Search bioRxiv⌕ Search

Biology subjects

Bevacqua, D.

Publications and source records attributed to Bevacqua, D..

15 recordsLinked to original sources

Extra-lineage tissue programs define the transcription states of human pancreatic cancer

Cancers acquire alternate transcriptional states as they evolve, but the origins, timing and determinants of this plasticity are poorly understood in many tumours. We investigated the transcriptional states of pancreatic cancer by integrating [~]1000 tumour-enriched genomes and transcriptomes from 464 patients combined with scRNA-seq, multiome profiling, and spatial proteomics. Four epithelial states covering the spectrum of lineage plasticity were identified (Classical-1, Classical-2, Basal-1, Basal-2). Comparing these states to normal and pan-cancer human single cell atlases showed each state reflects distinct tissue programs found in other malignancies. Single cell analysis uncovered that the main transcription state of this disease (Classical-1) emerges before KRAS mutations. Spatial proteomics from patients and cancer-free donors showed that the Classical-1 program emerges during acinar-to-ductal metaplasia, and also unexpectedly, in normal ducts without disrupting their morphology. Overall, these findings link the extensive lineage plasticity potential of this organ to the origins of the transcriptional states.

cancer biology↗

Transcriptomic, Genomic, and Clinical Characterization of Morphological Classes in Localized and Metastatic Pancreatic Cancer

BackgroundHistomorphology is a strong prognostic biomarker correlated with basal-like and classical programs in surgically resected pancreatic ductal adenocarcinoma (PDAC). However, the spectrum of morphology and its biological associations remain poorly defined in advanced disease. ObjectivesWe explored the transcriptomic and genomic underpinnings and clinical relevance of morphological classes across localized and metastatic PDAC. DesignWe unified morphological classifications into four classes: glandular, cribriform, solid, and squamous. We integrated transcriptome and whole-genome sequencing following laser-capture microdissection with morphological classifications in 348 PDAC patients, where half of the cohort included locally advance and metastatic stages to uncover molecular associations. ResultsNon-glandular morphologies comprised three distinct classes that were enriched in metastatic disease. Transcriptomic profiling exhibited that glandular tumours predominantly expressed classical epithelial programs, although a subset displayed partial or full epithelial- mesenchymal transition signatures. In contrast, non-glandular morphologies showed basal-like transcriptional programs with subtype-specific pathways, including ciliogenesis in cribriform tumours, extracellular matrix remodelling and immune evasion in solid tumours, and keratinisation programs in squamous tumours. The solid class was significantly enriched in liver metastatic lesions and was associated with increased intra-tumoural morphological heterogeneity, whole-genome doubling, KRAS major allelic imbalance, and elevated KRAS-ERK signalling. ConclusionNon-glandular morphologies identify biologically distinct PDAC tumour states that are enriched in liver metastases and associated with subtype-specific transcriptional programs and KRAS-driven genomic alterations.

cancer biology↗

The subclonal footprint of pervasive early dissemination in pancreatic cancer

Early is too late describes a central problem in pancreatic cancer referring to its relentless drive to disseminate and highlights the need to understand how this disease spreads so rapidly. In this study, we profiled 1,013 samples from 277 donors, including tissue whole genome and RNA sequencing combined with plasma whole genome sequencing at [~]25x. Strikingly, local primary tumours, including some reaching 7cm, were found to shed little to no circulating tumour DNA (ctDNA). Instead, metastatic burden in the liver but not extrahepatic sites, was a main physiologic determinant of ctDNA levels. Whole-genome duplication (WGD), high cell cycle activity, and non-glandular differentiation emerged as tumour-intrinsic features related to increased ctDNA shedding. By contrast, decreased shedding was related to extrinsic features including a reactive microenvironment and unexpectedly, humoral immunity. Analysis of tumour clonal architecture showed that in patients with low ctDNA levels, the signal disproportionately originated from subclones and this signal persisted even when the primary tumour was removed. Disseminated subclones were a significant source of ctDNA in early-stage patients. Longitudinal analysis of patients revealed that subclones seeded metastases and shed ctDNA in the blood years before detection. This first report of paired tissue and plasma whole genomes in pancreatic cancer is a unique resource and has broad implications for disease surveillance, treatment monitoring, and early detection in this disease.

cancer biology↗

Shifting ecological niches of Prunus species under climate change

Climate change is strongly impacting agriculture, reducing crop production and shifting the geographic distribution of suitable areas for crop cultivation. To safeguard future global yield and feed a growing world population, the migration of crop production areas to new suitable sites represents a way to adapt to a changing climate. Here, we aim to identify the ecological niche of Prunus species, namely peach, plum, almond, apricot and sweet cherry, and examine their expected future shifts under climate change. For each Prunus species, we selected from the literature processed-based phenological models for dormancy break, blooming and fruit ripening, whose fulfillment determines whether an area is suitable for crop cultivation. Historically, the ecological niche of Prunus species spans mid-low European latitudes, while higher latitudes fail satisfying the forcing requirements for blooming and fruit ripening. In future, this constraint is expected to become less restrictive with a northwards expansion of the suitable areas. However, this will be contrasted by a contraction of the niche at low latitudes due to dormancy break failures. While bridging established mechanistic knowledge on the climatic effects of plant phenological traits with citizen science observations, our work brings new insights into how fruit crops will respond to global warming.

ecology↗

Optimizing fungicide deployment in a connected crop landscape while balancing epidemic control and environmental sustainability

Bioaggressors cause significant losses in crop production, and the efficacy of control methods, primarily based on chemical compounds, comes with considerable environmental and health costs. Plant protection practices implemented locally undermine the mobility of bioaggressors, which can spread between fields, connecting different crop populations. As a consequence, the yield in a given field depends also on the management of connected fields. In this study, we evaluate the efficiency of different fungicide deployment strategies across a national-scale agriculture landscape, balancing the conflicting objectives of maximizing crop production and reducing fungicide use. We use a climate-driven metapopulation model describing the dynamics of the peach (Prunus persica)-brown rot (caused by Monilinia spp.) pathosystem in continental France. Fungicide deployment strategies are based on indices or algorithms, considering network topology, epidemic risk, territory, and stochastic sampling, which prioritize sites to be treated first. Eventually, we focus solely on the objective of maximizing harvest revenue, assuming that untreated fruit can be marketed at higher prices. The optimal strategy depends on the treatment allocation threshold: if up 20% of the area is treated, epidemic risk provides the most effective prioritization. If more than 40% of the area can be treated, a combination of random sampling and risk-based prioritization proves optimal. When considering a single objective, we find that the higher the consumers willingness to pay for untreated fruit, the larger the proportion of untreated sites becomes. Fungicide use could be avoided if untreated fruit were sold at 2.9 times the price of treated fruit.

ecology↗

Phenological and epidemiological impacts of climate change on peach production

Agricultural food security is threatened by climate change impacts, which can distress crop growth and favor the spread of infectious diseases. Here, we examined the synergism of the two potentially most disruptive causes of future yield failure in peach production: the effects of global climate change on fruit growth and on the spread of fungal diseases. Coupling a phenological and epidemiological model across the French continental territory, we provided projections of yield losses for four peach cultivars (early, mid-early, mid-late, and late) in the XXI century under different climate change scenarios. Global warming is expected to impair fruit phenology with blooming failure events in the south-western part of the country. This will be less extreme under the more moderate emission scenario, even though sporadic blooming failures will still occur. In contrast, future warmer and drier conditions will decrease brown rot-induced yield loss in the historical locations devoted to peach cultivation. To adapt to these changes, the benefits of shifting peach production sites to new suitable areas are evaluated. Thanks to this strategy, the peach national yield could still be fulfilled even under the most extreme climate change scenario. Comprehensive mathematical frameworks, that concomitantly consider the climatic effects on the plant hosts and on their pathogens, are required to provide reliable future predictions of crop yields and to inform control and adaptation strategies to guarantee food security under global warming.

ecology↗

A metapopulation framework integrating landscape heterogeneity to model an airborne plant pathogen: the case of brown rot of peach in France

Plant disease dynamics are driven by the concurrent interplay of host susceptibility, pathogen presence, and environmental conditions. While host susceptibility and local environmental conditions can readily be characterised, the transmission of an airborne pathogen depends on the biotic and abiotic conditions of the surrounding environment. Here, we propose an original metapopulation framework integrating landscape heterogeneity, in terms of climate and host density, where local populations of plant hosts are connected via air-masses which allow pathogen dispersal. We explicitly account for climatic drivers affecting pathogen release and survival while modelling aerial dispersal using Lagrangian simulations, as well as host phenology and infection. We calibrate the model parameters according to the literature and using Approximate Bayesian Computation against observations of brown rot incidence in French peach orchards from 2001-2020 across an area of 50,000 km2. We used the model to produce maps of risk, distinguishing site dangerousness (risk of causing secondary infection in other sites) and vulnerability (risk of becoming infected) across the our study area. We find that most dangerous and vulnerable sites are located along the Rhone Valley, due to the concurrence of high density of peach cultivation, a suitable climate and persistent airborne connections. Our work represents a first step to integrate metapopulation theory, epidemiology and air-mass movements to inform plant protection strategies, and could be adapted to optimize crop protection under future climate projections.

ecology↗

Benefits and costs of a global cooperative surveillance strategy to control trans-boundary crop pathogens

Trans-boundary diseases are extremely complex to control and can cause global socioeconomic damages. In the context of crop protection, surveillance strategies are usually designed according to administrative boundaries. In this study, we investigate to which extent this geographical scale of surveillance is suitable for long-distance dispersed pathogens. We lever on a global epidemic network, presented in a previous work, describing worldwide potential transport of P. graminis, the causal agent of stem rust of wheat. We conceive two surveillance strategies: "Country-based" and "Cooperative" and we compare their performances, in terms of minimizing the number of sentinels deployed, to achieve given surveillance targets, both at the global and country level. As expected, we find that a "Cooperative" strategy is more efficient at the global scale, and this is particularly true for intermediate targets of surveillance. However, costs and benefits of adopting a "Cooperative" strategy are not equally distributed among countries. Medium size countries in central Europe and Asia are those that would benefit most from a cooperative strategy. On the other hand, Greece and Finland, having a small wheat production but placed in important Puccinia pathways, are those that should deploy, in the global interest, more sentinels than they would place in the national interest. Among the major wheat producers, China is the only country that would have a cost from a cooperative strategy, while India, Russia, United States, France and Ukraine would have the most benefits. It follows that the acknowledgement of these discrepancies could help to achieve general stakeholder support for a global international cooperative surveillance system.

plant biology↗

A climate-driven compartmental model for fungal diseases in fruit orchards: The impacts of climate change on a brown rot-peach system

As a well-known driving force of diseases in crops, climate change is likely to impact future crop yields. In the present work, we account for climate-related influences on the key parameters of a SIR-type epidemiological model for fungal diseases in stone fruit aimed at simulating different observed epidemic patterns, and, eventually, evaluating the possible impacts of climate change on the disease-induced yield loss. Brown rot disease in peach orchards is used here as a study system. We contrasted simulation results with epidemiological measures collected from an experimental orchard in Avignon (southern France) in two consecutive years, characterized by dissimilar brown rot outbreaks. The capacity of our climate-driven model to adequately reproduce the observed disease patterns suggests temperature and precipitation as key drivers of brown rot epidemics. Overall, the model predicts a potential decrease of brown rot severity under warmer and drier climatic conditions. To comprehensively understand the effect of future climate change on peach yield, alterations of crop phenology must also be accounted for. We thus build a model that considers the synergism between the two factors: vulnerability to the pathogen and varying phenology. Using plausible climate change scenarios, we find that the peach yield in the considered Mediterranean region will be considerably impaired: although brown rot-related yield losses are expected to decrease in warmer and drier climatic conditions, climate change will hinder fruit blooming and consequently the yield because milder winters will impede the achievement of dormancy. By deepening our understanding of climatic impacts on crop fungal infections, the present study may serve as a useful tool to plan and implement suitable adaptation strategies for peach cultivation.

plant biology↗

Maximize crop production and environmental sustainability: insights from an ecophysiological model of plant-pest interactions and multi-criteria decision analysis

Satisfying the demand for agricultural products while also protecting the environment from negative impacts of agriculture is a major challenge for crop management. We used an ecophysiological model of plant-pest interaction and multi-criteria decision analysis to optimize crop management when considering two contrasting objectives: (1) maximizing crop production and (2) minimizing environmental impact related to fertilization, irrigation and pesticide deployment. The model provides an indicator of crop production for 27 management scenarios, obtained combining three levels of fertilization, irrigation and pesticide use, respectively. We computed the environmental impact relevant to each management scenario by means of a weighted sum of costs assigned to fertilization, irrigation and pesticide use. We identified the optimal scenarios with respect to the considered objectives analysing the Pareto front. These scenarios were mostly characterized by high fertilization and no pesticide use. We evaluated the multi-functionality of the optimal scenarios by mean of the Gini coefficient: the scenario better assuring the equality between the two objectives was characterized by high fertilization, intermediate irrigation and no pesticide. Although our results remain qualitative and not immediately transferable to agronomic practices, our analytical framework provides a useful tool to evidence trade-offs among two contrasting objectives and provide solutions to act in an efficient way by leaving a certain degree of freedom to the political decision maker.

ecology↗

The role of interference between vectors in control of plant diseases

Aphids are the primary vector of plant viruses. Transient aphids, which probe several plants per day, are considered to be the principal vectors of non-persistently transmitted (NPT) viruses. However, resident aphids, which can complete their life cycle on a single host and are affected by agronomic practices, can transmit NPT viruses as well. Moreover, they can interfere both directly and indirectly with transient aphids, eventually shaping plant disease dynamics. By mean of an epidemiological model, originally accounting for ecological principles and agronomic practices, we explore the consequences of fertilization and irrigation, pesticide deployment and roguing of infected plants on the spread of viral diseases in crops. Our results indicate that the spread of NPT viruses can be i) both reduced or increased by fertilization and irrigation, depending on whether the interference is direct or indirect; ii) counter-intuitively increased by pesticide application and iii) reduced by roguing infected plants. We show that a better understanding of vectors interactions would enhance our understanding of disease transmission, supporting the development of disease management strategies. Author summaryA range of both experimental and theoretical studies show that the behaviour and population dynamics of insects depend strongly upon interactions with other insect species. These interactions have the potential to greatly affect the dynamics of insect-vectored plant disease, as transmission of viruses is intimately dependent on the local density of vectors, as well as how they select and move between potential host plants. Surprisingly, the effects of interaction between vector species on epidemics remains little studied and even worse understood, probably because experimentation is costly and difficult. Here, we present a model which permits to investigate the effect of interaction between a virus, two vector species, and the host plant on the spread of viral disease in crops. In this study, our model is used to explore the consequences of common agronomic practices on epidemics. Our study highlights the importance of exploring vectors interactions to enhance the understanding of disease transmission, supporting the development of disease management strategies.

ecology↗

Control strategies for heterogeneous plant pathogens: evolutionary and agricultural consequences

Disease control can induce both demographic and evolutionary responses in host-parasite systems. Foreseeing the outcome of control therefore requires knowledge of the eco-evolutionary feedback between control and system. Previous work has assumed that control strategies have a homogeneous effect on the parasite population. However, this is not true when control targets those traits that confer to the parasite heterogeneous levels of resistance, which can additionally be related to other key parasite traits, through evolutionary trade-offs. In this work, we develop a minimal model coupling epidemiological and evolutionary dynamics to explore possible trait-dependent effects of control strategies. Particularly, we consider a parasite expressing continuous levels of a trait determining resource exploitation, and a control treatment that can be either positively or negatively correlated with that trait. We demonstrate the potential of trait-dependent control by considering that the decision maker may want to minimise both the damage caused by the disease and the use of treatment, due to possible environmental or economic costs. We identify efficient strategies showing that the optimal type of treatment depends on the amount applied. Our results pave the way for the study of control strategies based on evolutionary constraints, such as collateral sensitivity and resistance costs, which are receiving increasing attention for both public health and agricultural purposes.

ecology↗

Surveillance of airborne plant disease dissemination at continental scale using air mass trajectory analysis and network theory

Sustainable management of plant disease outbreaks in agriculture is one of the main challenges of the next years to restore economic and environmental viability of farming practices. Improving early-detection capabilities and disease surveillance is increasingly seen as an obligate step to design appropriate and effective prophylactic measures. In this context, plant diseases caused by wind-dispersed pathogens represent an interesting case of study, since they are particularly complex and hard to observe directly, especially if compared to other dissemination means, and demand for a multidisciplinary approach to be dealt with. Wind dispersal could imply a geographic differentiation in pathogens spreading potential, due to the emerging of local meteorological features. In this work we analyze the spatio-temporal patterns of wind connectivity in Europe and the Mediterranean basin in order to identify possible pathways of Puccinia graminis spores, the causal agent of stem rust of wheat. By running backwards Lagrangian simulations merging a biological layer coupled with a pathogen viability model, we investigate possible long-distance connections between regions in the study area across different seasons. We characterized these regions in terms of network centrality indicators to identify possible spreaders of stem rust of wheat, founding that Central and Western European regions appears to provide highest connectivity for the spread of P. graminis.

plant biology↗

Shifts in the thermal niche of fruit trees under climate change: the case of peach cultivation inFrance.

Climate influences plant phenological traits, thus playing a key role in defining the geographical range of crops. Foreseeing the impact of climate change on fruit trees is essential to inform policy decisions to guide the adaptation to new climatic conditions. To this end, we propose and use a phenological process-based model to assess the impacts of climate change upon the phenology, the suitability and the distribution of economically important cultivars of peach (Prunus persica), across the entire continental France. The model combines temperature dependent sub-models of dormancy, blooming, fruit survival and ripening, using chilling units, forcing units, frost occurrence and growing degree days, respectively. We find that climate change will have divergent impacts upon peach production. On the one hand, blooming will occur earlier, warmer temperatures will decrease spring frost occurrence and fruit ripening will be easily achieved before the start of fall. On the other hand, milder winters will impede the plant buds from breaking endodormancy, with consequent abnormal patterns of fruit development or even blooming failure. This latter impact will dramatically shift the geographic range of sites where peach production will be profitable. This shift will mainly be from the south of France (Languedoc-Roussillon, Rhone-Alpes and Provence-Alpes-Cote dAzur), to northwestern areas where the winter chilling requirement will still be fulfilled. Our study provides novel insights for understanding and forecasting climate change impacts on peach phenology and it is the first framework that maps the ecological thermal niche of peach at national level.

plant biology↗

An eco-physiological model coupling plant growth and aphid population dynamics

Empirical studies have shown that particular irrigation/fertilization regimes can control pest populations in agroecosystems. This appears to promise that the ecological concept of bottom-up control can be applied to pest management. However, a conceptual framework is necessary to develop a mechanistic basis for empirical evidence. Here we couple a mechanistic plant growth model with a pest population model. We demonstrate its utility by applying it to the peach - green aphid system. Aphids are herbivores which feed on the plant phloem, deplete plants resources and (potentially) transmit viral diseases. The model reproduces system properties observed in field studies and shows under which conditions the diametrically-opposed plant vigour and plant stress hypotheses find support. We show that the effect of fertilization/irrigation on the pest population cannot be simply reduced as positive or negative. In fact, the magnitude and direction of any effect depends on the precise level of fertilization/irrigation and on the date of observation. We show that a new synthesis of experimental data can emerge by embedding a mechanistic plant growth model, widely studied in agronomy, in a consumer-resource modelling framework, widely studied in ecology. The future challenge is to use this insight to inform practical decision making by farmers and growers.

plant biology↗