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Traulsen A.,Max Planck Institute for Evolutionary Biology | Pacheco J.M.,University of Minho | Pacheco J.M.,ATP group | Luzzatto L.,Instituto Toscano Tumori | Dingli D.,Mayo Medical School
BioEssays | Year: 2010

Clonal disease is often regarded as almost synonymous with cancer. However, it is becoming increasingly clear that our bodies harbor numerous mutant clones that are not tumors, and mostly give rise to no disease at all. Here we discuss three somatic mutations arising within the hematopoietic system: BCR-ABL, characteristic of chronic myeloid leukemia; mutations of the PIG-A gene, characteristic of paroxysmal nocturnal hemoglobinuria; the V617F mutation in the JAK2 gene, characteristic of myeloproliferative diseases. The population frequencies of these three blood disorders fit well with a hierarchical model of hematopoiesis. The fate of any mutant clone will depend on the target cell and on the fitness advantage, if any, that the mutation confers on the cell. In general, we can expect that only a mutation in a hematopoietic stem cell will give long-term disease; the same mutation taking place in a cell located more downstream may produce just a ripple in the hematopoietic ocean. Copyright © 2010 WILEY Periodicals, Inc.

van Segbroeck S.,Vrije Universiteit Brussel | van Segbroeck S.,Free University of Colombia | Santos F.C.,New University of Lisbon | Santos F.C.,ATP Group | And 2 more authors.
PLoS Computational Biology | Year: 2010

Human societies are organized in complex webs that are constantly reshaped by a social dynamic which is influenced by the information individuals have about others. Similarly, epidemic spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to avoid contact with those infected and to remain in touch with the healthy. Here we study disease dynamics in finite populations in which infection occurs along the links of a dynamical contact network whose reshaping may be biased based on each individual's health status. We adopt some of the most widely used epidemiological models, investigating the impact of the reshaping of the contact network on the disease dynamics. We derive analytical results in the limit where network reshaping occurs much faster than disease spreading and demonstrate numerically that this limit extends to a much wider range of time scales than one might anticipate. Specifically, we show that from a population-level description, disease propagation in a quickly adapting network can be formulated equivalently as disease spreading on a well-mixed population but with a rescaled infectiousness. We find that for all models studied here - SI, SIS and SIR - the effective infectiousness of a disease depends on the population size, the number of infected in the population, and the capacity of healthy individuals to sever contacts with the infected. Importantly, we indicate how the use of available information hinders disease progression, either by reducing the average time required to eradicate a disease (in case recovery is possible), or by increasing the average time needed for a disease to spread to the entire population (in case recovery or immunity is impossible). © 2010 Van Segbroeck et al.

Santos F.C.,New University of Lisbon | Santos F.C.,ATP group | Pacheco J.M.,ATP group | Pacheco J.M.,University of Minho | Skyrms B.,University of California at Irvine
Journal of Theoretical Biology | Year: 2011

A finite-population dynamic evolutionary model is presented, which shows that increasing the individual capacity of sending pre-play signals (without any pre-defined meaning), opens a route for cooperation. The population dynamics leads individuals to discriminate between different signals and react accordingly to the signals received. The proportion of time that the population spends in different states can be calculated analytically. We show that increasing the number of different signals benefits cooperative strategies, illustrating how cooperators may take profit from a diverse signaling portfolio to forecast future behaviors and avoid being cheated by defectors. © 2011 Elsevier Ltd.

Santos F.C.,New University of Lisbon | Santos F.C.,ATP Group | Pinheiro F.L.,ATP Group | Lenaerts T.,Free University of Colombia | And 3 more authors.
Journal of Theoretical Biology | Year: 2012

Understanding the evolutionary mechanisms that promote and maintain cooperative behavior is recognized as a major theoretical problem where the intricacy increases with the complexity of the participating individuals. This is epitomized by the diverse nature of Human interactions, contexts, preferences and social structures. Here we discuss how social diversity, in several of its flavors, catalyzes cooperative behavior. From the diversity in the number of interactions an individual is involved to differences in the choice of role models and contributions, diversity is shown to significantly increase the chances of cooperation. Individual diversity leads to an overall population dynamics in which the underlying dilemma of cooperation is changed, benefiting the society as whole. In addition, we show how diversity in social contexts can arise from the individual capacity for organizing their social ties. As such, Human diversity, on a grand scale, may be instrumental in shaping us as the most sophisticated cooperative entities on this planet. © 2011 Elsevier Ltd.

Dingli D.,Rochester College | Pacheco J.M.,University of Minho | Pacheco J.M.,ATP Group
BMC Biology | Year: 2011

Stem cells are the target of mutations that can lead to life threatening diseases. However, stem cell populations tend to be small and therefore clonal expansion of mutant cells is highly sensitive to stochastic fluctuations. The evolutionary dynamics of mutations in these cells is discussed, taking into consideration the impact of such mutations on the reproductive fitness of cells. We show how stochastic effects can explain clinical observations, including extinction of acquired clonal stem cell disorders. © 2011 Dingli and Pacheco; licensee BioMed Central Ltd.

Van Segbroeck S.,Free University of Colombia | Van Segbroeck S.,Vrije Universiteit Brussel | Santos F.C.,New University of Lisbon | Santos F.C.,ATP Group | And 4 more authors.
New Journal of Physics | Year: 2011

We have studied the evolution of cooperation in structured populations whose topology coevolves with the game strategies of the individuals. Strategy evolution proceeds according to an update rule with a free parameter, which measures the selection pressure. We explore how this parameter affects the interplay between network dynamics and strategy dynamics. A dynamical network topology can influence the strategy dynamics in two ways: (i) by modifying the expected payoff associated with each strategy and (ii) by reshaping the imitation network that underlies the evolutionary process. We show here that the selection pressure tunes the relative contribution of each of these two forces to the final outcome of strategy evolution. The dynamics of the imitation network plays only a minor role under strong selection, but becomes the dominant force under weak selection. We demonstrate how these findings constitute a mechanism supporting cooperative behavior. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.

Werner B.,Max Planck Institute for Evolutionary Biology | Dingli D.,Rochester College | Lenaerts T.,Free University of Colombia | Lenaerts T.,Vrije Universiteit Brussel | And 3 more authors.
PLoS Computational Biology | Year: 2011

Most tissues in multicellular organisms are maintained by continuous cell renewal processes. However, high turnover of many cells implies a large number of error-prone cell divisions. Hierarchical organized tissue structures with stem cell driven cell differentiation provide one way to prevent the accumulation of mutations, because only few stem cells are long lived. We investigate the deterministic dynamics of cells in such a hierarchical multi compartment model, where each compartment represents a certain stage of cell differentiation. The dynamics of the interacting system is described by ordinary differential equations coupled across compartments. We present analytical solutions for these equations, calculate the corresponding extinction times and compare our results to individual based stochastic simulations. Our general compartment structure can be applied to different tissues, as for example hematopoiesis, the epidermis, or colonic crypts. The solutions provide a description of the average time development of stem cell and non stem cell driven mutants and can be used to illustrate general and specific features of the dynamics of mutant cells in such hierarchically structured populations. We illustrate one possible application of this approach by discussing the origin and dynamics of PIG-A mutant clones that are found in the bloodstream of virtually every healthy adult human. From this it is apparent, that not only the occurrence of a mutant but also the compartment of origin is of importance. © 2011 Werner et al.

Traulsen A.,Max Planck Institute for Evolutionary Biology | Pacheco J.M.,University of Minho | Pacheco J.M.,ATP Group | Dingli D.,Mayo Medical School
Cancer Letters | Year: 2010

Mutations in oncogenes and tumor suppressor genes confer a fitness advantage to cells that can lead to cancer. The tumor phenotype normally results from the interaction of many mutant genes making it difficult to estimate the fitness advantage provided by any oncogene, except when tumors depend on one oncogene only. We utilize a model of chronic myeloid leukemia (CML), to quantitate the fitness advantage conferred by expression of BCR- ABL in hematopoietic cells from in vivo patient data. We show that BCR- ABL expression provides a high fitness advantage, which explains why this single mutation drives the chronic phase of CML. © 2010 Elsevier Ireland Ltd.

Lenaerts T.,Free University of Colombia | Lenaerts T.,Vrije Universiteit Brussel | Pacheco J.M.,University of Minho | Pacheco J.M.,ATP Group | And 2 more authors.
Haematologica | Year: 2010

Background: Tyrosine kinase inhibitors, such as imatinib, are not considered curative for chronic myeloid leukemia - regardless of the significant reduction of disease burden during treatment - since they do not affect the leukemic stem cells. However, the stochastic nature of hematopoiesis and recent clinical observations suggest that this view must be revisited. Design and Methods: We studied the natural history of a large cohort of virtual patients with chronic myeloid leukemia under tyrosine kinase inhibitor therapy using a computational model of hematopoiesis and chronic myeloid leukemia that takes into account stochastic dynamics within the hematopoietic stem and early progenitor cell pool. Results: We found that in the overwhelming majority of patients the leukemic stem cell population undergoes extinction before disease diagnosis. Hence leukemic progenitors, susceptible to tyrosine kinase inhibitor attack, are the natural target for chronic myeloid leukemia treatment. Response dynamics predicted by the model closely match data from clinical trials. We further predicted that early diagnosis together with administration of tyrosine kinase inhibitor opens the path to eradication of chronic myeloid leukemia, leading to the wash out of the aberrant progenitor cells, ameliorating the patient's condition while lowering the risk of blast transformation and drug resistance. Conclusions: Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia, although it may have to be prolonged. The depth of response increases with time in the vast majority of patients. These results illustrate the importance of stochastic effects on the dynamics of acquired hematopoietic stem cell disorders and have direct relevance for other hematopoietic stem cell-derived diseases. © 2010 Ferrata Storti Foundation.

Carlos L.D.,University of Aveiro | Pacheco J.M.,ATP group | Ferreira R.A.S.,University of Aveiro | Videira A.L.L.,GADGET
Small | Year: 2010

(Figure Presented) The emitted relaxation energy of an organic-inorganic nanohybrid upon repeated heating/cooling cycles exhibits a logarithmic time dependence (associated with hierarchically constrained dynamics), thereby providing a conspicuous fingerprint of emergent complex behavior. It is proposed that the emergence of complexity may be the rule, rather than the exception, concerning the interplay of individual and collective behavior. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

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