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Integrative biology in the discovery of relevant biomarkers monitoring cognitive disorders pathogenesis and progression

La biologie intégrative dans la découverte de biomarqueurs spécifiques au suivi de la pathogénèse de désordres cognitifs et leur évolution

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Bio Tribune Magazine

Abstract

Cognitive disorders are highly heterogeneous in terms of symptoms, clinical aetiologies, disease progression and therapeutic responses. Furthermore, their potential biological causes remain largely unknown. Progress at these different levels is currently mired in a vicious circle. The identification of coherent biomarkers, essential for clinical and therapeutic progress, requires an understanding of either the relevant pathogenic processes or, at the very least, of the parameters that need to be monitored. But, syndrome-dominated conceptual thinking has become a barrier to understanding the biological processes linked to diseases characterized by clinical and therapeutic heterogeneity. As a result, current biomarkers of cognitive disorders are much too numerous, too heterogeneous and too variable to serve useful purposes. This leads to an untenable situation that precludes coherent therapeutic developments since it effectively prevents defining what could constitute valid biological, clinical and therapeutic approaches. How to escape from this situation? The problem could be partly resolved by adopting the much wider views allowed by “system-wide” approaches: indeed, by constructing predictive theoretical models of what could constitute pathological cognitive processes. This, naturally, shall require the integration of massive amounts of highly heterogeneous and often conflicting information. The following article aims to provide a necessarily brief overview of the concepts, the breadth of data and the variety of network dynamics that will have to be considered while proposing a functional modelbuilding approach, experimentally validated in vitro and in vivo, that could be fruitfully utilised.

Résumé

Les désordres cognitifs sont caractérisés par une extrême hétérogénéité en termes de symptômes, de présentation clinique, de progression pathologique et de réponses thérapeutiques. De plus, leurs causes restent très largement inconnues. Aujourd’hui, les progrès dans ces différents domaines sont embourbés dans un cercle vicieux. L’identification de biomarqueurs cohérents, essentiels à tout progrès clinique et thérapeutique, requiert, sinon une compréhension des processus pathogéniques, à tout le moins une identification des paramètres qui devront faire l’objet d’un suivi dans un cadre défini. Mais les approches conceptuelles, aujourd’hui largement dominées par la « syndromologie » sont de fait devenues des barrières à la compréhension des processus biologiques liés aux maladies caractérisées par une hétérogénéité clinique et thérapeutique. II en résulte que les biomarqueurs disponibles dans le domaine des maladies cognitives sont bien trop nombreux, trop hétérogènes et trop variables pour être utiles. Ceci entraîne une situation intenable où tout développement thérapeutique cohérent est très largement compromis par le fait qu’il devient impossible de définir ce qui pourrait constituer des approches biologiques, cliniques et thérapeutiques valides. Comment échapper à cette situation ? Le problème pourrait être en partie résolu par l’adoption de la vision très large que permettent les approches systémiques. En d’autres termes, par la construction de modèles théoriques prédictifs représentant des mécanismes pouvant constituer des processus cognitifs pathologiques. Pour ce faire, il sera bien entendu nécessaire d’intégrer des masses énormes d’informations souvent contradictoires. Le présent article a pour but de dresser un inventaire nécessairement succinct des concepts, de la diversité de données et des dynamiques de réseaux qui devront être prises en compte tout en proposant une méthode fonctionnelle de modélisation, validée expérimentalement in vitro et in vivo, qui pourrait être ici mise à profit.

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  1. Bio-Modeling Systems, 26, rue Saint-Lambert, 75015, Paris, France

    F. Iris, M. Gea, P. -H. Lampe, G. Dine & P. Santamaria

  2. Institut Biotechnologique de Troyes, 11, rue Marie Curie, 10000, Troyes, France

    G. Dine

  3. Formitel, 3, rue de l’Arrivée, 75015, Paris, France

    P. Santamaria

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Iris, F., Gea, M., Lampe, P.H. et al. Integrative biology in the discovery of relevant biomarkers monitoring cognitive disorders pathogenesis and progression. Bio trib. mag. 28, 8–23 (2008). https://doi.org/10.1007/BF03001641

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