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One of the main goals of human genetics is to understand the connections between genomic variation and the predisposition to develop a complex disorder. These disease–variant associations are usually studied in a single independent manner, disregarding the possible effect derived from the interaction between genomic variants. In particular, in a background of complex diseases, these interactions can be directly linked to the disorder and may play an important role in disease development. Although their study has been suggested to help complete the understanding of the genetic bases of complex diseases, this still represents a big challenge due to large computing demands. Here, we take advantage of high-performance computing technologies to tackle this problem by using a combination of machine learning methods and statistical approaches. As a result, we created a containerized framework that uses multifactor dimensionality reduction (MDR) to detect pairs of variants associated with type 2 diabetes (T2D). This methodology was tested on the Northwestern University NUgene project cohort using a dataset of 1,883,192 variant pairs with a certain degree of association with T2D. Out of the pairs studied, we identified 104 significant pairs: two of which exhibit a potential functional relationship with T2D. These results place the proposed MDR method as a valid, efficient, and portable solution to study variant interaction in real reduced genomic datasets., This work was partially financed by the European Commission (EU-HORIZON NEARDATA GA.101092644) and by the Universitat Politècnica de Catalunya (45-FPIUPC2018); it was also partially financed by Generalitat de Catalunya (AGAUR) under grant agreement 2021-SGR-00478; it was also partially financed by the Spanish Ministry of Science (MICINN), the Research State Agency (AEI), and European Regional Development Funds (ERDF/FEDER) under grant agreement PID2021-126248OB-I00, MCIN/AEI/10.13039/501100011033/FEDER, UE., Peer Reviewed, Postprint (published version)

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient., This work was supported by the Wellcome Trust (grant number WT QQ2016-2021, reference 206194, to S.B., S.L. and S.D.B.); the Bill & Melinda Gates Foundation (under Investment ID INV-003570 to S.A.M., A.v.G., M.d.P., S.D. and S.N.); the NIH (grant number R01AI160780 to H.S.); and the European Research Council (grant number 804744 to H.S. and N.L.). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We would like to thank all Global Pneumococcal Sequencing project partners; and M. O’Driscoll, S. Farr, and V. Carr for code review., Peer Reviewed, "Article signat per xx autors/es: Sophie Belman, Noémie Lefrancq, Susan Nzenze, Sarah Downs, Mignon du Plessis, Stephanie W. Lo, The Global Pneumococcal Sequencing Consortium, Lesley McGee, Shabir A. Madhi, Anne von Gottberg, Stephen D. Bentley & Henrik Salje", Postprint (published version)

Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. Streptococcus pneumoniae (the pneumococcus) is a respiratory bacterium responsible for a large proportion of infectious disease morbidity and mortality globally. Even in the post-vaccination era, the rates of invasive pneumococcal disease (IPD) remain stable in most countries, including Israel. To understand the geographical spread of the pneumococcus in Israel, we analysed 1174 pneumococcal genomes from patients with IPD across multiple regions. We included the evolutionary distance between pairs of isolates inferred using whole-genome data within a relative risk (RR) ratio framework to capture the geographical structure of S. pneumoniae. While we could not find geographical structure at the overall lineage level, the extra granularity provided by whole-genome sequence data showed that it takes approximately 5 years for invasive pneumococcal isolates to become fully mixed across the country., This study was co-funded by the Bill and Melinda Gates Foundation (grant codes OPP1034556 and OPP1189062) and the Wellcome Sanger Institute (core Wellcome grants 206194), Peer Reviewed, Postprint (published version)

Understanding how microbial pathogens adapt to treatments, humans and clinical environments is key to infer mechanisms of virulence, transmission and drug resistance. This may help improve therapies and diagnostics for infections with a poor prognosis, such as those caused by fungal pathogens, including Candida. Here we analysed genomic variants across approximately 2,000 isolates from six Candida species (C. glabrata, C. auris, C. albicans, C. tropicalis, C. parapsilosis and C. orthopsilosis) and identified genes under recent selection, suggesting a highly complex clinical adaptation. These involve species-specific and convergently affected adaptive mechanisms, such as adhesion. Using convergence-based genome-wide association studies we identified known drivers of drug resistance alongside potentially novel players. Finally, our analyses reveal an important role of structural variants and suggest an unexpected involvement of (para)sexual recombination in the spread of resistance. Our results provide insights on how opportunistic pathogens adapt to human-related environments and unearth candidate genes that deserve future attention., The T.G. group acknowledges support from the Spanish Ministry of Science and Innovation (grant numbers PID2021-126067NB-I00, CPP2021-008552, PCI2022-135066-2 and PDC2022-133266-I00), cofounded by ERDF ‘A way of making Europe’, as well as support from the Catalan Research Agency (grant number SGR01551), European Union’s Horizon 2020 research and innovation programme (grant number ERC-2016-724173), Gordon and Betty Moore Foundation (grant number GBMF9742), ‘La Caixa’ Foundation (grant number LCF/PR/HR21/00737) and Instituto de Salud Carlos III (IMPACT grant number IMP/00019 and CIBERINFEC CB21/13/00061-ISCIII-SGEFI/ERDF). M.A.S.-T. received a Predoctoral Fellowship from the ‘La Caixa’ Foundation (grant number LCF/BQ/DR19/11740023). The authors thank all of the members of the Gabaldón group for key support during this work. In particular H. Hovhannisyan, V. d. Olmo, D. Fuentes, M. Schiavinato, M. Marcet-Houben, G. Torruella, J. C. Núñez, U. Chorostecki and E. Księżopolska, who provided useful feedback, which was key for the project development. In addition, we thank M. Lleal for useful feedback in designing the figures., Peer Reviewed, Postprint (published version)

The incidence of Candida infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise epidemiological data on species and antimicrobial resistance incidence, but many countries lack appropriate surveillance programs. This study aims to bridge this gap for Morocco by identifying and phenotyping a year-long collection of clinical isolates (n = 93) from four clinics in Tetouan. We compared the current standard in species identification with molecular methods and assessed susceptibility to fluconazole and anidulafungin. Our results identified limitations in currently used diagnostics approaches, and revealed that C. albicans ranks as the most prevalent species with 60 strains (64.52%), followed by C. glabrata with 14 (15.05%), C. parapsilosis with 6 (6.45%), and C. tropicalis with 4 (4.30%). In addition, we report the first identification of C. metapsilosis in Morocco. Susceptibility results for fluconazole revealed that some isolates were approaching MICs resistance breakpoints in C. albicans (2), and C. glabrata (1). Our study also identified anidulafungin resistant strains in C. albicans (1), C. tropicalis (1), and C. krusei (2), rendering the two strains from the latter species multidrug-resistant due to their innate resistance to fluconazole. These results raise concerns about species identification and antifungal resistance in Morocco and highlight the urgent need for more accurate methods and preventive strategies to combat fungal infections in the country., T.G. group acknowledges support from the Spanish Ministry of Science and Innovation for grants PID2021-126067NB-I00, CPP2021-008552, PCI2022-135066-2, and PDC2022-133266-I00, cofounded by ERDF “A way of making Europe”; from the Catalan Research Agency (AGAUR) SGR01551; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742); from the “La Caixa” foundation (Grant LCF/PR/HR21/00737), and from the Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061-ISCIII-SGEFI/ERDF). I.A. is supported by Research Excellence PhD Fellowship (1UAE2020) from the National Center for Scientific and Technical Research (CNRST), as well as the opportunity granted through the Erasmus+ KA107 mobility program. J.C.N.-R. is funded by the Spanish Ministry of Science and Innovation from the project PGC2018-099921-B-I00 (grant number PRE2019-088193)., Peer Reviewed, Postprint (author's final draft)

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5’ (n=9) and 3’ (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5’ breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3’ breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively., This study was supported by the “la Caixa" Foundation (CLLEvolution - LCF/PR/HR17/52150017 [HR17-00221LCF] and CLLSYSTEMS - LCF/PR/HR22/52420015 [HR22-00172] Health Research 2017 and 2022 Programs, to EC), the European Research Council (to EC and JIM-S) under the European Union’s Horizon 2020 research and innovation program (810287, BCLLatlas, to EC), Ministry of Science and Innovation (MCIN) /AEI/10.13039/501100011033/ and European Regional Development Fund “Una manera de hacer Europa” (PID2021-123054OB-I00 to EC) and the Generalitat de Catalunya Suport Grups de Recerca AGAUR (2021-SGR01172 to EC and 2021-SGR-01293 to SB). HP-A is a recipient of a pre-doctoral fellowship from the Spanish Ministry of Science, Innovation and Universities (FPU19/03110). MD-F acknowledges the research support from the AECC Scientific Foundation. FN acknowledges research support from the American Association for Cancer Research (2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research, 21-40-11-NADE), European Hematology Association (EHA Junior Research Grant 2021, RG-202012-00245), and Lady Tata Memorial Trust (International Award for Research in Leukemia 2021-2022, LADY_TATA_21_3223). EC is an Academia Researcher of the “Institució Catalana de Recerca i Estudis Avançats” (ICREA) of the Generalitat de Catalunya., Peer Reviewed, "Article signat per 45 autors/es: Anna Carbó-Meix, Francesca Guijarro, Luojun Wang, Marta Grau, Romina Royo, Gerard Frigola, Heribert Playa-Albinyana, Marco M. Bühler, Guillem Clot, Martí DuranFerrer, Junyan Lu, Isabel Granada, Maria-Joao Baptista, José-Tomás Navarro, Blanca Espinet, Anna Puiggros, Gustavo Tapia, Laura Bandiera, Gabriella De Canal, Emanuela Bonoldi, Fina Climent, Inmaculada Ribera-Cortada, Mariana Fernández-Caballero, Esmeralda de la Banda, Janilson do Nascimento, Alberto Pineda, Dolors Vela, María Rozman, Marta Aymerich, Charlotte Syrykh, Pierre Brousset, Miguel Perera, Lucrecia Yáñez, Jesús Xavier Ortin, Esperanza Tuset, Thorsten Zenz, James R. Cook, Steven H. Swerdlow, José I. Martín-Subero, Dolors Colomer, Estella Matutes, Sílvia Beà, Dolors Costa,Ferran Nadeu and Elías Campo", Postprint (published version)

Summary Real-world data have revealed that a substantial portion of patients with myelodysplastic syndromes (MDS) does not respond to epigenetic therapy with hypomethylating agents (HMAs). The cellular and molecular reasons for this resistance to the demethylating agent and biomarkers that would be able to predict the treatment refractoriness are largely unknown. In this study, we shed light on this enigma by characterizing the epigenomic profiles of patients with MDS treated with azacitidine. Our approach provides a comprehensive view of the evolving DNA methylation architecture of the disease and holds great potential for advancing our understanding of MDS treatment responses to HMAs., We thank CERCA Programme/Generalitat de Catalunya for institutional support. The research leading to these results has received funding from MCIN/AEI/10.13039/501100011033/ and the European Regional Development Fund, ‘A way to make Europe’ ERDF (project PID2021-125282OB-I00); Departament de Recerca i Universitats/Generalitat de Catalunya (2021 SGR 01494) and the Cellex Foundation (CEL007). Ignacio Campillo-Marcos is funded by a Juan de la Cierva-Formación fellowship from the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 NextGenerationEU/PRTR (FJC2020-044658-I)., Peer Reviewed, "Article signat per 20 autors/es: Aleix Noguera-Castells, Ignacio Campillo-Marcos, Veronica Davalos, Carlos A. García-Prieto, David Valcárcel, Antonieta Molero, Laura Palomo, Norbert Gattermann, Michael Wulfert, Lorea Chaparro-González, Francesc Solé, Marta Cabezón, María J. Jiménez-Lorenzo, Blanca Xicoy, Lurdes Zamora, Alessia De Stefano, Irene Casalin, Carlo Finelli, Matilde Y. Follo, Manel Esteller", Postprint (published version)

Hybridisation is the crossing of two divergent lineages that give rise to offspring carrying an admixture of both parental genomes. Genome sequencing has revealed that this process is common in the Saccharomycotina, where a growing number of hybrid strains or species, including many pathogenic ones, have been recently described. Hybrids can display unique traits that may drive adaptation to new niches, and some pathogenic hybrids have been shown to have higher prevalence over their parents in human and environmental niches, suggesting a higher fitness and potential to colonise humans. Here, we discuss how hybridisation and its genomic and phenotypic outcomes can shape the evolution of fungal species and may play a role in the emergence of new pathogens., The authors acknowledge support from the Spanish Ministry of Science and Innovation (Grant numbers PID2021-126067NB-I00, CPP2021-008552, PCI2022-135066-2 and PDC2022-133266-I00), cofounded by ERDF 'A way of making Europe', as well as support from the Catalan Research Agency (AGAUR) (Grant number SGR01551), European Union’s Horizon 2020 research and innovation programme (Grant number ERC-2016-724173), Gordon and Betty Moore Foundation (Grant number GBMF9742), 'La Caixa' foundation (Grant number LCF/PR/HR21/00737) and Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061-ISCIII-SGEFI/ERDF)., Peer Reviewed, Postprint (published version)

Muscular dystrophies (MDs) are inherited genetic diseases causing weakness and degeneration of muscles. The distribution of muscle weakness differs between MDs, involving distal muscles or proximal muscles. While the mutations in most of the MD-associated genes lead to either distal or proximal onset, there are also genes whose mutations can cause both types of onsets. We hypothesized that the genes associated with different MD onsets code proteins with distinct cellular functions. To investigate this, we collected the MD-associated genes and assigned them to three onset groups: genes mutated only in distal onset dystrophies, genes mutated only in proximal onset dystrophies, and genes mutated in both types of onsets. We then systematically evaluated the cellular functions of these gene sets with computational strategies based on functional enrichment analysis and biological network analysis. Our analyses demonstrate that genes mutated in either distal or proximal onset MDs code proteins linked with two distinct sets of cellular processes. Interestingly, these two sets of cellular processes are relevant for the genes that are associated with both onsets. Moreover, the genes associated with both onsets display high centrality and connectivity in the network of muscular dystrophy genes. Our findings support the hypothesis that the proteins associated with distal or proximal onsets have distinct functional characteristics, whereas the proteins associated with both onsets are multifunctional., This work is supported by the funding from the European Union’s Horizon 2020 research and innovation programme under the EJP RD COFUND-EJP N° 825575., Peer Reviewed, Postprint (published version)

The Catalan Initiative for the Earth BioGenome Project (CBP) is an EBP-affiliated project network aimed at sequencing the genome of the > 40000 eukaryotic species estimated to live in the Catalan-speaking territories (Catalan Linguistic Area, CLA). These territories represent a biodiversity hotspot. While covering less than 1% of Europe, they are home to about one fourth of all known European eukaryotic species. These include a high proportion of endemisms, many of which are threatened. This trend is likely to get worse as the effects of global change are expected to be particularly severe across the Mediterranean Basin, particularly in freshwater ecosystems and mountain areas. Following the EBP model, the CBP is a networked organization that has been able to engage many scientific and non-scientific partners. In the pilot phase, the genomes of 52 species are being sequenced. As a case study in biodiversity conservation, we highlight the genome of the Balearic shearwater Puffinus mauretanicus, sequenced under the CBP umbrella.

Human-mediated habitat destruction has had a profound impact on increased species extinction rates and population declines worldwide. The coastal development in the United Arab Emirates (UAE) over the last two decades, serves as an example of how habitat transformation can alter the landscape of a country in just a few years. Here, we study the genomic implications of habitat transformation in the Critically Endangered Emirati Leaf-toed Gecko (Asaccus caudivolvulus), the only endemic vertebrate of the UAE. We generate a high-quality reference genome for this gecko, representing the first refer ence genome for the family Phyllodactylidae, and produce whole-genome resequencing data for 23 specimens from 10 different species of leaf-toed geckos. Our results show that A. caudivolvulus has consistently lower genetic diversity than any other Arabian species of Asaccus, suggesting a history of ancient population declines. However, high levels of recent inbreeding are recorded among populations in heavily developed areas, with a more than 50% increase in long runs of homozygosity within a 9-year period. Moreover, results suggest that this species does not effectively purge deleterious mutations, hence making it more vulnerable to future stochastic threats. Overall, results show that A. caudivolvulus is in urgent need of protection, and habitat preservation must be warranted to ensure the species' survival.

Producción Científica, Circadian rhythms integrate a finely tuned network of biological processes recurring every 24 h, intricately coordinating the machinery of all cells. This self-regulating system plays a pivotal role in synchronizing physiological and behavioral responses, ensuring an adaptive metabolism within the environmental milieu, including dietary and physical activity habits. The systemic integration of circadian homeostasis involves a balance of biological rhythms, each synchronically linked to the central circadian clock. Central to this orchestration is the temporal dimension of nutrient and food intake, an aspect closely interwoven with the neuroendocrine circuit, gut physiology, and resident microbiota. Indeed, the timing of meals exerts a profound influence on cell cycle regulation through genomic and epigenetic processes, particularly those involving gene expression, DNA methylation and repair, and non-coding RNA activity. These (epi)genomic interactions involve a dynamic interface between circadian rhythms, nutrition, and the gut microbiota, shaping the metabolic and immune landscape of the host. This research endeavors to illustrate the intricate (epi)genetic interplay that modulates the synchronization of circadian rhythms, nutritional signaling, and the gut microbiota, unravelling the repercussions on metabolic health while suggesting the potential benefits of feed circadian realignment as a non-invasive therapeutic strategy for systemic metabolic modulation via gut microbiota. This exploration delves into the interconnections that underscore the significance of temporal eating patterns, offering insights regarding circadian rhythms, gut microbiota, and chrono-nutrition interactions with (epi)genomic phenomena, thereby influencing diverse aspects of metabolic, well-being, and quality of life outcomes., Instituto Carlos III, Contratos Sara Borrell - (grant CD22/00011), Comunidad Autónoma de Madrid, Consejería de Educación, CIBERobn, Instituto IMDEA Alimentación - (project METAINFLAMACION: Y2020/BIO-6600)

Understanding the intricate roles of RNA molecules in virulence and host-pathogen interactions can provide valuable insights into combatting infections and improving human health. Although much progress has been achieved in understanding transcriptional regulation during host-pathogen interactions in diverse species, more is needed to know about the structure of pathogen RNAs. This is particularly true for fungal pathogens, including pathogenic yeasts of the Candida genus, which are the leading cause of hospital-acquired fungal infections. Our work addresses the gap between RNA structure and their biology by employing genome-wide structure probing to comprehensively explore the structural landscape of mRNAs and long non-coding RNAs (lncRNAs) in the four major Candida pathogens. Specifically focusing on mRNA, we observe a robust correlation between sequence conservation and structural characteristics in orthologous transcripts, significantly when sequence identity exceeds 50%, highlighting structural feature conservation among closely related species. We investigate the impact of single nucleotide polymorphisms (SNPs) on mRNA secondary structure. SNPs within 5′ untranslated regions (UTRs) tend to occur in less structured positions, suggesting structural constraints influencing transcript regulation. Furthermore, we compare the structural properties of coding regions and UTRs, noting that coding regions are generally more structured than UTRs, consistent with similar trends in other species. Additionally, we provide the first experimental characterization of lncRNA structures in Candida species. Most lncRNAs form independent subdomains, similar to human lncRNAs. Notably, we identify hairpin-like structures in lncRNAs, a feature known to be functionally significant. Comparing hairpin prevalence between lncRNAs and protein-coding genes, we find enrichment in lncRNAs across Candida species, humans, and Arabidopsis thaliana, suggesting a conserved role for these structure, The author(s) declare financial support was received for the research, authorship, and/or publication of this article. TG group acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by the European Regional Development Fund (ERDF); from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742); from the “La Caixa” foundation (Grant LCF/PR/HR21/00737), and the Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061 – ISCIII-SGEFI/ERDF). UC was partly funded through MICINN (IJC2019-039402-I) and MICINN (RYC2021-032641-I)., Peer Reviewed, Postprint (published version)

The absence of robust interspecific isolation barriers among pantherines, including the iconic South American jaguar (Panthera onca), led us to study molecular evolution of typically rapidly evolving reproductive proteins within this subfamily and related groups. In this study, we delved into the evolutionary forces acting on the zona pellucida (ZP) gamete interaction protein family and the sperm-oocyte fusion protein pair IZUMO1-JUNO across the Carnivora order, distinguishing between Caniformia and Feliformia suborders and anticipating few significant diversifying changes in the Pantherinae subfamily. A chromosome-resolved jaguar genome assembly facilitated coding sequences, enabling the reconstruction of protein evolutionary histories. Examining sequence variability across more than 30 Carnivora species revealed that Feliformia exhibited significantly lower diversity compared to its sister taxa, Caniformia. Molecular evolution analyses of ZP2 and ZP3, subunits directly involved in sperm-recognition, unveiled diversifying positive selection in Feliformia, Caniformia and Pantherinae, although no significant changes were linked to sperm binding. Structural cross-linking ZP subunits, ZP4 and ZP1 exhibited lower levels or complete absence of positive selection. Notably, the fusion protein IZUMO1 displayed prominent positive selection signatures and sites in basal lineages of both Caniformia and Feliformia, extending along the Caniformia subtree but absent in Pantherinae. Conversely, JUNO did not exhibit any positive selection signatures across tested lineages and clades. Eight Caniformia-specific positive selected sites in IZUMO1 were detected within two JUNO-interaction clusters. Our findings provide for the first time insights into the evolutionary trajectories of ZP proteins and the IZUMO1-JUNO gamete interaction pair within the Carnivora order., FP received the Wood-Wheelan Research Fellowship from International Union of Biochemistry and Molecular Biology (IUBMB) and travel fellowship from CONICET partial funding program for short stays abroad for postdoctoral fellows. PS and FP are CONICET researchers. PS is a senior researcher of PIP 2015 and PICT 2015 grants, Peer Reviewed, Postprint (author's final draft)

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants.Materials and methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility ()Db between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants.Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated Db between variants, revealing that: (i) Db increased progressively from the Alpha to the Omicron variant; (ii) Db showed a high degree of variability within Omicron variants; (iii) a higher Db was associated with a later emergence of the variant within a country; (iv) a higher degree of immunization of the population against previous variants was associated with a higher Db for the Delta variant; (v) larger countries exhibited smaller Db, suggesting regionally diverse outbreaks within the same country; and finally (vi) the model reliably captures the dynamics of competing variants, even in complex scenarios.Conclusion: The use of mathematical models allows for precise and reliable estimation of daily cases of each variant. By quantifying Db, we have tracked the OPEN ACCESSEDITED BYTamer Oraby, The University of Texas Rio Grande Valley, United StatesREVIEWED BYFulvia Pimpinelli, San Gallicano Dermatological Institute IRCCS, ItalyMd Rafiul Islam, University of the Incarnate Word, United States*CORRESPONDENCEClara Prats clara.prat, The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The research leading to these results received funding from Ayudas Fundación BBVA a proyectos investigación científica 2021 under the project BBVA: Epidemiological modeling of SARS-CoV-2 in a post-pandemic surveillance context: an open platform for mid-term scenarios and short-term predictions, and from grants 2021 SGR 00582 funded by Agència de Gestió d’Ajuts Universitaris i de Recerca, and PID-2022- 139216NB-I00 funded by Ministerio de Ciencia e Innovación (MCIN/ AEI/10.13039/501100011033) and by ‘ERDF: A way of making Europe’, by the European Union., Postprint (published version)

Arm usage has substantially grown in the High-Performance Computing (HPC) community. Japanese supercomputer Fugaku, powered by Arm-based A64FX processors, held the top position on the Top500 list between June 2020 and June 2022, currently sitting in the fourth position. The recently released 7th generation of Amazon EC2 instances for compute-intensive workloads (C7 g) is also powered by Arm Graviton3 processors. Projects like European Mont-Blanc and U.S. DOE/NNSA Astra are further examples of Arm irruption in HPC. In parallel, over the last decade, the rapid improvement of genomic sequencing technologies and the exponential growth of sequencing data has placed a significant bottleneck on the computational side. While most genomics applications have been thoroughly tested and optimized for x86 systems, just a few are prepared to perform efficiently on Arm machines. Moreover, these applications do not exploit the newly introduced Scalable Vector Extensions (SVE). This paper presents GenArchBench, the first genome analysis benchmark suite targeting Arm architectures. We have selected computationally demanding kernels from the most widely used tools in genome data analysis and ported them to Arm-based A64FX and Graviton3 processors. Overall, the GenArch benchmark suite comprises 13 multi-core kernels from critical stages of widely-used genome analysis pipelines, including base-calling, read mapping, variant calling, and genome assembly. Our benchmark suite includes different input data sets per kernel (small and large), each with a corresponding regression test to verify the correctness of each execution automatically. Moreover, the porting features the usage of the novel Arm SVE instructions, algorithmic and code optimizations, and the exploitation of Arm-optimized libraries. We present the optimizations implemented in each kernel and a detailed performance evaluation and comparison of their performance on four different HPC machines (i.e., A64FX, Graviton3, Intel Xeon, This work has been partially supported by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 (contracts PID2019-107255GB-C21, PID2019-105660RB-C21, PID2022136454NB-C22, and TED2021-132634A-I00), by the Generalitat de Catalunya, Spain (contract 2021-SGR-763), by the Gobierno de Aragón (T58_23R research group), by the European Union NextGenerationEU/ PRTR, and by Lenovo BSC Contract-Framework Contract (2020)., Peer Reviewed, Postprint (published version)

Summary Background Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Methods Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994–2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008–2020) and historical isolates (1989–1993) were analysed by WGS (Illumina and/or MinION). Findings From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994–2001) and late-PCV13 (2016–2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0–45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5–32.0) (p = 0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0–86.0) to 85.7% (95.0% CI, 71.0–94.0) (p = 0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Interpretation Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population char, This study has been funded by Instituto de Salud Carlos III (ISCIII) “PI18/00339”, “PI21/01000”, “INT22/00096”, “FI22/00279”, CIBER “CIBERES-CB06/06/0037”, “CIBERINFEC-CB21/13/00009” and MSD grant “IISP 60168”., "Article signat per 21 autors/es: Sara Calvo-Silveria, Aida González-Díaz,Inmaculada Grau, José María Marimón, Emilia Cercenado, M DoloresQuesada, Antonio Casabella, Nieves Larrosa, José Yuste,Dàmaris Berbel, Marta Alonso, Fe Tubau, Sophie Belman, Irene Cadenas-Jiménez, Antonio J. Martín-Galiano, M Ángeles Domínguez, Sara Martí, Josefina Liñares, Román Pallarés, Jordi Càmara, and Carmen Ardanuy", Postprint (published version)

Motivation The interpretation of genomic data is crucial to understand the molecular mechanisms of biological processes. Protein structures play a vital role in facilitating this interpretation by providing functional context to genetic coding variants. However, mapping genes to proteins is a tedious and error-prone task due to inconsistencies in data formats. Over the past two decades, numerous tools and databases have been developed to automatically map annotated positions and variants to protein structures. However, most of these tools are web-based and not well-suited for large-scale genomic data analysis. Results To address this issue, we introduce 3Dmapper, a stand-alone command-line tool developed in Python and R. It systematically maps annotated protein positions and variants to protein structures, providing a solution that is both efficient and reliable., E.P-P and V.R-S are supported by the La Caixa Junior Leader Fellowship LCF/BQ/PI18/11630003. E.P-P also received support from the Spanish Ministry of Science [grant numbers RYC2019-026415-I and PID2019-107043RA-I00]. A.V. is supported by Institució Catalana de Recerca Avançada (ICREA). S.M. received support from the Asociación Española Contra el Cáncer (AECC) project LABAE20038PORT. This research has been conducted using the UK Biobank Resource under Application Number 54343. The results published here are in part based upon data generated by the TCGA Research Network (https://www.cancer.gov/tcga)., Peer Reviewed, Postprint (published version)