Biology subjects

Tello, D.

Publications and source records attributed to Tello, D..

4 recordsLinked to original sources

bioRxiv2026

Anonymized Somatic Tumor Twins (STTs) enable open genome data sharing and use in research and clinical oncology

The study of somatic variants from tumor genomes is fundamental to cancer research and clinical decision-making. However, existing data protection frameworks impose restrictions on the use and sharing of these variants in conjunction with sensitive germline information. To overcome these challenges, we developed GenomeAnonymizer, the first method to anonymize short-read DNA sequences from tumor-normal pairs. This generates Somatic Tumor Twins (STTs), an anonymized version of the original data that preserves the donors privacy while retaining somatic tumor information and sequencing noise. This method successfully removed all detectable germline variants from the 47 PCAWG-Pilot samples. We further demonstrate that Whole-Genome Sequencing (WGS) STTs preserve more than 98% of the original somatic variants, enabling reliable downstream analysis that replicates somatic-related findings from the original samples, including cancer driver genes, mutational signatures, and intratumor heterogeneity. Importantly, we also show that STTs can reproduce the identification of actionable genes and downstream clinical interpretations and decision-making. We generated a cancer cohort of STTs matched with synthetic clinical data that could be openly shared and used across projects and centers worldwide. This paradigm-shifting approach will accelerate discovery and clinical translation in oncology and enable the robust benchmarking of genome analysis and large-scale data infrastructures.

bioinformatics↗

bioRxiv2023

Graphlet-based hyperbolic embeddings capture evolutionary dynamics in genetic networks

MotivationSpatial Analysis of Functional Enrichment (SAFE) is a popular tool for biologists to investigate the functional organisation of biological networks via highly intuitive 2D functional maps. To create these maps, SAFE uses Spring embedding to project a given network into a 2D space in which nodes connected in the network are near each other in space. However, many biological networks are scale-free, containing highly connected hub nodes. Because Spring embedding fails to separate hub nodes, it provides uninformative embeddings that resemble a "hairball". In addition, Spring embedding only captures direct node connectivity in the network and does not consider higher-order node wiring patterns, which are best captured by graphlets, small, connected, non-isomorphic, induced subgraphs. The scale-free structure of biological networks is hypothesised to stem from an underlying low-dimensional hyperbolic geometry, which novel hyperbolic embedding methods try to uncover. These include coalescent embedding, which projects a network onto a 2D disk. ResultsTo better capture the functional organisation of scale-free biological networks, whilst also going beyond simple direct connectivity patterns, we introduce Graphlet Coalescent (GraCoal) embedding, which embeds nodes nearby on a hyperbolic disk if they tend to touch a given graphlet together. We use GraCoal embedding to extend SAFE. Through SAFE-enabled enrichment analysis, we show that GraCoal embeddings captures the functional organisation of the genetic interaction networks of fruit fly, budding yeast, fission yeast and E. coli better than graphlet-based Spring embedding. We show that depending on the underlying graphlet, GraCoal embeddings capture different topology-function relationships. We show that triangle-based GraCoal embedding captures functional redundancy between paralogous genes. Availabilityhttps://gitlab.bsc.es/dtello/graphlet-based-SAFE Contactnatasha@bsc.as Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2022

NGSEP 4: Efficient and Accurate Identification of Orthogroups and Whole Genome Alignment

Whole-genome alignment allows researchers to understand the genomic structure and variations among the genomes. Approaches based on direct pairwise comparisons of DNA sequences require large computational capacities. As a consequence, pipelines combining tools for orthologous gene identification and synteny have been developed. In this manuscript, we present the latest functionalities implemented in NGSEP 4, to identify orthogroups and perform whole genome alignments. NGSEP implements functionalities for identification of clusters of homologus genes, synteny analysis and whole genome alignment, and visualization. Our results showed that the NGSEP algorithm for ortholog identification has competitive accuracy and better efficiency in comparison to commonly used tools. The implementation also includes a visualization of the whole genome alignment based on synteny of the orthogroups that were identified, and a reconstruction of the pangenome based on frequencies of the orthogroups among the genomes. Finally, our software includes a new graphical user interface. We expect that these new developments will be very useful for several studies in evolutionary biology and population genomics.

bioinformatics↗

bioRxiv2018

Mitochondrial Na+ import controls oxidative phosphorylation and hypoxic redox signalling

All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1-4, and both phenomena occur in hypoxia4-8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism.

biochemistry↗