Biology subjects

Barrantes, I.

Publications and source records attributed to Barrantes, I..

4 recordsLinked to original sources

bioRxiv2025

Meta-analysis reveals reproducible rapamycin-induced shifts in the mouse gut microbiome

Rapamycin is a geroprotective compound that extends lifespan and is well characterised in systemic physiology. However, due to heterogeneous methodologies, its effects on the gut microbiome, an emerging regulator of ageing and health, remain poorly defined. Here, we systematically assessed these effects in mice using a harmonised meta-analysis workflow, reprocessing raw sequence data end-to-end. We conducted a harmonised meta-analysis of the gut microbiome using 16S rRNA gene amplicon data from three independent mouse studies (n = 54) spanning dietary and intraperitoneal rapamycin interventions with matched controls. All samples were uniformly processed using a standardised 16S rRNA bioinformatics workflow. Genus-level abundances were modelled using two complementary approaches: a per-study zero-inflated beta modelling framework with random-effects meta-analysis, and a batch-corrected linear modelling framework incorporating correction prior to meta-analysis. Dose-response meta-regression assessed whether rapamycin-associated changes scaled with dose (42-990 mg/kg), integrating presence and magnitude of effects across heterogeneous study designs. Rapamycin treatment induced reproducible shifts in specific taxa across studies, with a subset of core responders consistently altered regardless of dose. Among the core responders, Bacteroides increased (OR = 1.59, q = 0.042) and Muribaculum decreased (OR = 0.55, q = 0.042), each significant in both frameworks. Whereas Ruminococcus decreased (OR = 0.60, q = 0.089), it was significant in the batch-corrected framework, but only a trend in zero-inflated modelling. Dose-sensitivity analyses highlighted Lachnospiraceae as the most consistent dose-sensitive taxon, with other associations largely restricted to extreme doses. Functional pathway analysis revealed alterations in energy metabolism and microbial stress response. This harmonised meta-analysis highlights notable shifts in the gut microbiome connected to rapamycin across the examined studies, outlining potential core microbial signatures. These findings were observed within heterogeneous experimental contexts, and further validation in additional studies will be needed to confirm their generality.

microbiology↗

bioRxiv2022

Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data

The highest risk factor for chronic diseases is chronological age, and age-related chronic diseases account for the majority of deaths worldwide. Targeting senescent cells that accumulate in disease-related tissues presents a strategy to reduce disease burden and to increase healthspan. Our goal was the computational identification of senotherapeutic repurposing candidates that potentially eliminate senescent cells, based on their similarity in gene expression effects to dasatinib, a tyrosine-kinase inhibitor that induces apoptosis in certain senescent cell types, and that is frequently used as a senolytic together with quercetin. The natural senolytic piperlongumine (a compound found in long pepper), and the natural senomorphics parthenolide, phloretin and curcumin (found in various edible plants) were identified as potential substitutes of dasatinib. The gene expression changes underlying the repositioning highlight apoptosis-related genes and pathways. The four compounds, and in particular the top-runner piperlongumine, may be combined with quercetin to obtain natural formulas emulating the dasatinib + quercetin (D+Q) formula that is frequently used in clinical trials targeting senescent cells.

bioinformatics↗

bioRxiv2018

Pathway maps enable straightforward yet customized and semi-automated yet insightful analyses of omics data

To explore the molecular processes underlying some biological theme of interest based on public data, gene lists are used herein as input for the construction of annotated pathway maps, employing Cytoscape apps, and then high-throughput (\"omics\") gene expression data are overlaid onto these maps. Seeded with a published set of marker genes of the senescence-associated secretory phenotype and the genes of the cellular senescence KEGG pathway, a gene/protein interaction network and annotated clusters (a \"pathway map\") of cellular senescence are derived. The map can be amended, by adding some application-specific genes, and overlaid with gene expression data describing cellular senescence of fibroblasts and with disease-related gene expression data associated with prostate and pancreatic cancer, and with ischemic stroke, allowing insights into the role of cellular senescence in disease. Some gene expression data are derived from the \"Biomarker Benchmark repository\". The pathway map approach can be followed in principle for any biological theme of interest, fostering much-needed independence from the investigator-biased expert networks usually used for overlaying gene expression data.

genomics↗

bioRxiv2018

Healthspan pathway maps in C. elegans and humans highlight transcription, prolifera-tion/biosynthesis and lipids

The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. However, a precise definition of health and healthspan is not straightforward, and the causal molecular basis of health \"per se\" is largely unknown. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans, featuring the themes transcription initiation, proliferation and cholesterol/lipid processing, and for C. elegans, featuring the themes immune response, mitochondrion and biosynthesis based on genetic and compound intervention data, and lipids, biosynthesis and transcription based on WormBase compound intervention data. Overlaying healthspan-related gene expression data (describing effects of metabolic intervention associated with improvements in health) onto the aforementioned healthspan pathway maps, we observe the downregulation of Notch signalling in humans and of proliferation/cell-cycle in C. elegans. The former reflects the proinflammatory role of the Notch pathway. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, is available as a reference for future investigations, at http://www.h2020awe.eu/index.php/pathways/.

bioinformatics↗