Biology subjects

Ortega-Legarreta, A.

Publications and source records attributed to Ortega-Legarreta, A..

4 recordsLinked to original sources

bioRxiv2024

GeneSetCluster 2.0: a comprehensive toolset for summarizing and integrating gene-sets analysis

BackgroundGene-Set Analysis (GSA) is commonly used to analyze high-throughput experiments. However, GSA cannot readily disentangle clusters or pathways due to redundancies in upstream knowledge bases, which hinders comprehensive exploration and interpretation of biological findings. To address this challenge, we developed GeneSetCluster, an R package designed to summarize and integrate GSA results. Over time, we and users as well identified limitations in the original version, such as difficulties in managing redundancies across multiple gene-sets, large computational times, and its lack of accessibility for users without programming expertise. ResultsWe present GeneSetCluster 2.0, a comprehensive upgrade that delivers methodological, computational, interpretative, and user-experience enhancements. Methodologically, GeneSetCluster 2.0 introduces a novel approach to address duplicated gene-sets and implements a seriation-based clustering algorithm that reorders results, aiding pattern identification. Computationally, the package is optimized for parallel processing, significantly reducing execution time. GeneSetCluster 2.0 enhances cluster annotations by associating clusters with relevant tissues and biological processes to improve biological interpretation, particularly for human and mouse data. To broaden accessibility, we have developed a user-friendly web application enabling non-programmers to use it. This version also ensures seamless integration between the R package, catering to users with programming expertise, and the web application for broader audiences. We evaluated the updates in a single-cell RNA public dataset. ConclusionGeneSetCluster 2.0 offers substantial improvements over its predecessor. Furthermore, by bridging the gap between bioinformaticians and clinicians in multidisciplinary teams, GeneSetCluster 2.0 facilitates collaborative research. The R package and web application, along with detailed installation and usage guides, are available on GitHub (https://github.com/TranslationalBioinformaticsUnit/GeneSetCluster2.0), and the web application can be accessed at https://translationalbio.shinyapps.io/genesetcluster/.

bioinformatics↗

bioRxiv2023

Unveiling the ecology, taxonomy and metabolic capabilities of MBA03, a potential key player in anaerobic digestion

Biogas, a mix of CO2, CH4 and small proportions of other gases, is a biofuel obtained by anaerobic digestion (AD). Biogas production is often considered a black box process, as the role and dynamics of some of the microorganisms involved remain undisclosed. Previous metataxonomic studies in the frame of the MICRO4BIOGAS project (www.micro4biogas.eu) revealed that MBA03, an uncharacterised and uncultured bacterial taxon, was very prevalent and abundant in industrial full-scale AD plants. Surprisingly, no culturable specimen or genome of this taxon has ever been reported, so its role in AD has remained unclear. In the present work, thirty samples derived from anaerobic digesters were sequenced, allowing the reconstruction of 108 metagenome-assembled genomes (MAGs) potentially belonging to MBA03. According to phylogenetic analyses and genomic similarity indices, MBA03 constitutes a new bacterial order, proposed as Darwinibacteriales ord. nov., which includes Darwinibacter acetoxidans gen. nov., sp. nov. of the family Darwinibacteriaceae fam. nov., along with Wallacebacter cryptica gen. nov., sp. nov. of the Wallacebacteriaceae fam. nov. Ecotaxonomic studies determined that AD processes are the main ecological niche of Darwinibacteriales. Moreover, metabolic predictions identified Darwinibacteraceae members as putative syntrophic acetate oxidising bacteria (SAOB), as they encode for the reversed Wood-Ljungdahl (W-L) pathway coupled to the glycine cleavage system. This suggests that Darwinibacteraceae members work in collaboration with hydrogenotrophic archaea to produce methane in industrial biogas plants. Overall, our findings present Darwinibacteriales as a potential key player in anaerobic digestion and pave the way towards the complete characterisation of this newly described bacterial taxa.

ecology↗

bioRxiv2023

Multivariate comparison of taxonomic, chemical and technical data from 80 full-scale an-aerobic digester-related systems

This study represents one of the most comprehensive characterisations of the anaerobic digestion (AD) microbiome with 80 samples from 45 different large-scale reactors in three coun-tries. Technical, chemical and taxonomic data was thoroughly collected, analyzed and correlated to identify the main drivers of AD processes. Our results showed that MBA03, Proteiniphilum, a member of Dethiobacteraceae, and Caldicoprobacter were present in all the samples, while Meth-anosarcina was the most abundant and prevalent archaea. Two distinct bacterial clusters were iden-tified by correlating microbial abundances. One was correlated with hydrogenotrophic and the other with acetoclastic methanogenesis. Organic acids, ammonia, nitrogen, COD and the trace el-ements Fe, Mo, and the macro nutrient P had the greatest impact on AD microbiomes. Temperature, reactor type and substrate also influenced the formation of a specialized microbial community. Overall, this work sheds light on the microbial key players involved in AD and evaluates how they are affected by technical and chemical parameters. HighlightsO_LIGeneration of a holistic dataset of chemical, taxonomic and technical parameters of 80 large-scale anaerobic digestion systems. C_LIO_LIIdentification of a core microbiome comprising MBA03, Proteiniphilum, an uncultured or-ganism from the Dethiobacteraceae family, and the Caldicoprobacter family. C_LIO_LIIdentification of the main influencing parameters that determine the occurrence and non-occurrence of specific genera. C_LIO_LICorrelation of bacterial taxa with hydrogenotrophic and/or acetoclastic archaea. C_LI

microbiology↗

bioRxiv2023

Uncovering the cis-regulatory program of early human B-cell commitment and its implications in the pathogenesis of B-cell acute lymphoblastic leukemia

Dysregulation of the early stages of B-cell lymphopoiesis, orchestrating the development of cellular immunity, may induce malignant transformations. Therefore, it is essential to characterize the gene regulatory network (GRN) driving B-cell lymphopoiesis in healthy individuals to uncover malignancy mechanisms. To this end, we generated a dataset that included paired human data for chromatin accessibility and gene expression in eight B-cell precursor stages, providing the first deep characterization of early B-cell lymphopoiesis, including the identification of regulatory elements and the reconstruction of the GRN. Using this data, we recapitulated well-known regulatory elements and revealed new regulons, such as ELK3, enriched in pro-B cells with a putative role in cell cycle progression. Moreover, a single-cell multi-omics analysis validated and enhanced the resolution of the regulatory landscape recovered by bulk data, revealing MYBL2 and ZNF367 as specific regulons of cycling cell states, and CEBPA associated with lymphoid multipotent progenitors (LMPPs). Importantly, this dataset enabled us to uncover B-cell acute lymphoblastic leukemia (B-ALL) triggers. We identified different cellular origins of malignant transformation depending on the B-ALL subtype, including the association of the ETV6-RUNX1 with pro-B cells and the increased expression of ELK3 in this ALL subtype. Overall, our dataset provides the most comprehensive atlas to date of early human B-cell regulation (B-rex; https://translationalbio.shinyapps.io/brex/), facilitating further understanding of B-cell differentiation in health and disease.

immunology↗