Biology subjects

Quesada, V.

Publications and source records attributed to Quesada, V..

4 recordsLinked to original sources

bioRxiv2026

nVenn2: faster, simpler generalized quasi-proportional Venn diagrams

Proportional Venn diagrams provide a compact representation of the relationships between sets. Each relationship is represented with a region whose area reflects the number of elements shared by a given combination of sets. This means that the number of regions grows exponentially with the number of sets, which is why proportional Venn diagrams with more than five sets are cumbersome to interpret and seldom used. However, Venn diagrams with a large number of sets may still be legible if enough regions are empty and do not need be represented. Here, we present nVenn2, the second version of the nVenn algorithm, to create quasi-proportional Venn diagrams. This new version uses a different, more flexible approach which includes steps to minimize the complexity of the diagram. Thus, computation time for nVenn2 mainly grows with the number of non-empty diagram regions, rather than with the number of sets. This property allows users to create interpretable quasi-proportional Venn diagrams with large numbers of sets. The nVenn2 algorithm is freely available as an executable program, as a web page, as an R package (nVennR2) and as a Python package (nVennPy). All interfaces allow users to edit the appearance of the resulting diagram.

bioinformatics↗

bioRxiv2025

PAN-CANCER ANALYSES IDENTIFY ONCOGENIC DRIVERS, EXPRESSION SIGNATURES, AND THERAPEUTIC VULNERABILITIES IN RHO GTPase PATHWAY GENES

RHO family GTPases are key regulators of cancer-related processes such as cytoskeletal dynamics, cell migration, proliferation, and survival. Despite this, a comprehensive understanding of RHO signaling alterations across tumors is still lacking. Here, we present a pan-cancer analysis of 484 genes encoding RHO GTPases, regulators, proximal effectors, distal downstream signaling elements, and components of their proximal interactomes using data from over 10,000 tumor samples and 33 tumor types present in The Cancer Genome Atlas (TCGA). In addition, we have utilized available data from genome-wide functional dependency screens performed in more than 1,000 gene-edited cancer cell lines. This study has uncovered positively selected mutations in both well-known and previously uncharacterized RHO pathway genes. Transcriptomic profiling reveals widespread and tumor-specific differential expression patterns, some of them correlating with copy number changes. Interestingly, certain regulators exhibit consistent expression profiles across tumors opposite to those predicted from their canonical roles. Coexpression and gene set enrichment analyses highlight coordinated transcriptional programs involving some RHO GTPase pathway genes and their linkage to key cancer hallmarks, including extracellular matrix reorganization, cell motility, cell cycle progression, cell survival, and immune modulation. Functional screens further identify context-specific dependencies on several deregulated RHO GTPase pathway genes. Altogether, this study provides a comprehensive map of RHO GTPase pathway alterations in cancer and identifies new oncogenic drivers, expression-based signatures, and therapeutic vulnerabilities that could guide future mechanistic and translational research.

cancer biology↗

bioRxiv2024

Functional conservation and divergence of Arabidopsis VENOSA4 and human SAMHD1 in DNA repair

The human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probable Arabidopsis thaliana ortholog of SAMHD1, also functions in DSB repair by HR. The ven4 loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation. Hydroxyurea, which blocks DNA replication and generates DSBs, induced VEN4 expression. The ven4 mutants were hypersensitive to hydroxyurea, with decreased DSB repair by HR. Metabolomic analysis of the strong ven4-0 mutant revealed depletion of metabolites associated with DNA damage responses. In contrast to SAMHD1, VEN4 showed no evident involvement in preventing R-loop accumulation. Our study thus reveals functional conservation in DNA repair by VEN4 and SAMHD1. One sentence summaryHuman SAMHD1 is involved in dNTP metabolism and DNA repair; the latter function is conserved in VEN4, its likely Arabidopsis ortholog.

plant biology↗

bioRxiv2023

Analysis of Arabidopsis venosa4-0 supports the role of VENOSA4 in dNTP homeostasis

An imbalance in the deoxyribonucleoside triphosphate (dNTP) pool caused by an increase or decrease in the levels of any of the four dNTPs leads to increased DNA mutations, overloading DNA repair mechanisms. The human protein SAMHD1 (Sterile alpha motif and histidine-aspartate domain containing protein 1) functions as a dNTPase to maintain the balance of the dNTP pool, as well as in DNA repair. In eukaryotes, the limiting step in de novo dNTP synthesis is catalyzed by RIBONUCLEOTIDE REDUCTASE (RNR), which consists of two R1 and two R2 subunits. In Arabidopsis, RNR1 is encoded by CRINKLED LEAVES 8 (CLS8) and RNR2 by three paralogous genes, including TSO2 (TSO MEANING UGLY IN CHINESE 2). In plants, the de novo biosynthesis of purines occurs within the chloroplast, and DOV1 (DIFFERENTIAL DEVELOPMENT OF VASCULAR ASSOCIATED CELLS 1) catalyzes the first step of this pathway. Here, to explore the role of VENOSA4 (VEN4), the most likely Arabidopsis ortholog of human SAMHD1, we studied the ven4-0 mutant. The mutant leaf phenotype caused by the ven4-0 point mutation was stronger than those of T-DNA insertional ven4 mutations. Structural predictions suggested that the E249L amino acid substitution in the mutated VEN4-0 protein rigidifies its 3D structure compared to wild-type VEN4. The morphological phenotypes of the ven4, cls8, and dov1 single mutants were similar, and those of the ven4 tso2 and ven4 dov1 double mutants were synergistic. The ven4-0 mutant had reduced levels of four amino acids related to dNTP biosynthesis, including glutamine and glycine, which are precursors in the de novo purine biosynthesis pathway. Finally, despite its annotation in some databases, At5g40290, a paralog of VEN4, is likely a pseudogene. These observations support the previously proposed role of VEN4 in dNTP metabolism. Our results reveal a high degree of cross-kingdom functional conservation between VEN4 and SAMHD1 in dNTP homeostasis.

plant biology↗