Biology subjects

Lecomte, N.

Publications and source records attributed to Lecomte, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Neoantigen-reactive CD8+ T cell engagement marks exceptional survivors of pancreatic cancer

Pancreatic cancer (PC) is largely refractory to immune checkpoint blockade (ICB), although homologous recombination-deficient (HRD) tumors may derive benefit. In the POLAR trial of maintenance pembrolizumab plus olaparib after platinum-based chemotherapy for metastatic PC, responses remained heterogeneous. To define determinants of productive antitumor immunity, we integrated longitudinal blood TCR sequencing with tumor single-cell and spatial profiling. Durable benefit was associated with rare tumor-infiltrating, peripherally expanding (TIE) CD8+ T cell clonotypes, a subset of which were functionally neoantigen-reactive. TIE patients showed markedly prolonged survival beyond established genomic and immune biomarkers. Conversely, resistance was associated with spatial T cell exclusion, myCAF-rich stromal remodeling, basal-like/KRAS-associated malignant-cell programs, and expansion of CTLA4 regulatory T cells linked to local immunosuppressive remodeling. These findings define a clonotype-resolved framework for immune monitoring and identify complementary stromal, tumor-intrinsic, and regulatory immune barriers that may guide rational combination immunotherapy in PC.

cancer biology↗

bioRxiv2026

POLQ-driven repair scars shape the immunogenic landscape of homologous recombination-deficient pancreatic cancer

Pancreatic cancer (PC) is broadly resistant to immune checkpoint blockade, although a subset of homologous recombination-deficient (HRD) tumors exhibits durable immune engagement. The genomic features that distinguish these immune-responsive tumors from immune-inert HRD tumors remain poorly understood. Here we identify a microhomology-mediated end joining (MMEJ) repair scar, the MMEJ Deletion Footprint (MDF), as a genomic readout of POLQ-associated error-prone repair that enriches for frameshift indels. Across the multi-omic discovery cohort integrating tumor genomics, single-nucleus transcriptomics and spatial immune profiling, MDF-high HRD PC exhibited increased frameshift-indel-derived neoantigens and interferon programs. MDF was further associated with remodeling of the myeloid compartment toward MHC II-high dendritic cell-like antigen-presenting macrophage states and the immune synapse architecture marked by increased spatial interaction between APC-like macrophages and cytotoxic CD8+ T cells. These tissue-level features aligned with a functional trajectory shift of CD8+ T cells, consistent with effective anti-tumor immunity and was associated with favorable clinical outcomes of patients. Together, our findings position MMEJ-linked repair scarring as actionable biology that connects an HRD genotype to immune organization and suggests rational immunotherapy combinations that may enhance antigen presentation and myeloid activation to extend durable benefit in HRD-lineage cancers.

cancer biology↗

bioRxiv2025

Multiannual environmental forcing shapes breeding phenology and success in a subantarctic seabird

Climate-driven phenological mismatches threaten avian reproduction by disrupting food availability during critical breeding stages. In marine ecosystems, time lags between environmental changes and their effects on food webs are challenging to model, yet they can have a profound impact on top-predator reproduction. We disentangle how oceanic and climatic variability influence the breeding phenology and success of a keystone seabird of the Southern Ocean drawing on 24 years of data from 17,000 marked king penguins. We document an exceptional 19-day advancement in breeding phenology, alongside increased breeding success (44% in 2000, 62% in 2023). A sliding-window analysis reveals that sea temperature and primary production in key foraging zones predict both phenology and breeding success, with lags ranging from several weeks to two years. While king penguins appear to be keeping pace with current changes, their dependence on multi-year environmental conditions underscores the vulnerability of top predators to unpredictable, fast-changing, and more frequent extreme conditions.

ecology↗

bioRxiv2025

Flexible foraging effort shapes Adelie penguin reproductive success across Antarctica and sea ice conditions

Understanding how species deal with diverse environmental conditions is crucial for predicting their future responses to climate change. In Antarctica, changing sea ice dynamics threaten ice-dependent species. Whilebehavioural adjustmentscould help mitigate these threats, their effectiveness under future environmental conditions and potential thresholds remain unclear. Long-term studies and circumpolar approaches could address this challenge. Our 15-year study (2010-2024) of over 23,000 foraging trips from Adelie penguins (Pygoscelis adeliae) in East Antarctica, identified a non-linear relationship between sea ice concentration (SIC) and foraging effort when landfast ice was absent, a situation anticipated to define the species future habitat during chick-rearing. Minimal effort occurred at 10-20% SIC, but more than doubled with the presence of landfast ice or heavy pack-ice, with females showing greater sensitivity to these ice changes. Acircumpolar analysis of similar data demonstrated that foraging effort during chick-guarding predicted reproductive success across ten Adelie penguin populations. Reproductive success remained high until foraging trips exceeded approximately 29 hours, after which performance declined sharply. This indicates that while behavioural flexibility can buffer against moderate environmental changes, it has clear limits. Our findings establish foraging trip duration as a valuable early warning indicator for population responses to environmental change.

ecology↗

bioRxiv2024

Source amplitude increases with body mass across avian genera

Amplitude, or intensity, of sound is a fundamental characteristic of inter acoustic communication, with relevance in many scientific fields. The amplitude of an animals acoustic signal at its source ("source amplitude") may be particularly relevant in the field of acoustic allometry, where relationships between species physical and acoustic features (e.g., dominant frequency) have been well-established across taxa. However, despite their potential scientific value, records and studies of source amplitudes remain remarkably scarce for avian species. Here we present novel estimates of source amplitude (range, mean, and median) for 17 species of Arctic-breeding birds, derived from measurements made in Utqia[g]vik, Alaska during June 2024. We found a strong positive correlation between body mass and source amplitude in this data via a Markov Chain Monte Carlo multivariate generalized linear mixed model (MCMCglmm). Both phylogeny and individual identity were important random effects in this model. In contrast, random effects from environmental factors and measurement characteristics were minimal. Our work represents the first model describing the relationship between source amplitude and allometry across avian genera. We hope that this study will spur other investigations into avian source amplitude and its relationship to morphological and life history features for species in the Arctic and elsewhere.

ecology↗

bioRxiv2024

Declining juvenile survival of Adelie penguins in Antarctica

As summer sea ice around Antarctica reaches modern lows, quantifying the demographic response of polar species to such environmental changes becomes critical. To achieve this, synthesizing results across species ranges and elucidating the environmental factors driving population dynamics are key. Adelie penguins are considered reliable indicators of changes in Antarctica but the processes through which sea ice and other environmental factors shape their population dynamics are still unclear, especially for critical age groups such as juveniles. Using a 17-year dataset of Adelie penguins electronically tagged in Adelie Land (Antarctica), we found that juvenile survival probability was most impacted by sea ice concentration near their natal colony right after fledging, with lower ice concentrations detrimental to survival. Importantly, we found that juvenile survival declined by 32% from 2007 to 2020, mirroring trends at other distant colonies. The emergence of similar patterns at opposite ends of the continent may be an early signal for shifts in population trends expected from climate change.

ecology↗

bioRxiv2024

Genomic evolution of pancreatic cancer at single-cell resolution

We adapted a previously developed targeted single-nucleus DNA sequencing (snDNA-seq) method and constructed a new suite of computational analysis tools to study 137,491 single-nucleus DNA libraries from 24 pancreatic cancers collected under a variety of clinical scenarios including early and late diagnoses, different metastatic sites and before- and after-treatment. We refined the mutational landscape of pancreatic cancer by capturing events missed by bulk sequencing, and validated the evolution pattern of early fixation of driver single-nucleotide variants (SNVs) followed by generation of intratumoral heterogeneity for copy number variations (CNVs). Intertumoral convergent evolution was common, including subclonal inactivation of TGF-{beta} pathway by mutating various components of it; intratumoral convergence was rarely observed, likely due to strong selective force in pancreatic cancer development. Continuous evolution was frequently seen manifesting as CNVs. In the context of non-targeted treatments, no particular pattern was found across metastases or through treatment. In six pancreatic cancers with germline BRCA2 mutation, we discovered varied timing of biallelic inactivation of BRCA2, which sculpted different evolutionary trajectories and could presumably contribute to differential response to treatment. As the first large-scale application of targeted snDNA-seq on pancreatic cancer, this work provides a sample processing and computational analysis pipeline that warrants further clinical utility.

cancer biology↗

bioRxiv2024

The collective application of shorebird tracking data to conservation

Addressing urgent conservation issues, like the drastic declines of North American migratory birds, requires creative, evidence-based, efficient, and collaborative approaches. Over 50% of monitored North American shorebird populations have lost over 50% of their abundance since 1980. To address these declines, we developed a partnership of scientists and practitioners called the Shorebird Science and Conservation Collective (hereinafter "the Collective"). Here, we present this successful case study as an example for others engaged in translational science. The Collective acts as an intermediary whereby dedicated staff collate and analyze data contributions from scientists to support knowledge requests from conservation practitioners. Data contributions from 74 organizations include over 6.7 million shorebird locations forming movement paths of 3,345 individuals representing 36 species tracked across the Americas. We describe the founding and structure of the Collective and conservation activities we supported in our first two years. As the volume of scientific data on animal movements continues to grow, groups like the Collective can be vital liaisons to rapidly integrate and interpret research to support conservation action.

ecology↗

bioRxiv2023

RFIDeep: Unfolding the Potential of Deep Learning forRadio-Frequency Identification

O_LIAutomatic monitoring of wildlife is becoming a critical tool in the field of ecology. In particular, Radio-Frequency IDentification (RFID) is now a widespread technology to assess the phenology, breeding, and survival of many species. While RFID produces massive datasets, no established fast and accurate methods are yet available for this type of data processing. Deep learning approaches have been used to overcome similar problems in other scientific fields and hence might hold the potential to overcome these analytical challenges and unlock the full potential of RFID studies. C_LIO_LIWe present a deep learning workflow, coined "RFIDeep", to derive ecological features, such as breeding status and outcome, from RFID mark-recapture data. To demonstrate the performance of RFIDeep with complex datasets, we used a long-term automatic monitoring of a long-lived seabird that breeds in densely packed colonies, hence with many daily entries and exits. C_LIO_LITo determine individual breeding status and phenology and for each breeding season, we first developed a one-dimensional convolution neural network (1D-CNN) architecture. Second, to account for variance in breeding phenology and technical limitations of field data acquisition, we built a new data augmentation step mimicking a shift in breeding dates and missing RFID detections, a common issue with RFIDs. Third, to identify the segments of the breeding activity used during classification, we also included a visualisation tool, which allows users to understand what is usually considered a "black box" step of deep learning. With these three steps, we achieved a high accuracy for all breeding parameters: breeding status accuracy = 96.3%; phenological accuracy = 86.9%; breeding success accuracy = 97.3%. C_LIO_LIRFIDeep has unfolded the potential of artificial intelligence for tracking changes in animal populations, multiplying the benefit of automated mark-recapture monitoring of undisturbed wildlife populations. RFIDeep is an open source code to facilitate the use, adaptation, or enhancement of RFID data in a wide variety of species. In addition to a tremendous time saving for analyzing these large datasets, our study shows the capacities of CNN models to autonomously detect ecologically meaningful patterns in data through visualisation techniques, which are seldom used in ecology. C_LI

ecology↗

bioRxiv2022

Introducing Mouffet, a unified framework to make model creation easier and more reproducible

O_LIBiological and ecological models are being increasingly used to explain the natural world. Model creation is an iterative process requiring two steps: training and evaluating the models. However, this process can become complex when multiple models are trained and evaluated at the same time. Besides, development steps can be lost, reducing the reproducibility of model creation. C_LIO_LIWe introduce Mouffet, an open-source Python framework that aims to make model creation easier, more robust, and more reproducible. It provides a set of configuration files and high-level Python interfaces that help managing data, training, and evaluating models. To improve reproducibility, every step of the model creation process, including the options used, are saved. C_LIO_LIMouffet introduces the notion of scenarios that allow users to define multiple training or evaluation tasks in a single configuration file. This not only facilitates model creation but enables users to define experimental plans to study the effect of selected parameters on training or evaluation. C_LIO_LIWhile initially developed for deep learning models, Mouffet is independent of the implementation of the models. Therefore, it could be successfully used to compare different modelling approaches. Besides, its ease of use makes it a choice tool for ecologists, even when not familiar with complex model creation. C_LI

ecology↗

bioRxiv2022

Free meals during breeding: increased resource access does not benefit Arcic-nesting shorebirds

AO_SCPLOWBSTRACTC_SCPLOWArctic ecosystems are facing intensifying impacts of climate change, notably an increase in air temperature that can boost local productivity. Yet whether such resource surge can benefit declining migratory birds is unclear. Here we experimentally increased prey abundance and measure its effect on the body condition, nesting patterns, and nesting success of the white-rumped sandpiper (Calidris fuscicollis). We captured females at the beginning and at the end of their incubation to assess body condition and we installed small temperature probes inside their nests to measure their incubation recess. To estimate nest survival, we regularly monitored experimental and control nests during two consecutive summers (2016-2017). For both experimental years with contrasting nest success (73% vs. 21%), we found no evidence of an effect of our supplementation experiment mimicking an increased abundance of arthropods in the Canadian Arctic. This suggests that in situ resources are not limiting during incubation. Breeding strategies and success in shorebirds seem to be driven by inter-individual traits related to body condition upon the initiation of incubation.

ecology↗

bioRxiv2022

Long-term population decline of a genetically homogenous continental-wide top Arctic predator

Genetic analysis can provide valuable information for conservation programs by unraveling the demographic trajectory of populations, by estimating effective population size, or by inferring genetic differentiation between populations. Here, we investigated the genetic differentiation within the Snowy Owl (Bubo scandiacus), a species identified as vulnerable by the IUCN, to (i) quantify connectivity among wintering areas, (ii) to evaluate current genetic diversity and effective population size and (iii) to infer changes in the historical effective population size changes from the last millennia to the recent past. The Snowy Owl, a highly mobile top predator, breeds across the Arctic tundra which is a region especially sensitive to current climate change. Using SNP-based analyses on Snowy Owls sampled across the North American nonbreeding range, we found an absence of genetic differentiation among individuals located up to 4,650 km apart. Our results suggest high genetic intermixing and effective dispersal at the continental scale despite documented philopatry to nonbreeding sites in winter. Reconstructing the population demographic indicated that North American Snowy Owls have been steadily declining since the Last Glacial Maximum ca 20,000 years ago and concurrently with global increases in temperature. Conservation programs should now consider North American Snowy Owls as a single, genetically homogenous continental-wide population which is most likely sensitive to the long-term global warming occurring since the Last Glacial Maximum.

ecology↗

bioRxiv2022

When host populations move north, but disease moves south: counter-intuitive impacts of climate warming on disease spread

Empirical observations and mathematical models show that climate warming can lead to the northern (or, more generally, poleward) spread of host species ranges and their corresponding diseases. Here, we explore an unexpected possibility whereby climate warming induces disease spread in the opposite direction to the directional shift in the host species range. To test our hypothesis, we formulate a reaction-diffusion equation model with a Susceptible-Infected (SI) epidemiological structure for two host species, both susceptible to a disease, but spatially isolated due to distinct thermal niches, and where prior to climate warming the disease is endemic in the northern species only. Previous theoretical results show that species distributions can lag behind species thermal niches when climate warming occurs. As such, we find that climate warming, by shifting both species niches forward, may increase the overlap between northern and southern host species ranges, due to the northern species lagging behind its thermal tolerance limit, thus facilitating a southern disease spread. As our model is general, our findings may apply to viral, bacterial, and prion diseases that do not have thermal tolerance limits and are inextricably linked to their hosts distributions, such as the spread of rabies from arctic to red foxes.

ecology↗

bioRxiv2021

BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking CLU+ CAF expression with HSF1 signaling

Cancer-associated fibroblasts (CAFs) give rise to desmoplastic stroma, which supports tumor progression and metastasis, and comprises up to 90% of the tumor mass in pancreatic cancer. Recent work by us and others has shown that CAFs are transcriptionally rewired by adjacent cancer cells to form heterogeneous subtypes. Whether this rewiring is differentially affected by different driver mutations in cancer cells is largely unknown. Here we address this question by dissecting and comparing the stromal landscape of BRCA-mutated and BRCA Wild-type (WT) pancreatic ductal adenocarcinoma (PDAC). We comprehensively analyze PDAC samples from a cohort of 42 patients by laser-capture microdissection, RNA-sequencing and multiplexed immunofluorescence, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA-WT tumors. In particular, we detect an increase in a subset of Clusterin (CLU)-positive CAFs in BRCA-mutated tumors. We further unravel a network of stress responses upregulated in BRCA-mutated tumors. Using cancer organoids and cell co-cultures, we show that the transcriptional shift of pancreatic stellate cells into CLU+ CAFs is mediated through activation of heat-shock factor 1 (HSF1), the transcriptional regulator of Clu. Our findings unravel a new dimension of stromal heterogeneity, influenced by germline mutations in cancer cells, with direct translational implications for clinical research. SignificanceBRCA1/2 mutations initiate some of the deadliest cancers, yet the fibroblastic microenvironment of BRCA-mutated cancers remains uncharted. Our work addresses a major unsolved question - to what extent is the tumor microenvironment determined by cancer mutations? We find that BRCA mutations in the cancer cells affect the composition of CAFs in PDAC. These findings have direct implications for diagnosis and for efforts to exploit CAFs for therapy.

cancer biology↗

bioRxiv2021

New Records of California Serogroup Virus in Aedes Mosquitoes and First Detection in Simulioidae Flies from Northern Canada and Alaska

An expected consequence of climate warming is an expansion of the geographic distribution of biting insects and associated arthropod-borne diseases (arboviruses). Emerging and reemerging arboviruses that can affect human health are likely to pose significant consequences for Northern communities where access to health resources is limited. In the North American Arctic, little is known about arboviruses. Thus, in 2019, we sampled biting insects in Nunavik (Kuujjuaq), Nunavut (Igloolik, Karrak Lake and Cambridge Bay), Northwest Territories (Igloolik and Yellowknife) and Alaska (Fairbanks). The main objective was to detect the presence of California serogroup viruses (CSGv) - a widespread group of arboviruses across North America and that is known to cause a wide range of symptoms, ranging from mild febrile illness to fatal encephalitis. Biting insects were captured twice daily for a 7-day period in mid-summer, using a standardized protocol consisting of 100 figure-eight movements of a sweep net. Captured specimens were separated by genus (mosquitoes) or by superfamily (other insects), and then grouped into pools of 75 by geographical locations. In total, 5079 Aedes mosquitoes and 1014 Simulioidae flies were caught. We report the detection of CSGv RNA in mosquitoes captured in Nunavut (Karrak Lake) and Nunavik (Kuujjuaq). We also report, for the first time in North America, the presence of CSGv RNA in Simulioidae flies. These results highlight the potential of biting insects for tracking any future emergence of arboviruses in the North, thereby providing key information for public health in Northern communities.

microbiology↗

bioRxiv2021

Pancreatic cancer prognosis is predicted by a novel ATAC-array technology for assessing chromatin accessibility

We investigated tumor-cell-intrinsic chromatin accessibility patterns of pancreatic ductal adenocarcinoma (PDAC) by ATAC-seq on EpCAM+ PDAC malignant epithelial cells, sorted from 54 freshly resected human tumors, and discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identified two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further developed a novel chromatin accessibility microarray methodology termed "ATAC-Array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this novel methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validated ATAC-array technology in both the original ATAC-Seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a novel, lowcost, clinically feasible technology for assessing chromatin accessibility profiles.

cancer biology↗

bioRxiv2020

Spatiotemporal changes in biodiversity by ecosystem engineers: how beavers structure the richness of large mammals

High levels of biodiversity may be needed to maintain ecosystem functioning. By creating niches for other species, ecosystem engineers have the potential to promote biodiversity, but it is unclear how this translates across spatiotemporal scales. We evaluated the long-term impact of ecosystem engineering by beavers (Castor canadensis) on the diversity of mobile species. We tested the hypothesis that the spatial distribution of engineered habitats in different states resulting from ecosystem engineering by beavers increases the biodiversity of large mammals across spatial scales. We tested a second hypothesis that engineered habitat in different states resulting from ecosystem engineering by beavers drive the diversity of large mammals. We compared the richness and composition of boreal mammals using camera traps between habitats with and without history of occurrence by beavers within a protected area, where trapping, hunting, and forest exploitation are prohibited. We found that unique species were mostly found in specific engineered habitats, with ponds and wet meadows showing more species than dry meadows. In addition to the increased diversity of dispersal-limited species, our results show that beavers promote the diversity of mobile species at both local and landscape scales, signaling the importance of niche creation in structuring animal communities across scales.

ecology↗

bioRxiv2020

Derivation of predator functional responses using a mechanistic approach in a natural system

The functional response is central to our understanding of any predator-prey system as it establishes the link between trophic levels. Most functional responses are evaluated using phenomenological models linking predator acquisition rate and prey density. However, our ability to measure functional responses using such an approach is often limited in natural systems and the use of inaccurate functions can profoundly affect the outcomes of population and community models. Here, we develop a mechanistic model based on extensive data to assess the functional response of a generalist predator, the arctic fox (Vulpes lagopus), to various tundra prey species (lemmings and the nests of geese, passerines and sandpipers). We found that predator acquisition rates derived from the mechanistic model were consistent with field observations. Although sigmoidal functional responses were previously used to model fox-prey population dynamics, none of our simulations resulted in a saturating response in all prey species. Our results highlight the importance of predator searching components in predator-prey interactions, especially predator speed, while predator acquisition rates were not limited by handling processes. By combining theory with field observations, our study provides evidences that predator acquisition rate is not systematically limited at the highest prey densities observed in a natural system. We reinforce the idea that functional response categories, typically types I, II, and III, should be considered as particular cases along a continuum. Specific functions derived with a mechanistic approach for a range of densities observed in natural communities should improve our ability to model and understand predator-prey systems.

ecology↗