Biology subjects

Garcia-Valiente, R.

Publications and source records attributed to Garcia-Valiente, R..

4 recordsLinked to original sources

bioRxiv2026

AbSolution: interactive exploration of sequence-derived features in AIRR-seq repertoires

High-throughput sequencing of B-cell and T-cell immune receptor repertoires provides unprecedented insight into adaptive immune responses. The data produced are structured by clonal relationships and somatic mutation signatures, and yield extremely rich information in sequence-derived features, including physicochemical properties and compositional patterns. However, integrated analysis across datasets, conditions, and time points remains challenging. Current analytical tools typically focus only on certain features within individual repertoires, without enabling integrated, multivariable comparisons across datasets, conditions, and time points to address their diversity and variability. Here we present AbSolution, a user-friendly and flexible interactive application for comprehensive exploration of immune repertoires and their sequence-based properties. AbSolution enables multiscale analysis of thousands of sequence-derived features across receptor regions, while accounting for V(D)J usage, clonal composition and experimental groupings. We demonstrate its utility by identifying distinct sequence-based profiles associated with dominant (highly abundant) and non-dominant B-cell clones in peripheral blood BCR repertoires from patients with idiopathic inflammatory myopathies, and with antigen-responsive T-cell populations over time in a longitudinal in vitro antigen-stimulation dataset. Through interactive, interlinked visualizations, statistical feature selection and multi-sample comparisons, AbSolution facilitates integrated feature profiling that supports the interpretation of immune selection processes and enables systematic analysis of complex repertoire datasets.

bioinformatics↗

bioRxiv2026

AbSolution and ENCORE: a proof-of-concept for automating computational reproducibility in interactive applications

Reproducibility and transparency in computational analyses are essential in science, although achieving these goals often requires significant knowledge and systematic organization. Graphical interactive applications simplify the conduct of analyses and make them accessible to a broader audience. However, there is currently no consensus on how to and to which extent implement reproducibility in interactive applications. We recently developed AbSolution, a user-friendly and flexible interactive web-based R Shiny application for exploring immune repertoires and their sequence-based features, and we established the ENCORE framework to enhance transparency and reproducibility by guiding researchers in structuring and documenting computational projects. In this work, as a proof-of-concept we integrate AbSolution, ENCORE and specific R packages to address reproducibility challenges. This enables a single-step export of raw, processed, and meta-data, the software environment, the underlying generated code and a HTML report containing results and figures, operating system, hardware and R session details, and researcher notes. Its reproducibility has been independently validated by the CODECHECK initiative. This paper demonstrates how the combination of several approaches can improve and automate reproducibility of interactive applications.

bioinformatics↗

bioRxiv2020

A missense in HSF2BP causing Primary Ovarian Insufficiency affects meiotic recombination by its novel interactor C19ORF57/MIDAP

Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with 3 cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse, compared to a new HSF2BP knock-out mouse showed that it behaves as a hypomorphic allele. HSF2BP-S167L females show reduced fertility with small litter sizes. To obtain mechanistic insights, we identified C19ORF57/MIDAP as a strong interactor and stabilizer of HSF2BP by forming a higher-order macromolecular structure involving BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L mutation showed a strongly decreased expression of both MIDAP and HSF2BP at the recombination nodules. Although HSF2BP-S167L does not affect heterodimerization between HSF2BP and MIDAP, it promotes a lower expression of both proteins and a less proficient activity in replacing RPA by the recombinases RAD51/DMC1, thus leading to a lower frequency of cross-overs. Our results provide insights into the molecular mechanism of two novel actors of meiosis underlying non-syndromic ovarian insufficiency. SummaryFelipe-Medina et al. describe a missense variant in the meiotic gene HSF2BP in a consanguineous family with Premature Ovarian Insufficiency, and characterize it as an hypormorphic allele, that in vivo impairs its dimerization with a novel meiotic actor, MIDAP/ C19ORF57, and affect recombination at double-strand DNA breaks.

genetics↗

bioRxiv2018

Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit

Meiotic recombination generates crossovers which are essential to ensure genome haploidization. The ubiquitin proteasome system regulates meiotic recombination through its association to the synaptonemal complex, a zipper-like structure that holds homologs and provides the structural framework for meiotic recombination. Here we show that the testis-specific 4s subunit (PSMA8) of the spermatoproteasome is located at the synaptonemal complex and is essential for the assembly of its activator PA200. Accordingly, synapsis-deficient mice show delocalization of PSMA8 from the synaptonemal complex. Genetic analysis of Psma8-deficient mice shows normal meiotic DNA repair, crossing over formation and an increase of spermatocytes at metaphase I and metaphase II which either enter into apoptosis or slip to give rise to an early spermatid arrest and infertility. Thus, spermatoproteasome-dependent histone degradation is dispensable for meiotic recombination. We show that PSMA8 deficiency alters the proteostasis of several key meiotic players such as acetylated histones, SYCP3, SYCP1, CDK1 and TRIP13 which in turn leads to an aberrant meiotic exit and early spermatid arrest prior to the histone displacement process that take place subsequently.

cell biology↗