Biology subjects

Saavedra, C.

Publications and source records attributed to Saavedra, C..

7 recordsLinked to original sources

bioRxiv2026

Beyond a single threshold: calibration of CADD v1.7 and AlphaGenome for ACMG/AMP computational evidence across variant classes, model versions, and reference data

Clinical laboratories use computational predictors as supporting evidence for or against pathogenicity under the ACMG/AMP guidelines, but this evidence is reliable only when score thresholds are calibrated. Genome-wide predictors such as CADD are often applied using a single cutoff across all variant types and model versions, and the new AlphaGenome Variant Impact score (AVI) has not been calibrated. Following a prespecified plan and the ClinGen calibration method, we calibrated CADD v1.7 and AVI on rare ClinVar missense variants. Both predictors provided moderate evidence of pathogenicity and strong evidence of benignity, and their thresholds held for variants classified after calibration. AVI performed better than CADD in each comparison and approached the missense-specific predictors. Thresholds available in 2024 gave AVI evidence in the final direction for 72.5% of the variants of uncertain significance (VUS) resolved by 2026, compared with 60.5% for CADD. Applied to 1.2 million current missense VUS, the calibrated predictors agreed on pathogenic or benign evidence for four in ten, and on strong pathogenic evidence for 186 VUS reviewed by expert panels, which can be reassessed first. Outside missense variants, the same thresholds failed, producing false-benign evidence for pathogenic noncoding variants. A change in CADD version altered the evidence level for a third of variants without improving discrimination. Our results suggest that computational evidence is most reliable within the variant class and model version in which it was calibrated. In practice, laboratories may prioritize missense-specific predictors, use AVI when a genome-wide predictor is needed, and reassess thresholds after model updates.

genetics↗

bioRxiv2026

The biogeography of the stripped Venus clam, Chamelea gallina, in the Mediterranean Sea indicates limited gene flow and shows evidence of local adaptation.

AimTo assess how biogeographic barriers and environmental heterogeneity shape connectivity and local adaptation in the striped Venus clam (Chamelea gallina), a commercially exploited bivalve in the Mediterranean Sea. LocationNortheast Atlantic (Gulf of Cadiz) and Mediterranean Sea (Alboran, Balearic, Tyrrhenian and Adriatic regions). TaxonChamelea gallina (Bivalvia: Veneridae). MethodsWe analysed genome-wide single nucleotide polymorphisms (SNPs) from 226 individuals sampled across six regions (Gulf of Cadiz, Alboran Sea, Balearic Sea, Ebro Delta, Tyrrhenian Sea and Adriatic Sea) using a seascape genomic framework. Population structure was inferred using both putatively neutral and adaptive loci. Genotype-environment associations were tested against key oceanographic variables, including sea surface temperature, salinity and nutrient availability. ResultsNeutral loci revealed weak genetic differentiation, consistent with substantial gene flow across most of the species range. In contrast, putatively adaptive loci uncovered pronounced genetic structure that corresponded closely to major Mediterranean biogeographic regions, particularly the Adriatic Sea, the Gulf of Cadiz and western-central Mediterranean basins. Significant associations were detected between genetic variation and environmental gardients, with several candidate adaptive SNPs located within coding regions, suggesting functional responses to spatially heterogeneous conditions. Main conclusionsOur results demonstrate that local adaptation can generate biologically meaningful population structure in C. gallina despite high levels of connectivity inferred from neutral markers. This decoupling between neutral and adaptive variation highlights the importance of integrating adaptive genomic information into biogeographic inference. Recognizing environmentally driven genetic differentiation is essential for defining robust management units and for improving the long-term sustainability and resilience of C. gallina fisheries under increasing anthropogenic pressure and climate change.

evolutionary biology↗

bioRxiv2025

Temporal seascape genomics identifies evolutionary significant units in a highly exploited marine resource, the wedge clam Donax trunculus.

Clam fisheries along the Spanish coast have declined unevenly, while stock management often follows political rather than biological boundaries. To inform conservation and fishery management, this study used temporal seascape genomics to assess population structure, genetic diversity and effective population size (Ne) in the wedge clam Donax trunculus across approximately 2,000 km of the Iberian coast. Using 7,830 putatively neutral and 649 candidate outlier SNPs from 331 individuals, the analyses confirmed broad Atlantic-Mediterranean differentiation, identified the Alboran Sea as a distinct genetic unit, and revealed finer-scale Atlantic substructure. Temporal genomic comparisons showed that population structure remained largely stable over the study period, although genetic diversity changed in a site-specific manner across fishing areas. Genotype-environment analyses indicated that spatial structure explained more genomic variation than environmental predictors, especially after accounting for spatial- environmental collinearity. Overall, the results show that temporal seascape genomics can distinguish persistent biogeographic structure from short-term, local genomic change in exploited marine invertebrates, providing a robust framework for biologically informed stock delineation. The genetically distinct groups identified here should therefore be considered separately in conservation, fishery management and any future reinforcement planning.

evolutionary biology↗

bioRxiv2023

Transcriptional profiling of populations in the clam Ruditapes decussatus suggests genetically determined differentiation in gene-expression along parallel temperature gradients and between races of the Atlantic Ocean and West Mediterranean sea

Ongoing ocean warming due to climate change poses new challenges for marine life and its exploitation. We have used transcriptomics to find genetically-based responses to increased temperature in natural populations of the marine clam Ruditapes decussatus living along parallel thermal gradients in southern Europe. Clams of the Atlantic and West Mediterranean races were collected in a northern (cool) and a southern (warm) localities. The animals were kept in running seawater in the warm, Atlantic southern locality for a 15-week period, during which water temperature raised to typical southern European summer values. After this period, the expression profile was obtained for a total of 34 clams and 11,025 probes by means of an oligonucleotide microarray. We found distinct transcriptional patterns for each population based on a total of 553 differentially expressed genes (DEG), indicating innate differences which probably have a genetic basis. Race and latitude contributed significantly to gene expression differences, with very different sets of DEG. A gene ontology analysis showed that races differed mainly at genes involved in ribosomal function and protein biosynthesis, while genes related to glutathione metabolism and ATP synthesis in the mitochondria were the most outstanding as to north/south transcriptional differences.

genomics↗

bioRxiv2023

Label-free observation of individual solution phase molecules

The vast majority of chemistry and biology occurs in solution, and new label-free analytical techniques that can help resolve solution-phase complexity at the single-molecule level can provide new microscopic perspectives of unprecedented detail. Here, we use the increased light-molecule interactions in high-finesse fiber Fabry-Perot microcavities to detect individual biomolecules as small as 1.2 kDa with signal-to-noise ratios >100, even as the molecules are freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of sub-populations in mixed samples. Strikingly, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight can also be resolved. Detection is based on a novel molecular velocity filtering and dynamic thermal priming mechanism leveraging both photo-thermal bistability and Pound-Drever-Hall cavity locking. This technology holds broad potential for applications in life and chemical sciences and represents a major advancement in label-free in vitro single-molecule techniques.

biophysics↗

bioRxiv2021

Feeding ecology of broadbill swordfish (Xiphias gladius) in the California Current

The feeding ecology of broadbill swordfish (Xiphias gladius) in the California Current was described based on analysis of stomach contents collected by federal fishery observers aboard commercial drift gillnet boats from 2007 to 2014. Prey were identified to the lowest taxonomic level and diet composition was analyzed using univariate and multivariate methods. Of 299 swordfish sampled (74 to 245 cm eye-to-fork length), 292 non-empty stomachs contained remains from 60 prey taxa. Diet consisted mainly of cephalopods but also included epipelagic and mesopelagic teleosts. Jumbo squid (Dosidicus gigas) and Gonatopsis borealis were the most important prey based on the geometric index of importance. Swordfish diet varied with body size, location and year. Jumbo squid, Gonatus spp. and Pacific hake (Merluccius productus) were more important for larger swordfish, reflecting the ability of larger specimens to catch large prey. Jumbo squid, Gonatus spp. and market squid (Doryteuthis opalescens) were more important in swordfish diet in inshore waters, while G. borealis and Pacific hake predominated offshore. Jumbo squid was more important from 2007-2010 than in 2011-2014, with Pacific hake the most important prey item in the latter period. Diet variation by area and year probably reflects differences in swordfish preference, prey availability, prey distribution, and prey abundance. The range expansion of jumbo squid that occurred during the first decade of this century may particularly explain their prominence in swordfish diet from 2007-2010. Some factors that may influence dietary variation in swordfish were identified. Standardization could make future studies more comparable for conservation monitoring purposes.

ecology↗

bioRxiv2020

AAV Ablates Neurogenesis in the Adult Murine Hippocampus

Recombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hours post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentate gyrus (DG)--without ablating adult neurogenesis--can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo 2-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system (CNS) should be carefully evaluated.

neuroscience↗