Biology subjects

Le Cunff, Y.

Publications and source records attributed to Le Cunff, Y..

4 recordsLinked to original sources

bioRxiv2024

Modeling the emergent metabolic potential of soil microbiomes in Atacama landscapes

Soil microbiomes harbor complex communities and exhibit important ecological roles resulting from biochemical transformations and microbial interactions. Difficulties in characterizing the mechanisms and consequences of such interactions together with the multidimensionality of niches hinder our understanding of these ecosystems. The Atacama Desert is an extreme environment that includes unique combinations of stressful abiotic factors affecting microbial life. In particular, the Talabre Lejia transect has been proposed as a unique natural laboratory for understanding adaptation mechanisms. We propose a systems biology-based computational framework for the reconstruction and simulation of community-wide and genome-resolved metabolic models, in order to provide an overview of the metabolic potential as a proxy of how microbial communities are prepared to respond to the environment. Through a multifaceted approach that includes taxonomic and functional profiling of microbiomes, simulation of the metabolic potential, and multivariate analyses, we were able to identify key species and functions from six contrasting soil samples across the Talabre Lejia transect. We highlight the functional redundancy of whole metagenomes, which act as a gene reservoir from which site-specific functions emerge at the species level. We also link the physicochemistry from the puna and the lagoon samples to specific metabolic machineries that could be associated with their adaptation to the unique environmental conditions found there. We further provide an abstraction of community composition and structure for each site that allows to describe them as sensitive or resilient to environmental shifts through putative cooperation events. Our results show that the study of community-wide and genome-resolved metabolic potential, together with targeted modeling, may help to elucidate the role of producible metabolites in the adaptation of microbial communities. Our framework was designed to handle non-model microorganisms, making it suitable for any (meta)genomic dataset that includes nucleotide sequence data and high-quality environmental metadata for different samples.

systems biology↗

bioRxiv2024

SPARTA: Interpretable functional classification of microbiomes and detection of hidden cumulative effects.

The composition of the gut microbiota is a known factor in various diseases, and has proven to be a strong basis for automatic classification of disease state. A need for a better understanding of this community on the functional scale has since been voiced, as it would enhance these approaches biological interpretability. In this paper, we have developed a computational pipeline for integrating the functional annotation of the gut microbiota to an automatic classification process, and facilitating downstream interpretation of its results. The process takes as input taxonomic composition data (such as tables of Operational Taxonomic Unit (OTU) or Amplicon Sequence Variant (ASV) abundances), and links each component to its functional annotations through interrogation of the UniProt database. A functional profile of the gut microbiota is built from this basis. Both profiles, microbial and functional, are used to train Random Forest classifiers to discern unhealthy from control samples. An automatic variable selection is then performed on the basis of variable importance, and the method can be iterated until classification performances diminish. This process shows that the translation of the microbiota into functional profiles gives comparable, albeit slightly inferior performances when compared to microbial profiles. Through repetition, it also outputs a robust subset of discriminant variables. These selections were shown to be more reliable than those obtained by a state of the art method, and its contents were validated through a manual bibliographic research. The interconnections between selected OTUs and functional annotations were also analyzed, and revealed that important annotations emerge from the cumulated influence of non-selected OTUs.

bioinformatics↗

bioRxiv2023

Only three principal components account for inter-embryo variability of the spindle length over time.

How to quantify inter-individual variability? When measuring many features per experiment/individual, this question becomes non-trivial. One challenge lies in choosing features to recapitulate high-dimensional data. This paper focuses on spindle elongation phenotypes to highlight how a data-driven approach can help tackle this challenge. We showed that only three typical elongation patterns describe spindle elongation in C. elegans one-cell embryo. We called them archetypes. These archetypes were automatically extracted from the experimental data using principal component analysis (PCA) rather than defined a priori. They accounted for more than 95% of inter-individual variability in a dataset of more than 1600 experiments across more than 100 different experimental conditions (RNAi, mutants, changes in temperature, etc.). The two first archetypes were consistent with standard measures in the field, namely the average spindle length and the spindle elongation rate in late metaphase and anaphase. However, our archetypes were not strictly corresponding to these classic, manually-set, features. The third archetype, accounting for 6% of the variability, was novel and corresponded to a transient spindle shortening in late metaphase. We revealed that it is part of spindle elongation dynamics in all conditions. It is reminiscent of the spindle elongation pattern observed upon kinetochore function defects. Interestingly, because these archetypes were all three present from metaphase on, it implied that spindle elongation around the anaphase onset is sufficient to predict its late anaphase length. We validated this idea using a machine-learning approach. The inter-individual differences between embryos depleted from cell division-related proteins have the same underlying nature as inter-individual differences naturally arising between wild-type embryos. The same conclusion holds also when analysing embryos dividing at various temperatures. We thus propose that beyond the apparent complexity of the spindle and variability in the phenotypes of various gene depletions, only three independent mechanisms account for spindle elongation, weighted differently in the various conditions; meanwhile, no mechanism is specific to any condition. As such, given amounts of these three archetypes could represent a quantitative phenotype.

bioinformatics↗

bioRxiv2019

Two dynamical behaviours of the microtubules at cell cortex reveal pulling and pushing forces that position the spindle in C. elegans embryo.

In the Caenorhabditis elegans zygote, astral microtubules generate forces, pushing against and pulling from the cell periphery. They are essential to position the mitotic spindle. By measuring the dynamics of astral microtubules at the cortex, we revealed the presence of two populations, residing there for 0.4 s and 1.8 s, which correspond to the pulling and pushing events, respectively. Such an experiment offers a unique opportunity to monitor both forces that position the spindle under physiological conditions and study their variations along the anteroposterior axis (space) and the mitotic progression (time). By investigating pulling-force-generating events at the microscopic level, we showed that an anteroposterior asymmetry in dynein on-rate - encoding pulling-force imbalance - is sufficient to cause posterior spindle displacement. The regulation by spindle position - reflecting the number of microtubule contacts in the posterior-most region - reinforces this imbalance only in late-anaphase. Furthermore, we exhibited the first direct proof that the force-generator increasing persistence to pull (processivity) accounts for the temporal control of pulling force throughout mitosis. We thus propose a three-fold control of pulling force, by the polarity, spindle position and mitotic progression. Focusing on pushing force, we discovered a correlation between its density and the stability of the spindle position during metaphase, which strongly suggests that the pushing force contributes to maintaining the spindle at the cell centre. This force remains constant and symmetric along the anteroposterior axis during the division. The pulling one increases in intensity and becomes dominant at anaphase. In conclusion, the two-population study enabled us to decipher the complex regulation of the spindle positioning during cell division.

biophysics↗