of Improved Data-dependent Acquisition Strategies.

Tandem mass spectrometry (LC-MS/MS) is widely used to identify unknown ions in untargeted metabolomics. Data Dependent Acquisition (DDA) chooses which ions to fragment based upon intensity observed in MS1 survey scans and typically only fragment a small subset of the ions present. Despite this inefficiency, relatively little work has addressed the development of new DDA methods, partly due to the high overhead associated with running the many extracts necessary to optimise approaches in busy MS facilities. In this work, we firstly provide theoretical results that show how much improvement is possible over current DDA strategies. We then describe an in silico framework for fast and cost efficient development of new DDA acquisition strategies using a previously developed Virtual Metabolomics Mass Spectrometer (ViMMS). Additional functionality is added to ViMMS to allow methods to be used both in simulation and on real samples via an instrument application programming interface (API). We demonstrate this framework through the development and optimisation of two new DDA methods which introduce new advanced ion prioritisation strategies. Upon application of the here developed methods to two complex metabolite mixtures, our results show that they are able to fragment more unique ions than standard DDA acquisition strategies.

bioinformatics↗

bioRxiv2020

Cavin3 released from caveolae interacts with BRCA1to regulate the cellular stress response

Caveolae-associated protein 3 (cavin3), a putative tumor suppressor protein, is inactivated in most cancers. We characterized how cavin3 affects the cellular proteome using genome-edited cells together with label-free quantitative proteomics. These studies revealed a prominent role for cavin3 in DNA repair with BRCA1 and BRCA1 A-complex components being downregulated on cavin3 deletion. Cellular and cell-free expression assays, we show a direct interaction between BRCA1 and cavin3. Association of BRCA1 and cavin3 occurs when cavin3 is released from caveolae that are disassembled in response to UV and mechanical stress. Supporting a role in DNA repair, cavin3-deficient cells were sensitized to the effects of PARP inhibition, which compromises DNA repair, and showed reduced recruitment of the BRCA1 A-complex to UV DNA damage foci. Overexpression and RNAi-depletion revealed that cavin3 sensitized various cancer cells to UV-induced apoptosis. We conclude that cavin3 functions together with BRCA1 in multiple pathways that contribute to tumorigenesis.

cancer biology↗

bioRxiv2020

Decomposing metabolite set activity levels with PALS

MotivationRelated metabolites can be grouped into metabolite sets in many ways. Examples of these include the grouping of metabolites through their participation in a series of chemical reactions (forming metabolic pathways); or based on fragmentation spectral similarities and shared chemical substructures. Understanding how such metabolite sets change across samples can be incredibly useful in the interpretation and understanding of complex metabolomics data. However many of the available tools suitable for the enrichment analysis of metabolite sets are based on simple methods that badly handle the missing features inherent in untargeted metabolomics measurements and can be difficult to integrate into existing applications. ResultsWe present PALS (Pathway Activity Level Scoring), a Python library, command-line tool and Web application that performs the ranking of significantly-changing metabolite sets over different experimental conditions. As example applications, PALS is used to analyse metabolites grouped as pathways and by common MS-MS fragmentation structures. A comparison of PALS with two other commonly used methods (ORA and GSEA) is also given, and reveals that PALS is more robust to missing peaks and noisy data than the alternatives. We report results from using PALS to analyse pathways from a study of Human African Trypanosomiasis. Finally, we also report how PALS used tandem MS fragmentation structures to reveal enriched metabolite sets between clades in Rhamnaceae plant data, and on American Gut Project data. AvailabilityPALS is freely available from our project Web site at https://pals.glasgowcompbio.org/. It can be imported as a Python library, run as a stand-alone tool or used as a web application.

bioinformatics↗

bioRxiv2020

Physical and mental health characteristics of adults with subjective cognitive decline: A study of 3,407 people aged 18-81 years from an MTurk-based U.S. national sample

Subjective cognitive decline (SCD), or internal feelings of reduced mental capacity, is of increasing interest in the scientific, clinical, and lay community. Much of the extant literature is focused on SCD as a risk factor for Alzheimers disease in older adults, while less attention has been paid to non-cognitive health correlates of SCD across adulthood. Consequently, we investigated physical and mental health correlates of SCD in younger, middle-aged, and older adults. We recruited 3,407 U.S. residents through Amazons Mechanical Turk, an online labor market. Participants completed a 90-item self-report survey questionnaire assessing sociodemographic characteristics, physical health, sleep, depression, anxiety, loneliness, wisdom, self-efficacy, and happiness. Overall, 493/1930 (25.5%) of younger adults (18-49) and 278/1032 (26.9%) of older adults (50 or older) endorsed the SCD item. Multivariate analysis of variance and follow-up t-tests revealed worse physical and mental health characteristics in people endorsing SCD compared to those who did not, with effect sizes primarily in the medium to large range. Additionally, age did not moderate relationships between SCD and physical and mental health. Results suggest that SCD is associated with a diverse set of negative health characteristics such as poor sleep and high body mass index, and lower levels of positive factors including happiness and wisdom. Effect sizes of psychological correlates of SCD were as large as (or larger than) those of physical correlates, indicating that mental health and affective symptoms may be critical to consider when evaluating SCD. Overall, findings from this large, national U.S. sample suggest the presence of relationships between SCD and multiple psychological and perceived health factors; our results also show that SCD may be highly prevalent in both younger and older adults, suggesting that it be assessed across the adult lifespan.

neuroscience↗

bioRxiv2020

Contributions of the four essential entry glycoproteins to HSV-1 tropism and the selection of entry routes.

Herpes Simplex viruses (HSV-1 and HSV-2) encode up to 16 envelope proteins, four of which are essential for entry. However, whether these four proteins alone are sufficient to dictate the broad cellular tropism of HSV-1 and the selection of different cell-type dependent entry routes is unknown. To begin addressing this, we previously pseudotyped VSV, lacking its native glycoprotein G, with only the four essential entry glycoproteins of HSV-1: gB, gH, gL, and gD. This novel VSV{Delta}G-BHLD pseudotype recapitulated several important features of HSV-1 entry: the requirement for gB, gH, gL, gD, a cellular receptor, and sensitivity to anti-gB and anti-gH/gL neutralizing antibodies. However, due to the use of a single cell type in that study, the tropism of the VSV{Delta}G-BHLD pseudotype was not investigated. Here, we show that the cellular tropism of the pseudotype is severely limited compared to wild-type HSV-1 and that its entry pathways differ from the native HSV-1 entry pathways. To test the hypothesis that other HSV-1 envelope proteins may contribute to HSV-1 tropism, we generated a derivative pseudotype containing the HSV-1 glycoprotein gC (VSV{Delta}G-BHLD-gC) and observed a gC-dependent increase in entry efficiency in two cell types. We propose that the pseudotyping platform developed here has the potential to uncover functional contributions of HSV-1 envelope proteins to entry in a gain-of-function manner. ImportanceHerpes simplex viruses (HSV-1 and HSV-2) contain up to 16 different proteins in their envelopes. Four of these, glycoproteins gB, gD, gH, and gL, are termed essential with regard to entry whereas the rest are typically referred to as non-essential based on the entry phenotypes of the respective single genetic deletions. However, the single-gene deletion approach, which relies on robust loss-of-function phenotypes, may be confounded by functional redundancies among the many HSV-1 envelope proteins. We have developed a pseudotyping platform, in which the essential four entry glycoproteins are isolated from the rest, which can be added back individually for systematic gain-of-function entry experiments. Here, we show the utility of this platform for dissecting the contributions of HSV envelope proteins, both the essential four and the remaining dozen (using gC as an example), to HSV entry.

microbiology↗

bioRxiv2019

In-silico Optimisation of Mass Spectrometry Fragmentation Strategies in Metabolomics

Liquid-Chromatography (LC) coupled to tandem mass spectrometry (MS/MS) is widely used in identifying small molecules in untargeted metabolomics. Various strategies exist to acquire MS/MS fragmentation spectra; however, the development of new acquisition strategies is hampered by the lack of simulators that let researchers prototype, compare, and optimise strategies before validations on real machines. We introduce Virtual Metabolomics Mass Spectrometer (ViMMS), a modular metabolomics LC-MS/MS simulator framework that allows for scan-level control of the MS2 acquisition process in-silico. ViMMS can generate new LC-MS/MS data based on empirical data or virtually re-run a previous LC-MS/MS analysis using pre-existing data in-silico to allow the testing of different fragmentation strategies. It allows the comparison of different fragmentation strategies on real data, with the resulting scan results extractable as mzML files. To demonstrate its utility, we show how our proposed framework can be used to take the output of a real tandem mass spectrometry analysis and examine the effect of varying parameters in Top-N Data Dependent Acquisition protocol. We also demonstrate how ViMMS can be used to compare a recently published Data-set-Dependent Acquisition strategy with a standard Top-N strategy. We expect that ViMMS will save method development time by allowing for offline evaluation of novel fragmentation strategies and optimisation of fragmentation strategy for a particular experiment.

bioinformatics↗

bioRxiv2019

Changing environments and genetic variation: inbreeding does not compromise short-term physiological responses

O_LISelfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce long-term evolutionary potential. However, short-term capacity to respond appropriately to new conditions might not require high levels of standing genetic variation. The purpose of this study was to directly test whether mating system variation and its associated changes in genetic variability in natural populations affected responses to short-term environmental challenges.\nC_LIO_LIWe compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a long-lived perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range.\nC_LIO_LIWe found no effect of mating system on survival or reproductive output, although several phenological traits showed different associations with latitude for outcrossing and inbreeding populations. Natural inbreeding had no effect on the plasticity of physiological responses, using either multivariate approaches or analysis of variation in individual metabolites. Moreover, while both growing environment and time significantly affected the relative abundance of individual metabolites, inbreeding populations responded similarly to outbreeding populations, suggesting adaptation to the outdoor environment, regardless of mating system.\nC_LIO_LIWe conclude that low genetic diversity in naturally inbred populations may not compromise fitness or short-term capacity for appropriate physiological responses to environmental change. The absence of natural costs of inbreeding could help to explain the global success of clonal or asexual mating strategies for adapting to a wide range of environments.\nC_LI

evolutionary biology↗