Biology subjects

Munoz-Tamayo, R.

Publications and source records attributed to Munoz-Tamayo, R..

10 recordsLinked to original sources

bioRxiv2024

Dynamic sensitivity analysis of a mathematical model describing the effect of the macroalgae Asparagopsis taxiformis on rumen fermentation and methane production under in vitro continuous conditions

Ruminants play an important role in global warming by emitting enteric methane (CH4) through the degradation of feeds by the rumen microbiota. To better understand the dynamics fermentation outputs, including CH4 and volatile fatty acids (VFA) production, mathematical models have been developed. Sensitivity analysis (SA) methods quantify the contribution of model input parameters (IP) to the variation of an output variable of interest. In animal science, SA are usually conducted in static condition. In this work, we hypothesized that including the dynamic aspect of the rumen fermentation to SA can be useful to inform on optimal experimental conditions aimed at quantifying the key mechanisms driving CH4 and VFA production. Accordingly, the objective of this work was to conduct a dynamic SA of a rumen fermentation model under in vitro continuous conditions (close to the real in vivo conditions). Our model case study integrates the effect of the macroalgae Asparagopsis taxiformis (AT) on the fermentation. AT has been identified as a potent CH4 inhibitor via the presence of bromoform, an anti-methanogenic compound. We computed Shapley effects over time for quantifying the contribution of 16 IPs to CH4 (mol/h) and VFA (mol/l) variation. Shapley effects integrate the three contribution types of an IP to output variable variation (individual, via the interactions and via the dependence/correlation). We studied three diet scenarios accounting for several doses of AT relative to Dry Matter (DM): control (0% DM of AT), low treatment (LT: 0.25% DM of AT) and high treatment (HT: 0.50% DM of AT). Shapley effects revealed that hydrogen (H2) utilizers microbial group via its Monod H2 affinity constant highly contributed (> 50%) to CH4 variation with a constant dynamic over time for control and LT. A shift on the impact of microbial pathways driving CH4 variation was revealed for HT. IPs associated with the kinetic of bromoform utilization and with the factor modeling the direct effect of bromoform on methanogenesis were identified as influential on CH4 variation in the middle of fermentation. Whereas, VFA variation for the three diet scenarios was mainly explained by the kinetic of fibers degradation, showing a high constant contribution (> 30%) over time. The simulations computed for the SA were also used to analyze prediction uncertainty. It was related to the dynamic of dry matter intake (DMI, g/h), increasing during the high intake activity periods and decreasing when the intake activity was low. Moreover, CH4 (mol/h) simulations showed a larger variability than VFA simulations, suggesting that the reduction of the uncertainty of IPs describing the activity of the H2 utilizers microbial group is a promising lead to reduce the overall model uncertainty. Our results highlighted the dynamic nature of the influence of metabolic pathways on CH4 productions under an anti-methanogenic treatment. SA tools can be further exploited to design optimal experiments studying rumen fermentation and CH4 mitigation strategies. These optimal experiments would be useful to build robust models that can guide the development of sustainable nutrition strategies.

systems biology↗

bioRxiv2023

Integrating microbial abundance time series with fermentation dynamics of the rumen microbiome via mathematical modelling

The rumen represents a dynamic microbial ecosystem where fermentation metabolites and microbial concentrations change over time in response to dietary changes. The integration of microbial genomic knowledge and dynamic modelling can enhance our system-level understanding of rumen ecosystems function. However, such an integration between dynamic models and rumen microbiota data is lacking. The objective of this work was to integrate rumen microbiota time series determined by 16S rRNA gene amplicon sequencing into a dynamic modelling framework to link microbial data to the dynamics of the volatile fatty acids (VFA) production during fermentation. For that, we used the theory of state observers to develop a model that estimates the dynamics of VFA from the data of microbial functional proxies associated with the specific production of each VFA. We determined the microbial proxies using CowPi to infer the functional potential of the rumen microbiota and extrapolate their functional modules from KEGG (Kyoto Encyclopedia of Genes and Genomes). The approach was challenged using data from an in vitro RUSITEC experiment and from an in vivo experiment with four cows. The model performance was evaluated by the coefficient of variation of the root mean square error (CRMSE). For the in vitro case study, the mean CVRMSE were 9.8% for acetate, 14% for butyrate and 14.5% for propionate. For the in vivo case study, the mean CVRMSE were 16.4% for acetate, 15.8% for butyrate and 19.8% for propionate. The mean CVRMSE for the VFA molar fractions were 3.1% for acetate, 3.8% for butyrate and 8.9% for propionate. Ours results show the promising application of state observers integrated with microbiota time series data for predicting rumen microbial metabolism.

systems biology↗

bioRxiv2022

Dynamic genome-based metabolic modeling of the predominant cellulolytic rumen bacterium Fibrobacter succinogenes S85

Fibrobacter succinogenes is a cellulolytic predominant bacterium that plays an essential role in the degradation of plant fibers in the rumen ecosystem. It converts cellulose polymers into intracellular glycogen and the fermentation metabolites succinate, acetate, and formate. We developed dynamic models of F. succinogenes S85 metabolism on glucose, cellobiose, and cellulose on the basis of a network reconstruction done with the Automatic Reconstruction of metabolic models (AuReMe) workspace. The reconstruction was based on genome annotation, 5 templates-based orthology methods, gap-filling and manual curation. The metabolic network of F. succinogenes S85 comprises 1565 reactions with 77% linked to 1317 genes, 1586 unique metabolites and 931 pathways. The network was reduced using the NetRed algorithm and analyzed for computation of Elementary Flux Modes (EFMs). A yield analysis was further performed to select a minimal set of macroscopic reactions for each substrate. The accuracy of the models was acceptable in simulating F. succinogenes carbohydrate metabolism with an average coefficient of variation of the Root mean squared error of 19%. Resulting models are useful resources for investigating the metabolic capabilities of F. succinogenes S85, including the dynamics of metabolite production. Such an approach is a key step towards the integration of omics microbial information into predictive models of the rumen metabolism.

systems biology↗

bioRxiv2022

Disentangling the dynamics of energy allocation to provide a proxy of robustness in fattening pigs

BackgroundThere is a growing need to improve robustness characteristics in fattening pigs, but this trait is difficult to phenotype. Our first objective was to develop a robustness proxy on the basis of modelling of longitudinal energetic allocation coefficient to growth for fattening pigs. Consequently, the environmental variance of this allocation coefficient was considered as a proxy of robustness. The second objective was to estimate its genetic parameters and correlation with traits under selection as well with phenotypes routinely collected on farms. A total of 5848 pigs, from Pietrain NN paternal line, were tested at the AXIOM boar testing station (Azay-sur-Indre, France) from 2015 to 2022. This farm was equipped with automatic feeding system, recording individual weight and feed intake at each visit. We used a dynamic linear regression model to characterize the evolution of the allocation coefficient between cumulative net energy available, estimated from feed intake, and cumulative weight gain during fattening period. Longitudinal energetic allocation coefficients were analysed using a two-step approach, to estimate both its genetic variance and the genetic variance in the residual variance, trait LSR. ResultsThe LSR trait, that could be interpreted as an indicator of the response of the animal to perturbations/stress, showed low heritability (0.05{+/-}0.01). The trait LSR had high favourable genetic correlations with average daily growth (-0.71{+/-}0.06) and unfavourable with feed conversion ratio (-0.76{+/-}0.06) and residual feed intake (-0.83{+/-}0.06). The analysis of the relationship between estimated breeding values (EBV) LSR quartiles and phenotypes routinely collected on farms shows the most favourable situation for animals from quartile with the weakest EBV LSR, i.e., the most robust. ConclusionsThese results show that selection for robustness based on deviation from energetic allocation coefficient to growth can be considered in breeding programs for fattening pigs.

genetics↗

bioRxiv2020

Modelling the impact of the macroalgae Asparagopsis taxiformis on rumen microbial fermentation

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSThe red macroalgae Asparagopsis taxiformis is a potent natural supplement for reducing methane production from cattle. A. taxiformis contains several anti-methanogenic compounds including bromoform that inhibits directly methanogenesis. The positive and adverse effects of A. taxiformis on the rumen microbiota are dose-dependent and operate in a dynamic fashion. It is therefore key to characterize the dynamic response of the rumen microbial fermentation for identifying optimal conditions on the use of A. taxiformis as a dietary supplement for methane mitigation. Accordingly, the objective of this work was to model the effect of A. taxiformis supplementation on the rumen microbial fermentation under in vitro conditions. We adapted a published mathematical model of rumen microbial fermentation to account for A. taxiformis supplementation. We modelled the impact of A. taxiformis on the fermentation and methane production by two mechanisms, namely (i) direct inhibition of the growth rate of methanogens by bromoform and (ii) hydrogen control on sugars utilization and on the flux allocation towards volatile fatty acids production. We calibrated our model using a multi-experiment estimation approach that integrated experimental data with six macroalgae supplementation levels from a published in vitro study assessing the dose-response impact of A. taxiformis on rumen fermentation. Resultsour model captured satisfactorily the effect of A. taxiformis on the dynamic profile of rumen microbial fermentation for the six supplementation levels of A. taxiformis with an average determination coefficient of 0.88 and an average coefficient of variation of the root mean squared error of 15.2% for acetate, butyrate, propionate, ammonia and methane. Conclusionsour results indicated the potential of our model as prediction tool for assessing the impact of additives such as seaweeds on the rumen microbial fermentation and methane production in vitro. Additional dynamic data on hydrogen and bromoform are required to validate our model structure and look for model structure improvements. We expect this model development can be useful to help the design of sustainable nutritional strategies promoting healthy rumen function and low environmental footprint.

microbiology↗

bioRxiv2020

Quantifying growth perturbations over the fattening period in swine via mathematical modelling

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSResilience can be defined as the capacity of animals to cope with short-term perturbations in their environment and return rapidly to their pre-challenge status. In a perspective of precision livestock farming, it is key to create informative indicators for general resilience and therefore incorporate this concept in breeding goals. In the modern swine breeding industry, new technologies such as automatic feeding system are increasingly common and can be used to capture useful data to monitor animal phenotypes such as feed efficiency. This automatic and longitudinal data collection integrated with mathematical modelling has a great potential to determine accurate resilience indicators, for example by measuring the deviation from expected production levels over a period of time. ResultsThis work aimed at developing a modelling approach for facilitating the quantification of pig resilience during the fattening period, from approximately 34 kg to 105 kg of body weight. A total of 13 093 pigs, belonging to three different genetic lines were monitored (Pietrain, Pietrain NN and Duroc) since 2015, and body weight measures registered (approximately 11.1 million of weightings) with automatic feeding systems. We used the Gompertz model and linear interpolation on body weight data to quantify individual deviations from expected production, thereby creating a resilience index (ABC). The estimated heritabilities of ABC are low but not zero from 0.03 to 0.04 ({+/-} 0.01) depending on the breed. ConclusionsOur model-based approach can be useful to quantify pig responses to perturbations using exclusively the growth curves and should contribute to the genetic improvement of resilience of fattening pigs by providing a resilience index.

systems biology↗

bioRxiv2018

On Parameter Interpretability of Phenomenological-Based Semiphysical Models

Empirical and phenomenological based models are used to represent biological and physiological processes. Phenomenological models are derived from the knowledge of the mechanisms that underlie the behaviour of the system under study, while empirical models are derived from analysis of data to quantify relationships between variables of interest. For studying biological systems, the phenomenological modeling approach offers the great advantage of having a structure with variables and parameters with physical meaning that enhance the interpretability of the model and its further used for decision making. The interpretability property of models, however, remains a vague concept. In this study, we tackled the interpretability property for parameters of phenomenological-based models. To our knowledge, this property has not been deeply discussed, perhaps by the implicit assumption that interpretability is inherent to the phenomenological-based models. We propose a conceptual framework to address the parameter interpretability and its implications for parameter identifiability. We use as battle horse a simple but relevant model representing the enzymatic degradation of {beta}-casein by a Lactococcus lactis bacterium.

bioengineering↗

bioRxiv2018

Hydrogenotrophic methanogens of the mammalian gut: functionally similar, thermodynamically different. A modelling approach

Methanogenic archaea occupy a functionally important niche in the gut microbial ecosystem of mammals. Our purpose was to quantitatively characterize the dynamics of methanogenesis by integrating microbiology, thermodynamics and mathematical modelling. For that, in vitro growth experiments were performed with pure cultures of key methanogens from the human and ruminant gut, namely Methanobrevibacter smithii, Methanobrevibacter ruminantium and Methanobacterium formicium. Microcalorimetric experiments were performed to quantify the methanogenesis heat flux. We constructed an energetic-based mathematical model of methanogenesis. Our model captured efficiently the dynamics of methanogenesis with concordance correlation coefficients of 0.94 for CO2, 0.99 for H2 and 0.97 for CH4. Together, experimental data and model enabled us to quantify metabolism kinetics and energetic patterns that were specific and distinct for each species despite their use of analogous methane-producing pathways. Then, we tested in silico the interactions between these methanogens under an in vivo simulation scenario using a theoretical modelling exercise. In silico simulations suggest that the classical competitive exclusion principle is inapplicable to gut ecosystems and that kinetic information alone cannot explain gut ecological aspects such as microbial coexistence. We suggest that ecological models of gut ecosystems require the integration of microbial kinetics with nonlinear behaviours related to spatial and temporal variations taking place in mammalian guts. Our work provides novel information on the thermodynamics and dynamics of methanogens. This understanding will be useful to construct new gut models with enhanced prediction capabilities and could have practical applications for promoting gut health in mammals and mitigating ruminant methane emissions.

microbiology↗

bioRxiv2018

Towards the quantitative characterization of piglets’ robustness to weaning: A modelling approach

Weaning is a critical transition phase in swine production in which piglets must cope with different stressors that may affect their health. During this period, the prophylactic use of antibiotics is still frequent to limit piglet morbidity, which raises both economic and public health concerns such as the appearance of antimicrobial-resistant microbes. With the interest of developing tools for assisting health and management decisions around weaning, it is key to provide robustness indexes that inform on the animals capacity to endure the challenges associated to weaning. This work aimed at developing a modelling approach for facilitating the quantification of piglet resilience to weaning. We monitored 325 Large White pigs weaned at 28 days of age and further housed and fed conventionally during the post-weaning period without antibiotic administration. Body weight and diarrhoea scores were recorded before and after weaning, and blood was sampled at weaning and one week later for collecting haematological data. We constructed a dynamic model based on the Gompertz-Makeham law to describe live weight trajectories during the first 75 days after weaning following the rationale that the animal response is partitioned in two time windows (a perturbation and a recovery window). Model calibration was performed for each animal. Our results show that the transition time between the two time windows, as well as the weight trajectories are characteristic for each individual. The model captured the weight dynamics of animals at different degrees of perturbation, with an average coefficient of determination of 0.99, and a concordance correlation coefficient of 0.99. The utility of the model is that it provides biological parameters that inform on the amplitude and length of perturbation, and the rate of animal recovery. Our rationale is that the dynamics of weight inform on the capability of the animal to cope with the weaning disturbance. Indeed, there were significant correlations between model parameters and individual diarrhoea scores and haematological traits. Overall, the parameters of our model can be useful for constructing weaning robustness indexes by using exclusively the growth curves. We foresee that this modelling approach will provide a step forward in the quantitative characterization of robustness.\n\nImplicationsThe quantitative characterization of animal robustness at weaning is a key step for management strategies to improve health and welfare. This characterization is also instrumental for the further design of selection strategies for productivity and robustness. Within a precision livestock farming optic, this study develops a mathematical modelling approach to describe the body weight of piglets from weaning with the rationale that weight trajectories provide central information to quantify the capability of the animal to cope with the weaning disturbance.

systems biology↗

bioRxiv2018

A parsimonious software sensor for estimating the individual dynamic pattern of methane emissions from cattle

Large efforts have been deployed in developing methods to estimate methane emissions from cattle. For large scale applications, accurate and inexpensive methane predictors are required. Within a livestock precision farming context, the objective of this work was to integrate real-time data on animal feeding behaviour with an in silico model for predicting the individual dynamic pattern of methane emission in cattle. The integration of real-time data with a mathematical model to predict variables that are not directly measured constitutes a software sensor. We developed a dynamic parsimonious grey-box model that uses as predictor variables either dry matter intake (DMI) or the intake time (IT). The model is described by ordinary differential equations. Model building was supported by experimental data of methane emissions from respiration chambers. The data set comes from a study with finishing beef steers (cross-bred Charolais and purebred Luing finishing). DMI and IT were recorded with load cells. A total of 37 individual dynamic patterns of methane production were analysed. Model performance was assessed by concordance analysis between the predicted methane output and the methane measured in respiration chambers. The model predictors DMI and IT performed similarly with a Lins concordance correlation coefficient (CCC) of 0.78 on average. When predicting the daily methane production, the CCC was 0.99 for both DMI and IT predictors. Consequently, on the basis of concordance analysis, our model performs very well compared with reported literature results for methane proxies and predictive models. Since IT measurements are easier to obtain than DMI measurements, this study suggests that a software sensor that integrates our in silico model with a real-time sensor providing accurate IT measurements is a viable solution for predicting methane output in a large scale context.\n\nImplicationsReducing methane emissions from ruminants is a major target for sustainable and efficient livestock farming. For the animal, methane production represents a loss of feed energy. For the environment, methane exerts a potent greenhouse effect. Methane mitigation strategies require accurate, non-invasive and inexpensive techniques for estimating individual methane emissions on farm. In this study, we integrate measurements of feeding behaviour in cattle and a mathematical model to estimate individual methane production. Together, model and measurements form a software sensor that efficiently predicts methane output. Our software sensor is a promising approach for estimating methane emissions at large scale.

bioengineering↗