Prats Soler, Clara
Total activity: 58
Professional category
Tenure-track 1 lecturers
Doctoral courses
Física aplicada y simulación en ciencias
University degree
LLICENCIAT FÍSICA
Research group
SC-SIMBIO - Complex systems. Computer simulation of materials and biological systems
Department
Department of Physics and Nuclear Engineering
School
Barcelona School of Agricultural Engineering (ESAB)
E-mail
clara.pratsupc.edu
Contact details
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Orcid
0000-0002-1398-7559 Open in new window
ResearcherID
L-4797-2014 Open in new window
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1 to 50 of 58 results
  • The microbial individual-based model INDISIM-YEAST ready to be used in the free access NetLogo modelling environment

     Portell Canal, Xavier; Gras Moreu, Anna Maria; Prats Soler, Clara; Ginovart Gisbert, Marta
    Date of publication: 2014
    Book chapter

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  • Evolution and role of corded cell aggregation in Mycobacterium tuberculosis cultures

     Cáceres, Neus; Vilaplana, Cristina; Prats Soler, Clara; Marzo, Elena; Llopis Fuste, Isaac; Valls Ribas, Joaquim; Lopez Codina, Daniel; Cardona, Pere-Joan
    Tuberculosis
    Vol. 93, num. 6, p. 690-698
    DOI: 10.1016/j.tube.2013.08.003
    Date of publication: 2013-11
    Journal article

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    The aim of this study was to evaluate the evolution and role of corded cell aggregation in Mycobacterium tuberculosis cultures according to growth time and conditions. Thus, in standard culture using aerated 7H9 Middlebrook broth supplemented with 0.05% Tween 80, a dramatic CFU decrease was observed at the end of the exponential phase. This phase was followed by a stable stationary phase that led to dissociation between the optical density (O.D.) and CFU values, together with the formation of opaque colonies in solid culture. Further analysis revealed that this was due to cording. Scanning electron microscopy showed that cording led to the formation of very stable coiled structures and corded cell aggregations which proved impossible to disrupt by any of the physical means tested. Modulation of cording with a high but non-toxic concentration of Tween 80 led to a slower growth rate, avoidance of a sudden drop-off to the stationary phase, the formation of weaker cording structures and the absence of opaque colonies, together with a lower survival at later time-points. An innovative automated image analysis technique has been devised to characterize the cording process. This analysis has led to important practical consequences for the elaboration of M. tuberculosis inocula and suggests the importance of biofilm formation in survival of the bacilli in the extracellular milieu.

  • Mighty small: Observing and modeling individual microbes becomes big science

     Kreft, Jan-Ulrich; Plugge, Caroline M.; Grimm, Volker; Prats Soler, Clara; Leveau, Johan H. J.; Banitz, Thomas; Baines, Stephen; Clark, James; Ros, Alexandra; Klapper, Isaac; Topping, Chris J.; Field, Anthony J.; Schuler, Andrew; Litchman, Elena; Hellweger, Ferdi L.
    Proceedings of the National Academy of Sciences of the United States of America
    Vol. 110, num. 45, p. 18027-18028
    DOI: 10.1073/pnas.1317472110
    Date of publication: 2013-11-05
    Journal article

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  • Spatial growth of Mycobacterium tuberculosis in lungs: the bubble model

     Prats Soler, Clara; Valls Ribas, Joaquim; Vilaplana, Cristina; Marzo, Elena; Cardona, Pere-Joan; Lopez Codina, Daniel
    International Conference on Environmental, Industrial and Applied Microbiology
    p. 513-
    Presentation's date: 2013-10-03
    Presentation of work at congresses

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  • The microbial individual-based model INDISIM-YEAST ready to be used in the free access NetLogo modelling environment

     Portell Canal, Xavier; Gras Moreu, Anna Maria; Prats Soler, Clara; Ginovart Gisbert, Marta
    International Conference on Environmental, Industrial and Applied Microbiology
    p. 734
    Presentation's date: 2013
    Presentation of work at congresses

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    Low dose aerosol fitness at the innate phase of murine infection better predicts virulence amongst clinical strains of mycobacterium tuberculosis  Open access

     Cáceres, Neus; Llopis Fuste, Isaac; Marzo, Elena; Prats Soler, Clara; Vilaplana, Cristina; García de Viedma, Darío; Samper, Sofia; Lopez Codina, Daniel; Cardona, Pere-Joan
    PLoS one
    Vol. 7, num. 1, p. e29010-
    DOI: 10.1371/journal.pone.0029010
    Date of publication: 2012-01-03
    Journal article

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    Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings: The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 104 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 102 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. Conclusions/Significance: The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism of the induction of active TB derived from the dynamic hypothesis of latent tuberculosis infection.

  • Agent-based Models in malaria elimination strategy design

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Valls Ribas, Joaquim
    European Meeting on Cybernetics and Systems Research
    Presentation's date: 2012-04
    Presentation of work at congresses

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  • Granuloma formation in lungs due to M.tuberculosis infection through an Individual-based Model

     Llopis Fuste, Isaac; Prats Soler, Clara
    MYCOSPAIN
    Presentation's date: 2012-07-10
    Presentation of work at congresses

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  • A biphasic model for fitting optical density measurements to bacterial cell counts and its application on the instantaneous growth rate evaluation

     Ye, Wei Hong; Prats Soler, Clara; Bover-Cid, Sara; Garriga, Margarita; Lopez Codina, Daniel
    International ICFMH Symposium (Food Micro)
    p. 612
    Presentation's date: 2012-09-04
    Presentation of work at congresses

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  • A two-compartment system allows lymphatic tissues to control M. tuberculosis infection in the peripheral organs

     Vilaplana Massaguer, Cristina; Prats Soler, Clara; Marzo, Elena; Barril, Carles; Llopis Fuste, Isaac; Díaz, Julio; Valls Ribas, Joaquim; Lopez Codina, Daniel; Cardona, Pere-Joan
    European Congress of Immunology
    Presentation's date: 2012-09-07
    Presentation of work at congresses

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  • A Bacterial Individual-based Virtual Bioreactor to Test Handling Protocols in a NetLogo Platform

     Ginovart Gisbert, Marta; Prats Soler, Clara
    Vienna International Conference on Mathematical Modelling
    p. 647-652
    DOI: 10.3182/20120215-3-AT-3016.00115
    Presentation's date: 2012
    Presentation of work at congresses

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  • Modelización basada en el individuo (IBM) perspectiva multidisclipinar en microbiologia aplicada: alimentos, medioambiente y salud

     Prats Soler, Clara; Valls Ribas, Joaquim; Carbo Moliner, Rosa; Ginovart Gisbert, Marta; Giro Roca, Antoni; Gras Moreu, Anna Maria; Portell Canal, Xavier; Ferrer Savall, Jordi; Silbert, Moises; Lopez Codina, Daniel
    Competitive project

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  • Sensitivity analysis and individual-based models in the study of yeast populations

     Ginovart Gisbert, Marta; Prats Soler, Clara; Portell Canal, Xavier
    European Conference on Modelling and Simulation
    p. 41-47
    Presentation's date: 2011-06
    Presentation of work at congresses

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    Individual-based models (IBMs), the biological agent-based models, are currently being applied to the study of microbial systems. A microbial IBM of yeast populations growing in liquid bath cultures has already been designed and implemented in the simulator called INDISIM-YEAST. In order to improve its predictive capabilities and further its development, a deeper understanding of how the variation of the output of the model can be apportioned, qualitatively or quantitatively, to different sources of variation must be investigated. The aim of this study is to show how insights into the individual cell parameters of INDISIM-YEAST can be obtained combining local and global methods using classic and well-proven methods, and to illustrate how these simple methods provide useful, reliable results with this IBM. This work deals mainly with the use of screening methods, as the main task to perform here is that of identifying the most influential factors for this microbial IBM. This screening exercise has allowed the establishment of significant input factors to this IBM on yeast population growth, and the highlighting of those that require greater attention in the parameterization and calibration processes.

  • Analysis of the effect of inoculum characteristics on the first stages of a growing yeast population in beer fermentations by means of an individual-based model

     Ginovart Gisbert, Marta; Prats Soler, Clara; Portell Canal, Xavier; Silbert, Moises
    Journal of industrial microbiology and biotechnology
    Vol. 38, p. 153-165
    DOI: 10.1007/s10295-010-0840-4
    Date of publication: 2011
    Journal article

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  • Exploring the lag phase and growth initiation of a yeast culture by means of an individual-based model

     Ginovart Gisbert, Marta; Prats Soler, Clara; Portell Canal, Xavier; Silbert, Moises
    Food microbiology
    Vol. 28, num. 4, p. 810-817
    DOI: 10.1016/j.fm.2010.05.004
    Date of publication: 2011
    Journal article

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    The performance of fermentation processes is greatly influenced by the size and quality of inocula. The characterization of the replicative age is decided by the number of birth scars each yeast exhibits on its cellular membrane. Yeast ageing and inoculum size are factors that affect industrial fermentation, particularly those processes in which the yeast cells are reused such as the production of beer. This process reuses yeast cropped at the end of one fermentation in the following one, in a process called “serial repitching”. The aim of this study was to explore the effects of inoculum size and ageing on the first stages of the dynamics of yeast population growth. However, only Individual-based Models (IbMs) allow the study of small, well-characterized, microbial inocula. We used INDISIM-YEAST, based on the generic IbM simulator INDISIM, to carry out these studies. Several simulations were performed to analyze the effect of the inoculum size and genealogical age of the cells that made it up on the lag phase, first division time and specific growth rate. The shortest lag phase and time to the first division were obtained with largest inocula and with the youngest inoculated parent cells. Keywords: Individual-based model; Lag phase; Growth initiation; Yeast inoculum; Inoculum size; Yeast cell age.

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    Thermodynamic concepts in the study of microbial populations: age structure in plasmodium falciparum infected red blood cells  Open access

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Vidal-Mas, Jaume; Gargallo-Viola, Domingo; Guglietta, Antonio; Giro Roca, Antoni
    PLoS one
    Vol. 6, num. 10, p. e26690 1-e26690 11
    DOI: 10.1371/journal.pone.0026690
    Date of publication: 2011-10-31
    Journal article

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    Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretations. The infection process of Plasmodium falciparum parasitizing human red blood cells under laboratory cultivation conditions is used to illustrate the potential of Individual-based models in the context of predictive microbiology and parasitology. Experimental data from several in vitro cultures are compared to the outcome of an individual-based model and analysed from a thermodynamic perspective. This approach allows distinguishing between intrinsic and external constraints that give rise to the diversity in the infection forms, and it provides a criterion to quantitatively define transient and stationary regimes in the culture. Increasing the ability of models to discriminate between different states of microbial populations enhances their predictive capability which finally leads to a better the control over culture systems. The strategy here presented is of general application and it can substantially improve modelling of other types of microbial communities.

  • Microbial individual-based models and sensitivity analyses: local and global methods

     Ginovart Gisbert, Marta; Prats Soler, Clara; Portell Canal, Xavier
    International Conference on Predicitive Modeling in Foods
    p. 313-316
    Presentation's date: 2011-09-13
    Presentation of work at congresses

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    A microbial Individual-based Model (IbM) to deal with yeast populations growing in liquid batch cultures has been designed and implemented in a simulator called INDISIM-YEAST. Interesting qualitative results have already been achieved with its use in the study of fermentation profiles, small inocula dynamics and lag phase, among others. Nevertheless, in order to improve its predictive capabilities and further development, a deeper comprehension of how the variation of the output of the model can be apportioned to different sources of variation must be investigated. One way to consider a sensitivity analysis for this IbM, providing an understanding of how the model response variables react to changes in the inputs, is the statistical study of well-designed computer experiments. The aim of this contribution is to show how the insights into nine individual cell parameters of INDISIMYEAST, mainly related to uptake and reproduction sub-models, can be obtained by combining local and global sensitivity analyses using simple and classic methods. From data obtained with an extensive set of computer experiments, a study of the variability observed in the evolution of two outputs of this model, ethanol production and mean biomass of the population, was performed. In addition, mono-factorial (one-at-a-time) analyses and ANOVA-based global analyses were also carried out on these two outputs. The model is clearly less sensitive to some parameters than others, depending on the output controlled. Moreover, this study allows identification of the parameters which have the greatest impact on the corresponding outputs and their significant first-order interactions. This work must be understood as an exercise to set up the procedure to be used in a sensitivity analysis study involving microbial IbMs. The knowledge gained will facilitate future parameterization and calibration of different parameters and outputs depending on the purpose of any study.

  • New insights on the virulence determination of M. tuberculosis clinical strains by applying different "in vitro" and "in vivo" strategies

     Cáceres, Neus; Llopis Fuste, Isaac; Marzo, Elena; Vilaplana, Cristina; Díaz, Jorge; Alonso, María; García de Viedma, Darío; Alonso, Henar; Samper, Sofia; Prats Soler, Clara; Lopez Codina, Daniel; Cardona, Joan Pere
    International Conference on the Pathogenesis of Mycobacterial Infections
    p. 97
    Presentation's date: 2011-07-01
    Presentation of work at congresses

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  • Método de valoración de virulencia de cepas de Mycobacterium tuberculosis complex y uso de los agregados bacilares de cepas de Mycobacterium tuberculosis complex en cultivo líquido para dicha valoración

     Prats Soler, Clara; Llopis Fuste, Isaac; Lopez Codina, Daniel; Caceres Casademunt, Neus; Cardona Iglesias, Pere Joan; Vilaplana Massaguer, Cristina
    Date of request: 2011-06-22
    Invention patent

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    Método de valoración de virulencia de cepas de Mycobacterium tuberculosis complex y uso de los agregados bacilares de cepas de Mycobacterium tuberculosis complex en cultivo líquido para dicha valoración.

    Tras constatar que la mayor capacidad virulenta de cepas de Mycobacterium tuberculosis se relacionaba con el tamaño de las agrupaciones bacilares contenidas en el cultivo bacilar, el método propone valorar dicha virulencia a partir de la determinación de la distribución de tamaños de los agregados bacilares de cada cepa analizada a partir de muestras obtenidas tras su crecimiento en un medio líquido hasta la fase tardía del crecimiento logarítmico.

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    Population-based and individual-based modelling of high hydrostatic pressure effect in Listeria monocytogenes on sliced dry-cured ham  Open access

     Prats Soler, Clara; Bover Cid, Sara; Garriga, Margarita; Aymerich Calvet, Teresa; Ferrer Savall, Jordi; Lopez Codina, Daniel
    International ICFMH Symposium (Food Micro)
    p. 174
    Presentation's date: 2010-09-01
    Presentation of work at congresses

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    Combined use of local and global sensitivity analyses for the investigation of an individual-based model of yeast populations  Open access

     Prats Soler, Clara; Portell Canal, Xavier; Gras Moreu, Anna Maria; Ginovart Gisbert, Marta
    International ICFMH Symposium (Food Micro)
    p. 173
    Presentation's date: 2010-09-01
    Presentation of work at congresses

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  • Individual-based modelling and simulation of microbial processes: yeast fermentation and multi-species composting

     Prats Soler, Clara; Ferrer Savall, Jordi; Gras Moreu, Anna Maria; Ginovart Gisbert, Marta
    Mathematical and Computer Modelling of Dynamical Systems (online)
    Vol. 16, num. 3, p. 489-510
    DOI: 10.1080/13873954.2010.481809
    Date of publication: 2010-12-06
    Journal article

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    On the evolution of cell size distribution during bacterial growth cycle: experimental observations and individual-based model simulations  Open access

     Prats Soler, Clara; Ferrer Savall, Jordi; Lopez Codina, Daniel; Giro Roca, Antoni; Vives-Rego, Josep
    African journal of microbiology research
    Vol. 4, num. 5, p. 400-407
    Date of publication: 2010-03
    Journal article

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  • Contribution of individual-based models in malaria elimination strategy design

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Valls Ribas, Joaquim; Gargallo Viola, Domingo
    Parasite to prevention, advandes in understanding malaria
    p. 27
    DOI: 10.1186/1475-2875-9-S2-P9
    Presentation's date: 2010-10-20
    Presentation of work at congresses

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    Analysis of the population structure of Plasmodium falciparum-infected erythrocytes  Open access

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Gargallo Viola, Domingo; Valls Ribas, Joaquim
    Current opinion in celular host-pathogen interactions
    p. 3
    Presentation's date: 2010-09-05
    Presentation of work at congresses

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  • Optimization methods for individual-based model parameter estimation in predictive microbiology

     Prats Soler, Clara; Bernaerts, K.; Standaert, A.; Ferrer Savall, Jordi; Lopez Codina, Daniel; Van Impe, J.
    Vienna Conference on Mathematical Modelling
    p. 2635-2638
    Presentation's date: 2009
    Presentation of work at congresses

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    In the framework of microbiology, Individual-based Models are discrete models in which the main entities are microbes. Their use in simulations as ‘virtual experiments’ to predict the evolution of populations under specific conditions requires accurate setting of the parameters involved. We adapted and tested two optimization methods for Individual-based Model parameter estimation: the Nelder-Mead Threshold Accepting (NMTA) and the NEWUOA. These methods presented no convergence problems, and the best results in terms of time expenditure were derived with the latter.

  • Individual-based modelling and simulation of microbial processes: yeast fermentation and multispecies composting

     Prats Soler, Clara; Ferrer Savall, Jordi; Gras Moreu, Anna Maria; Ginovart Gisbert, Marta
    Vienna International Conference on Mathematical Modelling (MATHMOD 2009)
    Presentation's date: 2009-02-12
    Presentation of work at congresses

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    Individual-based modelling and simulation: towards a better understanding of growth dynamics from small inocula  Open access

     Dalmau Andreu, Roger; Portell Canal, Xavier; Prats Soler, Clara; Ginovart Gisbert, Marta; Giro Roca, Antoni
    SAFE Consortium International Congress on Food Safety: Novel Technologies and Food Quality, Safety and Health
    p. 153-154
    Presentation's date: 2009
    Presentation of work at congresses

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  • Mathematical modelling methodologies in predictive food microbiology: a SWOT analysis

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Vives-Rego, Josep
    International journal of food microbiology
    Vol. 134, num. 1-2, p. 2-8
    Date of publication: 2009-08
    Journal article

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    Effect of the inoculum characteristics on the first stages of a growing yeast population in beer fermentations by means of an individual-based Model  Open access

     Portell Canal, Xavier; Prats Soler, Clara; Silbert, Moises; Ginovart Gisbert, Marta
    International Conference on Environmental, Industrial and Applied Microbiology
    p. 292
    Presentation of work at congresses

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    Exploring lag phase and growth initiation of a yeast culture by means of an Individual-based Model  Open access

     Portell Canal, Xavier; Prats Soler, Clara; Silbert, Moises; Ginovart Gisbert, Marta
    International Conference on Predicitive Modeling in Foods
    p. 49-52
    Presentation of work at congresses

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  • Individual-based Modelling and simulation of microbial processes: yeast fermentation and multi-species composting

     Prats Soler, Clara; Ferrer Savall, Jordi; Gras Moreu, Anna Maria; Ginovart Gisbert, Marta
    Vienna Conference on Mathematical Modelling
    p. 1495-1506
    Presentation's date: 2009
    Presentation of work at congresses

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  • Microbiología predictiva: una herramienta imprescindible en seguridad alimentaria  Open access

     Prats Soler, Clara; Ferrer Savall, Jordi; Lopez Codina, Daniel
    Reunión Científica Hispano-Marroquí sobre Seguridad Alimentaria
    p. 34-35
    Presentation's date: 2009-10-20
    Presentation of work at congresses

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  • Mathematical modelling methodologies in predictive food microbiology: a SWOT analysis

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel; Vives-Rego, J
    International ICFMH Symposium
    p. 78
    Presentation's date: 2008
    Presentation of work at congresses

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  • INDISIM, an Individual-based Model to simulate microbial cultures

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel
    Annual conference of agent-based modelers, platform developers and users
    p. 1
    Presentation of work at congresses

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  • Individual-based modelling and flow cytometry: two suitable tools for predictive microbiology

     Prats Soler, Clara; Ferrer Savall, Jordi; Lopez Codina, Daniel; Vives-Rego, J
    International Conference on Simulation and Modelling in the Food and Bio-Industry
    p. 91-95
    Presentation's date: 2008
    Presentation of work at congresses

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  • Individual-based modelling of bacterial cultures in the study of the lag phase  Open access

     Prats Soler, Clara
    Department of Applied Physics, Universitat Politècnica de Catalunya
    Theses

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    La microbiologia predictiva és una de les parts més importants de la microbiologia dels aliments. En el creixement d'un cultiu bacterià es poden observar quatre fases: latència, exponencial, estacionària i mort. La fase de latència té un interès específic en microbiologia predictiva; al llarg de dècades ha estat abordada des de dues perspectives diferents: a nivell cel·lular i intracel·lular (escala microscòpica), i a nivell de població (escala macroscòpica). La primera estudia els processos que tenen lloc a l'interior dels bacteris durant la seva adaptació a les noves condicions del medi, com els canvis en l'expressió gènica i en el metabolisme. La segona descriu l'evolució de la població bacteriana per mitjà de models matemàtics continus i d'experiments que avaluen variables relacionades amb la densitat cel·lular. L'objectiu d'aquest treball és millorar la comprensió de la fase de latència dels cultius bacterians i dels fenòmens intrínsecs a la mateixa. Aquest objectiu s'ha abordat amb la metodologia Individual-based Modelling (IbM) amb el simulador INDISIM (INDividual DIScrete SIMulation), que ha calgut optimitzar. La IbM introdueix una perspectiva mecanicista a través de la modelització de les cèl·lules com a unitats bàsiques. Les simulacions IbM permeten estudiar el creixement d'entre 1 i 106 bacteris, així com els fenòmens que emergeixen de la interacció entre ells. Aquests fenòmens pertanyen al que anomenem escala mesoscòpica. Aquesta perspectiva és imprescindible per entendre l'efecte en la població dels processos d'adaptació individuals. Per tant, la metodologia IbM és un pont entre els individus i la població o, el que és el mateix, entre els models a escala microscòpica i a escala macroscòpica.En primer lloc hem estudiat dos dels diversos mecanismes que poden causar la fase de latència: inòculs amb massa mitjana petita, i canvis de medi.S'ha verificat també la relació de la durada de la latència amb variables com la temperatura o la grandària de l'inòcul. En aquest treball s'ha identificat la distribució de biomassa del cultiu com una variable cabdal per analitzar l'evolució del cultiu durant el cicle de creixement. S'han definit les funcions matemàtiques que anomenem distàncies per avaluar quantitativament l'evolució d'aquesta distribució.Hem abordat, també, la fase de latència des d'un punt de vista teòric. L'evolució de la velocitat de creixement al llarg del cicle ha permès distingir dues etapes en la fase de latència que anomenem inicial i de transició. L'etapa de transició s'ha descrit per mitjà d'un model matemàtic continu validat amb simulacions INDISIM. S'ha constatat que la fase de latència ha de ser vista com un procés dinàmic, i no com un simple període de temps descrit per un paràmetre. Les funcions distància també s'han utilitzat per avaluar les propietats del creixement balancejat.Alguns dels resultats de les simulacions amb INDISIM s'han corroborat experimentalment per mitjà de citometria de flux. S'ha comprovat, al llarg de les diverses fases del creixement, el comportament de la distribució de biomassa previst per simulació, així com l'evolució de les funcions distància. La coincidència entre els resultats experimentals i els de simulació no és trivial, ja que el sistema estudiat és molt complex. Per tant, aquests resultats permeten comprovar la bondat de la metodologia INDISIM.Finalment, hem avançat en l'optimització d'eines per parametritzar IbMs, un pas essencial per poder utilitzar les simulacions INDISIM de manera quantitativa. S'han adaptat i assajat els mètodes grid search, NMTA i NEWUOA. Aquest darrer mètode ha donat els millors resultats en termes de temps, mantenint una bona precisió en els valors òptims dels paràmetres. Per concloure, podem afirmar que INDISIM ha estat validat com una bona eina per abordar l'estudi dels estats transitoris com la fase de latència.

    Predictive food microbiology has become an important specific field in microbiology. Bacterial growth of a batch culture may show up to four phases: lag, exponential, stationary and death. The bacterial lag phase, which is of specific interest in the framework of predictive food microbiology, has generally been tackled with two generic approaches: at a cellular and intracellular level, which we call the microscopic scale, and at a population level, which we call the macroscopic scale. Studies at the microscopic level tackle the processes that take place inside the bacterium during its adaptation to the new conditions such as the changes in genetic expression and in metabolism. Studies at the macroscopic scale deal with the description of a population growth cycle by means of mathematical continuous modelling and experimental measurements of the variables related to cell density evolution.In this work we aimed to improve the understanding of the lag phase in bacterial cultures and the intrinsic phenomena behind it. This has been carried out from the perspective of Individual-based Modelling (IbM) with the simulator INDISIM (INDividual DIScrete SIMulation), which has been specifically improved for this purpose. IbM introduces a mechanistic approach by modelling the cell as an individual unit. IbM simulations deal with 1 to 106 cells, and allow specific study of the phenomena that emerge from the interaction among cells. These phenomena belong to the mesoscopic level.Mesoscopic approaches are essential if we are to understand the effects of cellular adaptations at an individual level in the evolution of a population.Thus, they are a bridge between individuals and population, or, to put it another way, between models at a microscopic scale and models at a macroscopic scale.First, we studied separately two of the several mechanisms that may cause a lag phase: the lag caused by the initial low mean mass of the inoculum, and the lag caused by a change in the nutrient source. The relationship among lag duration and several variables such as temperature and inoculum size were also checked. This analysis allowed identification of the biomass distribution as a very important variable to follow the evolution of the culture during the growth cycle. A mathematical tool was defined in order to assess its evolution during the different phases of growth: the distance functions.A theoretical approach to the culture lag phase through the dynamics of the growth rate allowed us to split this phase into two stages: initial and transition. A continuous mathematical model was built in order to shape the transition stage, and it was checked with INDISIM simulations. It was seen that the lag phase must be defined as a dynamic process rather than as a simple period of time. The distance functions were also used to discuss the balanced growth conditions.Some of the reported INDISIM simulation results were subjected to experimental corroboration by means of flow cytometry, which allow the assessment of size distributions of a culture through time. The dynamics of biomass distribution given by INDISIM simulations were checked, as well as the distance function evolution during the different phases of growth. The coincidence between simulations and experiments is not trivial: the system under study is complex; therefore, the coincidence in the dynamics of the different modelled parameters is a validation of both the model and the simulation methodology.Finally, we have made progress in IbM parameter estimation methods, which is essential to improve quantitative processing of INDISIM simulations.Classic grid search, NMTA and NEWUOA methods were adapted and tested, the latter providing better results with regard to time spent, which maintains satisfactory precision in the parameter estimation results.Above all, the validity of INDISIM as a useful tool to tackle transient processes such as the bacterial lag phase has been amply demonstrated.

  • Analysis and IbM simulation of the stages in bacterial lag phase: basis for an updated definition

     Prats Soler, Clara; Giro Roca, Antoni; Ferrer Savall, Jordi; Lopez Codina, Daniel; Vives-Rego, J
    Journal of theoretical biology
    Vol. 252, num. 1, p. 56-68
    DOI: doi:10.1016/j.jtbi.2008.01.019
    Date of publication: 2008-05
    Journal article

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    The lag phase is the initial phase of a culture that precedes exponential growth and occurs when the conditions of the culture medium differ from the pre-inoculation conditions. It is usually defined by means of cell density because the number of individuals remains approximately constant or slowly increases, and it is quantified with the lag parameter l. The lag phase has been studied through mathematical modelling and by means of specific experiments. In recent years, Individual-based Modelling (IbM) has provided helpful insights into lag phase studies. In this paper, the definition of lag phase is thoroughly examined. Evolution of the total biomass and the total number of bacteria during lag phase is tackled separately. The lag phase lasts until the culture reaches a maximum growth rate both in biomass and cell density. Once in the exponential phase, both rates are constant over time and equal to each other. Both evolutions are split into an initial phase and a transition phase, according to their growth rates. A population-level mathematical model is presented to describe the transitional phase in cell density. INDividual DIScrete SIMulation (INDISIM) is used to check the outcomes of this analysis. Simulations allow the separate study of the evolution of cell density and total biomass in a batch culture, they provide a depiction of different observed cases in lag evolution at the individual-cell level, and are used to test the population-level model. The results show that the geometrical lag parameter l is not appropriate as a universal definition for the lag phase. Moreover, the lag phase cannot be characterized by a single parameter. For the studied cases, the lag phases of both the total biomass and the population are required to fully characterize the evolution of bacterial cultures. The results presented prove once more that the lag phase is a complex process that requires a more complete definition. This will be possible only after the phenomena governing the population dynamics at an individual level of description, and occurring during the lag and exponential growth phases, are well understood.

  • Individual-based modelling: an essential tool for microbiology

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel
    Journal of biological physics
    Vol. 34, num. 1-2, p. 19-37
    Date of publication: 2008-04
    Journal article

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    Micro-organisms play a central role in every ecosystem and in the global biomass cycle. They are strongly involved in many fields of human interest, from medicine to the food industry and waste control. Nevertheless, most micro-organisms remain almost unknown, and nearly 99% of them have not yet been successfully cultured in vitro. Therefore, new approaches and new tools must be eveloped in order to understand the collective behaviour of microbial communities in any natural or artificial setting. In particular, theoretical and practical methodologies to deal with such systems at a mesoscopic level of description (covering the range from 100 to 108 cells) are required. Individualbased modelling (IBM) has become a widely used tool for describing complex systems made up of autonomous entities, such as ecosystems and social networks. Individual-based models (IBMs) provide some advantages over the traditional whole-population models: (a) they are bottom-up approaches, so they describe the behaviour of a system as a whole by establishing procedural rules for the individuals and for their interactions, and thus allow more realistic assumptions for the model of the individuals than population models do; (b) they permit the introduction of randomness and individual variability, so they can reproduce the diversity found in real systems; and (c) they can account for individual adaptive behaviour to their environmental conditions, so the evolution of the whole system arises from the dynamics that govern individuals in their pursuit of optimal fitness. However, they also present some drawbacks: they lack the clarity of continuous models and may easily become rambling, which makes them difficult to analyse and communicate. All in all, IBMs supply a holistic description of microbial systems and their emerging properties. They are specifically appropriate to deal with microbial communities in non-steady states, and spatially explicit IBMs are particularly appropriate to study laboratory and natural microbiological systems with spatial heterogeneity. In this paper, we review IBM methodology applied to microbiology. We also present some results obtained from the application of Individual Discrete Simulations, an IBM of ours, to the study of bacterial communities, yeast cultures and Plasmodium falciparum-infected erythrocytes in vitro cultures of Plasmodium falciparum-infected erythrocytes

  • Access to the full text
    Effect of the haematocrit layer geometry on Plasmodium falciparum static thin-layer in vitro cultures  Open access

     Ferrer Savall, Jordi; Rosal, M; Vidal, J; Prats Soler, Clara; Valls Ribas, Joaquim; Herreros, E; Lopez Codina, Daniel; Gargallo, D
    Malaria journal
    Vol. 7, num. 203
    DOI: doi:10.1186/1475-2875-7-203
    Date of publication: 2008-10
    Journal article

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    Several experimental trials exploring different settings have been carried out, covering haematocrit layer depths that ranged from 6 mm to 3 mm and separation between the walls of the culturing device that ranged from 7.5 mm to 9 mm. The obtained results have been analysed and compared to different system-level models and to an Individual-Based Model.

  • Evolution of biomass distribution during bacterial lag phase through flow cytometry, particle analysis and Individual-based Modelling

     Prats Soler, Clara; Ferrer Savall, Jordi; Flix, B; Giro Roca, Antoni; Lopez Codina, Daniel; Vives-Rego, J
    International Conference Predictive Modelling in Foods
    p. 301-304
    Presentation of work at congresses

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  • IbM: An essential tool for microbiology

     Ferrer Savall, Jordi; Prats Soler, Clara; Lopez Codina, Daniel
    International Conference of Biological Physics
    p. 91
    Presentation of work at congresses

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  • Individual based Modelling (IbM) de sistemas microbiológicos para el desarrollo sostenible: medio ambiente, seguridad alimentaria y salud

     Giro Roca, Antoni; Prats Soler, Clara; Lopez Codina, Daniel; Silbert, Moises; Valls Ribas, Joaquim; Gras Moreu, Anna Maria; Ginovart Gisbert, Marta; Portell Canal, Xavier; Ferrer Savall, Jordi
    Competitive project

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  • Individual-based model and simulation of Plasmodium falciparum infected erythrocyte in vitro cultures

     Ferrer Savall, Jordi; Vidal, J; Prats Soler, Clara; Valls Ribas, Joaquim; Herreros, E; Lopez Codina, Daniel; Giro Roca, Antoni; Gargallo, D
    Journal of theoretical biology
    Vol. 248, num. 3, p. 448-459
    Date of publication: 2007-10
    Journal article

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    Malaria is still one of the most fatal diseases in the world. Development of an effective treatment or vaccine requires the cultivation of the parasite that causes it: Plasmodium falciparum. Several methods for in vitro cultivation of P. falciparum infected erythrocytes have been successfully developed and described in the last 30 years. Some problems arising from the current harvests are the low parasitaemia and daily human supervision requirements. The lack of a suitable model for global culture behavior makes the assay of new methodologies a costly and tenuous task. In this paper we present a model and simulation tool for these systems. We use the INDividual DIScrete SIMulation protocol (INDISIM) to qualitatively reproduce the temporal evolution of the erythrocyte and merozoite populations. Whole system dynamics are inferred by setting the rules of behavior for each individual red blood cell, such as the nutrient uptake, metabolism and infection processes, as well as the properties and rules for the culture medium: composition, diffusion and external manipulation. We set the individual description parameters according to the values in published data, and allow population heterogeneity. Cells are arranged in a three-dimensional grid and the study is focused on the geometric constraints and physical design of experimental sets. Several published experimental cultures have been reproduced with computer simulations of this model, showing that the observed experimental behavior can be explained by means of individual interactions and statistical laws.

  • A physical interpretation of the microbial growth rate temperature dependence

     Prats Soler, Clara; Ferrer Savall, Jordi; Giro Roca, Antoni; Lopez Codina, Daniel; Valls Ribas, Joaquim
    Sitges Conference on Statistical Mechanics
    p. 161-163
    Presentation of work at congresses

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  • A mathematical analysis of the stages in bacterial lag phase

     Prats Soler, Clara; Giro Roca, Antoni; Lopez Codina, Daniel; Ferrer Savall, Jordi; Valls Ribas, Joaquim; Vives-Rego, Josep
    International ICFMH Symposium
    p. 550
    Presentation's date: 2006
    Presentation of work at congresses

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  • A mathematical analysis of the stages in bacterial lag phase

     Prats Soler, Clara; Giro Roca, Antoni; Lopez Codina, Daniel; Ferrer Savall, Jordi; Valls Ribas, Joaquim; Vives-Rego, Josep
    International ICFMH Symposium
    Presentation's date: 2006-08-30
    Presentation of work at congresses

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  • Spatial properties in Individual- based modelling of microbial systems. Study of the composting process.

     Prats Soler, Clara; Ferrer Savall, Jordi; Giro Roca, Antoni; Lopez Codina, Daniel; Valls Ribas, Joaquim
    Date of publication: 2006-10
    Book chapter

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  • Individual-based modelling of bacterial cultures to study the microscopic causes of the lag phase

     Prats Soler, Clara; Lopez Codina, Daniel; Giro Roca, Antoni; Ferrer Savall, Jordi; Valls Ribas, Joaquim
    Journal of theoretical biology
    Vol. 241, num. 4, p. 939-953
    Date of publication: 2006-08
    Journal article

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    The lag phase has been widely studied for years in an effort to contribute to the improvement of food safety. Many analytical models have been built and tested by several authors. The use of Individual-based Modelling (IbM) allows us to probe deeper into the behaviour of individual cells; it is a bridge between theories and experiments when needed. INDividual DIScrete SIMulation (INDISIM) has been developed and coded by our group as an IbM simulator and used to study bacterial growth, including the microscopic causes of the lag phase. First of all, the evolution of cellular masses, specifically the mean mass and biomass distribution, is shown to be a determining factor in the beginning of the exponential phase. Secondly, whenever there is a need for an enzyme synthesis, its rate has a direct effect on the lag duration. The variability of the lag phase with different factors is also studied. The known decrease of the lag phase with an increase in the temperature is also observed in the simulations. An initial study of the relationship between individual and collective lag phases is presented, as a complement to the studies already published. One important result is the variability of the individual lag times and generation times. It has also been found that the mean of the individual lags is greater than the population lag. This is the first in a series of studies of the lag phase that we are carrying out. Therefore, the present work addresses a generic system by making a simple set of assumptions.

  • Spatial properties in individual based simulations of microbiological systems, study of the composting process

     Prats Soler, Clara; Ferrer Savall, Jordi; Giro Roca, Antoni; Lopez Codina, Daniel; Valls Ribas, Joaquim
    International Conference on Environmental, Industrial and Applied Microbiology
    p. 461-465
    Presentation of work at congresses

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