Biology subjects

Yubero, P.

Publications and source records attributed to Yubero, P..

6 recordsLinked to original sources

bioRxiv2024

Unveiling miR-451a and miR-142-3p as Prognostic Markers in NSCLC via sEV Liquid Biopsy

Despite advancements in personalized cancer therapies, platinum-based chemotherapy remains the cornerstone for treating solid tumors, including Non-Small Cell Lung Cancer (NSCLC). The integration of novel immunotherapies with platinum compounds has shown promising outcomes for the treatment of advanced disease. However, a significant proportion of patients experience therapeutic failure due to innate or acquired resistance. Thus, identifying molecular profiles and biomarkers to monitor patient progress and treatment response is crucial for tailoring therapeutic strategies. Small extracellular vesicle (sEV)-based liquid biopsy emerges as a promising non-invasive method for cancer management. sEVs play a critical role in cell communication and provide molecular insights into the tumor environment. In this study, we characterized the microRNome content of sEVs from cisplatin-resistant and -sensitive cancer cells using small-RNA sequencing. We identified and validated three miRNAs in two cohorts of 78 and 49 patients treated with either chemotherapy alone or chemo-immunotherapy, respectively, analyzed via liquid biopsy, differentiating NSCLC patients based on progression and overall survival. Notably, miR-451a emerged as a prognostic marker for chemo and chemo-immunotherapy, while miR-142-3p was identified for the first time as a potential prognostic marker specifically for stage IV patients, irrespective of the treatment. The combination of miR-451, miR-142-3p, and miR-55745, a novel miRNA identified from our miRNome screening, serves as a valuable biomarker for both cisplatin and chemo-immunotherapy treatment responses. This study underscores the role of sEVs in acquired cisplatin resistance and introduces novel miRNA-sEV biomarkers for managing NSCLC progression.

cancer biology↗

bioRxiv2023

Quantifying microbial guilds

The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual taxonomic groups has proven difficult despite the availability of high throughput data, hindering our understanding of such complex systems. Here, we propose a quantitative definition of guild that is readily applicable to metagenomic data. Our framework focuses on the functional character of protein sequences, as well as their diversifying nature. First, we discriminate functional sequences from the whole sequence space corresponding to a gene annotation to then quantify their contribution to the guild composition across environments. In addition, we identify and distinguish functional implementations, which are sequence spaces that have different ways of carrying out the function. We demonstrate the value of our approach with two case studies: the ammonia oxidation and polyamine uptake guilds from the Malaspina circumnavigation cruise, revealing novel ecological dynamics of the latter in marine ecosystems. Thus, the quantification of guilds helps to assess the functional role of different taxonomic groups with profound implications on the study of microbial communities.

ecology↗

bioRxiv2023

Technical upgrade of an open-source liquid handler to support bacterial colony screening

The optimization of genetically engineered biological constructs is a key step to deliver high-impact biotechnological applications. The use of high-throughput DNA assembly methods allows the construction of enough genotypic variants to successfully cover the target design space. This, however, entails extra workload for researchers during the screening stage of candidate variants. Despite the existence of commercial colony pickers, their high price excludes small research laboratories and budget-adjusted institutions from accessing such extensive screening capability. In this work we present COPICK, a technical solution to automatize colony picking in an open-source liquid handler Opentrons OT-2. COPICK relies on a mounted camera to capture images of regular Petri dishes and detect microbial colonies for automated screening. COPICKs software can then automatically select the best colonies according to different criteria (size, color and fluorescence) and execute a protocol to pick them for further analysis. Benchmark tests performed for E. coli and P. putida colonies delivers a raw picking performance over pickable colonies of 82% with an accuracy of 73.4% at an estimated rate of 240 colonies/h. These results validate the utility of COPICK, and highlight the importance of ongoing technical improvements in open-source laboratory equipment to support smaller research teams.

bioengineering↗

bioRxiv2022

The limitations of phenotype prediction in metabolism

Phenotype prediction is at the core of many questions in biology. Prediction is frequently attained by determining statistical associations between genetic and phenotypic variation, ignoring the exact processes causing the phenotype. Here, we present a framework based on genome-scale metabolic reconstructions to reveal the mechanisms behind the associations. We compute a polygenic score (PGS) that identifies a set of enzymes as predictors of growth, the phenotype. This set arises from the synergy of the functional mode of metabolism in a particular environment and its evolutionary history, and is transportable to infer the phenotype across a range of environments. We also find that there exists an optimal genetic variation for predictability and demonstrate how the linear PGS can yet explain phenotypes generated by the underlying nonlinear biochemistry. Thus, the explicit model interprets the black-box statistical associations of the genotype-to-phenotype map and helps uncover what limits prediction in metabolism.

systems biology↗

bioRxiv2021

Predicting the fitness costs of complex mutations

The fitness cost of complex pleiotropic mutations is generally difficult to assess. On the one hand, it is necessary to identify which molecular properties are directly altered by the mutation. On the other, this alteration modifies the activity of many genetic targets with uncertain consequences. Here, we examine the possibility of addressing these challenges by identifying unique predictors of these costs. To this aim, we consider mutations in the RNA polymerase (RNAP) in Escherichia coli as a model of complex mutations. Changes in RNAP modify the global program of transcriptional regulation, with many consequences. Among others is the difficulty to decouple the direct effect of the mutation from the response of the whole system to such mutation. A problem that we solve quantitatively with data of a set of constitutive genes, which better read the global program. We provide a statistical framework that incorporates the direct effects and other molecular variables linked to this program as predictors, which leads to the identification that some genes are more suitable predictors than others. Therefore, we not only identified which molecular properties best anticipate costs in fitness, but we also present the paradoxical result that, despite pleiotropy, specific genes serve as better predictors. These results have connotations for the understanding of the architecture of robustness in biological systems.

systems biology↗

bioRxiv2018

Large-scale analysis of the global transcriptional regulation of bacterial gene expression

Bacterial gene expression depends on the allocation of limited transcriptional resources provided a particular growth rate and growth condition. Early studies in a few genes suggested this global regulation to generate a unifying hyperbolic expression pattern. Here, we developed a large-scale method that generalizes these experiments to quantify the response to growth of over 700 genes that a priori do not exhibit any specific control. We distinguish a core subset following a promoter-specific hyperbolic response. Within this group, we sort genes with regard to their responsiveness to the global regulatory program to show that those with a particularly sensitive linear response are located near the origin of replication. We then find evidence that this genomic architecture is biologically significant by examining position conservation of E. coli genes in 100 bacteria. The response to the transcriptional resources of the cell results consequently in an additional feature contributing to bacterial genome organization.

systems biology↗