Biology subjects

Calle-Espinosa, J.

Publications and source records attributed to Calle-Espinosa, J..

3 recordsLinked to original sources

bioRxiv2025

Stability and diversity of interactions in complex microbiomes

Complex microbial communities abound in nature, yet designing robust and stable microbial consortia for use in biotechnology and One Health applications remains a major challenge. Inspired by a large body of work on community ecology, we used mathematical models to investigate what makes a microbiome stable. Our approach integrates three factors that characterize many free-living and host-associated microbial communities but have seldom been jointly considered: sustained growth, high-order interactions, and a broad diversity of interaction profiles. We derived a simple expression that relates community stability to basic statistical properties of the underlying interaction networks. Analytical and numerical results show that synergistic high-order interactions, such as those derived from complex auxotrophies, play a critical role in stabilizing species-rich microbial communities with highly diverse interaction profiles. In contrast, in the absence of high-order interactions, viability is restricted to communities with very sparse or fully mutualistic interaction networks. Our findings have the potential to inform microorganism-based interventions in areas in which sustained growth and long-term stability are desirable properties. We propose that incorporating high-order mutualism into engineered microbial consortia could improve their robustness by buffering design uncertainty about the underlying interaction networks.

ecology↗

bioRxiv2022

Pervasive conditional selection of driver mutations and modular epistasis networks in cancer

Cancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We developed a method to quantify COnditional SELection on the Excess of Nonsynonymous Substitutions (Coselens) in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identified 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario, where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.

cancer biology↗

bioRxiv2017

A genome-scale study of metabolic complementation in endosymbiotic consortia: the case of the cedar aphid

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism -which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca. Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome scale metabolic network (GEM) for the bacterial consortium from the cedar aphid iBSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e. tryptophan and biotin biosynthesis) and the proposal of a hitherto unnoticed event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with iBSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is more significant than previously thought.

systems biology↗