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Pathogen genomics has increasingly been integrated into infectious disease surveillance, outbreak detection, and response globally. However, formal evaluation of pathogen genomic surveillance systems has been a major gap. In Australia, the AusTrakka platform was established and deployed nationally to address barriers to genomic data sharing across jurisdictions, enhance interoperability and usability, and improve governance of public health genomic data. Here we present our evaluation of AusTrakka and examine how its utilisation and impact shifted throughout the COVID-19 pandemic. We utilised the US Centers for Disease Control (CDC) Updated Guidelines for Evaluating Public Health Surveillance Systems to guide assessment of the AusTrakka platform. The evaluation used a mixed-methods approach consisting of a quantitative analysis of AusTrakka utilisation data throughout the COVID-19 pandemic and a qualitative component comprised key informant interviews and analysis of investigation reports produced by the AusTrakka National Analysis Team. Quantitative and qualitative data were collected concurrently between June 2020 and October 2022. Semi-structured individual and group interviews were held with key informants (n = 63) representing all jurisdictions across Australia and New Zealand. These included individuals representing public health laboratories and health departments, infectious disease physicians, genomic epidemiologists, and bioinformaticians. AusTrakka users reported that the platform had a very high degree of usefulness as a centralised platform to enable sharing sequence data across jurisdictions, facilitate multijurisdictional outbreak investigations, and clarify transmission chains. Acceptability was a key system that contributed to the usefulness of the platform, enhanced through collective design of data governance frameworks. Integration of epidemiological data with the pathogen genomic data was an ongoing challenge in data completeness. Robust evaluation of pathogen genomics surveillance systems is critical to identify contextual and system elements that impact the capacity of these systems to accomplish their objectives. Our findings demonstrate the importance of strong stakeholder engagement in developing data governance mechanisms for pathogen genomics in ultimately ensuring the capacity of surveillance systems to detect outbreaks and support public health utility, and reinforce the value of a nationally developed, purpose-built approach in Australia.

The clinical phenotype and pathogenic mechanism of 46,XY disorders of sex development (DSD) are complex, and several pathogenic variants are identified by next-generation sequencing. However, these variants currently require additional interpretation and validation prior to their application in 46,XY DSD diagnosis and clinical guidance. Here, we identified three genetic variants in two 46,XY DSD patients by whole exome sequencing screening and Sanger sequencing validation. The pathogenicity of three genetic variants was identified by in silico analysis and functional experiments. One patient carrying the reported pathogenic variant (c.319 C > T) of NR5A1 showed a phenotype of 46,XY complete gonadal dysgenesis, which was different from the reported 46,XY partial gonadal dysgenesis. These findings suggested that the variant (c.319 C > T) of NR5A1 contributes to the clinical phenotypic heterogeneity of 46,XY DSD. The other patient carried two genetic variants, among which the c.1252 C > T variant of NR5A1 produced truncated protein and lost the transcriptional activation of NR5A1 to the targeted genes. The other c.769G > A variant of DHX37 had no significant effect on the expression level and cellular localization of DHX37, and the downstream signaling pathway of DHX37. Moreover, the in silico and structural analysis identified the c.769G > A variant of DHX37 as a deleterious variant that may affect DHX37 function. According to the American College of Medical Genetics and Genomics guidelines and relevant literature reports, combined with the patient's clinical phenotype and pedigreed analysis, it is proposed that the likely pathogenic variant identified in this patient is the c.1252 C > T variant of NR5A1. Nonetheless, the potential pathogenicity of the DHX37 (c.769G > A) variant of this patient also merits further investigation and consideration. Our results have expanded the clinical phenotype spectrum and genetic diagnosis spectrum of 46,XY DSD, which will contribute to the accurate diagnosis and treatment guidance for 46,XY DSD patients and provide evidence-based genetic counseling for 46,XY DSD family fertility.

Genomic medicine increasingly depends on patients' willingness to share genomic and medical data. While data sharing supports advances in personalised care, it also raises ethical and social concerns related to privacy, trust and participation. Understanding these factors requires attention to patients' health literacy and their capacity to interpret and act upon genomic information. A systematic review was conducted according to PRISMA guidelines to identify empirical studies published between 2015 and 2025 that explored patients' understanding of genomic information and their willingness to share data. Searches were performed in PubMed, Web of Science and Scopus. Eligible studies included qualitative, quantitative and mixed-methods designs. Findings were synthesised thematically and Nutbeam's model of health literacy was used in the discussion to interpret the results. Fifteen studies met the inclusion criteria. Participants demonstrated basic understanding of genetic terms but limited knowledge of data infrastructures and governance. Trust was a central factor influencing willingness to share data, often compensating for limited genomic literacy. Moral and altruistic motives encouraged engagement, whereas financial considerations played a minor, context-dependent role. Data sharing in genomic medicine relies on more than factual knowledge. Strengthening health literacy through transparent, dialogue-based, and participatory approaches can promote informed, autonomous, and ethically responsible participation in genomic research.

Hypervirulent Klebsiella pneumoniae (hvKp)-associated pyogenic liver abscess is most commonly linked to K1/K2 capsule serotypes and canonical lineages such as ST23, ST65, and ST86. Reports of hvKp outside these lineages remain rare but carry significant public health implications. We investigated an unusual case of liver abscess in an immunocompetent patient caused by hvKp sequence type 111 (ST111). Five isolates (KP1-KP5) recovered from a patient with pyogenic liver abscess were characterized by antimicrobial susceptibility testing, whole-genome sequencing, and pulsed-field gel electrophoresis. To investigate the contribution of the virulence plasmid to the host strain, CRISPR/Cas9-mediated plasmid curing was performed, followed by functional analyses including phenotypic characterization and a murine infection model. In addition, comparative genomic analyses were conducted to elucidate the epidemiological relationships and genetic determinants underlying hypervirulence. The five isolates recovered from the patient were genetically identical. Genomic analysis identified a 181 kb IncHI1B/IncFIB virulence plasmid encoding rmpADC and the salmochelin cluster (iroBCDN), but lacking iuc and rmpA2. Remarkably, the plasmid also carried the yersiniabactin locus (ybt), typically chromosomal in origin. Comparative genomics revealed that similar ST111 strains have been reported exclusively in China, suggesting clonal expansion of a previously unrecognized hvKp lineage. Functional assays demonstrated that plasmid curing abolished the hypermucoviscous phenotype, reduced capsule production, and completely attenuated virulence in murine models, confirming the plasmid as the principal driver of hypervirulence. Interestingly, plasmid loss enhanced biofilm formation and alleviated growth burden, indicating fitness trade-offs associated with virulence. This study describes a rare case of hvKp ST111 liver abscess and identifies a novel plasmid conferring hypervirulence. These findings broaden the recognized diversity of hvKp and highlight that non-canonical lineages can acquire potent virulence determinants capable of causing severe disease. Ongoing clinical and genomic surveillance is essential to detect and contain emerging hvKp clones before widespread dissemination.

Accessory genome regions of plant pathogenic fungi, which are highly variable and consist of niche-adaptive genes, play a crucial role in shaping host-specific interactions but are notoriously difficult to assemble. Fusarium oxysporum causes some of the world’s most economically devasting diseases, however, understanding how it interacts with its host is hindered by challenges in assembly of accessory genome regions/chromosomes, even with long read sequencing technologies. F. oxysporum f. sp. lactucae (FOLac) races 1 and 4 possess highly similar core genomes but cause distinct virulence phenotypes on specific lettuce cultivars. The availability of fully assembled genomes for the two races is needed to advance our understanding of the genetic basis of pathogenicity and the evolutionary processes underlying the diversification of FOLac and other F. oxysporum pathogens. We developed an assembly workflow for generating gapless, telomere-to-telomere (T2T) complete genome assemblies for FOLac races 1 and 4. The T2T assemblies allowed for the identification of 16 chromosomes (5 accessory) and 20,616 predicted genes for race 1 and 19 chromosomes (8 accessory) and 20,292 predicted genes for race 4. Comparative genomics revealed major structural differences in their accessory genome regions, including genome rearrangement and large-scale chromosome duplication, with results suggesting transposable elements as the main drivers of those genomic changes. The analysis of Secreted in Xylem (SIX) effector gene profiles uncovered a similar presence/absence pattern among FOLac races 2–4, distinguishing them from race 1. Searches for genes unique to each race resulted in the identification of 687 race 1- and 536 race 4-specific genes. Assembly and genomic features comparing T2T to contig-level Illumina assemblies showed that 17–23% of genome sizes and ~ 10% of predicted genes were missing from Illumina assembly, mostly within accessory genome regions. T2T assemblies revealed large-scale differences in accessory genome structure and content between two otherwise highly similar pathogenic races. These differences provide a framework for understanding evolutionary processes that led to the diversification of pathogens within F. oxysporum on a fine evolutionary timescale, the identification of genes that may be responsible for host-pathogen interaction, and the identification of race-specific sequences useful for diagnostics. The online version contains supplementary material available at 10.1186/s12864-026-12744-5.

Cognitive dysfunction ("brain fog") is a commonly reported post-COVID-19 symptom. Leveraging data from five general population cohorts across four European countries (Estonia, Iceland, Norway, and Sweden), we assessed long-term prevalence of impaired subjective cognitive function among individuals diagnosed with COVID-19 by acute illness severity. The included cohorts consisted of adult participants recruited from March 2020 and followed with self-report measures of cognitive function and past COVID-19 infection (except one cohort consisting of clinically confirmed COVID-19 cases) through February 2023. In a cross-sectional analysis we contrasted the prevalence of impaired cognitive function among individuals with and without a COVID-19 diagnosis, overall and by illness severity up to 32&#xa0;months post-diagnosis. We adjusted for age, gender, education, relationship status, binge drinking, body mass index, previous psychiatric diagnosis, number of chronic medical conditions, and response period. In a longitudinal analysis, we assessed potential changes in cognitive function scores before and after COVID-19 diagnosis. The study population consisted of 153,841 participants (71% women), with 31,359 (20.4%) reporting a positive COVID-19 test. Overall, a COVID-19 diagnosis was not statistically significantly associated with increased prevalence ratio (PR) of impaired cognitive function (PR 1.30 [95% CI: 0.98-1.71]). Individuals bedridden due to COVID-19 for 1-6&#xa0;days (PR 1.38 [95% CI 0.96-1.99]) or&#x2009;&#x2265;&#x2009;7&#xa0;days (2.59 [1.55-4.33]) had higher prevalence of impaired cognitive function compared to those never diagnosed, while individuals never bedridden had a lower prevalence to those never diagnosed with COVID-19 (0.89 [0.80-1.00]). These findings were corroborated in the longitudinal analysis where a pre- to post diagnosis decline in cognitive function was observed among individuals bedridden due to COVID-19 (p&#x2009;<&#x2009;0.0001). The data indicates that a severe COVID-19 acute illness course is associated with impaired cognitive function up to 18-32&#xa0;months after COVID-19 diagnosis.

Streptococcus periodonticum is a facultative anaerobic, Gram-positive coccus originally isolated from human periodontitis lesions and implicated in colorectal cancer pathogenesis. This study aimed to comprehensively characterize the genome of strain CRC221, isolated from human colorectal tumor tissue, to support future research on its potential role in tumorigenesis. Genomic DNA from strain CRC221 was sequenced using Illumina NovaSeq 6000 and PacBio platforms. The final assembly yielded a complete circular chromosome of 1,851,769&#xa0;bp with 38.81% GC content. Structural annotation predicted 1,837 genes, comprising 1,707 protein-coding sequences (CDSs), 12 rRNAs, 59 tRNAs, 3 non-coding RNAs, and 56 pseudogenes. Functional annotation associated most CDSs with core bacterial survival pathways, particularly carbohydrate and amino acid metabolism. Notably, 94 genes were annotated as virulence factors, 68 as antibiotic resistance genes, and 319 as pathogen-host interaction factors. Comparative genomics revealed an ANI of 97.51% and a dDDH value of 71.8% against the reference S. periodonticum genome (GCA_003963555.1). Pan-genome analysis indicated an open genome architecture containing 199 conserved core genes. These genomic data provide a foundation for investigating the biological characteristics of intratumoral S. periodonticum and its potential relevance to colorectal cancer.

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Understanding recombination rates is crucial in evolutionary biology, as recombination shapes genetic diversity, natural selection, and adaptation. We investigated recombination rate variation in Chironomus riparius across different latitudes, seasons, and experimental treatments using Pool-seq data from five studies and the ReLERNN neural network-based method. We examined its relationship with genetic diversity, GC content, and FST, assessing causality through structural equation modeling. In natural populations, recombination rates showed no clear latitudinal pattern, likely due to interactions between climate-driven selection, demographic history and regional environmental heterogeneity. However, seasonal variation was evident, with higher recombination rates in autumn than winter, possibly due to temperature-induced plasticity or seasonal bottlenecks. A cold snap in March 2018 triggered a sharp recombination increase, potentially suggesting a stress-induced adaptive response. Across datasets, recombination rates were correlated with genetic diversity and other genomic parameters, with structural equation models (SEMs) indicating that recombination and selection jointly shape patterns of &#x3c0; and differentiation, while relationships with GC content and TEs counts varied among environmental and experimental contexts. In experimental populations, thermal regimes alone had little effect on recombination; instead, adaptation to laboratory conditions and specific stressors drove recombination changes. Exposure to microplastics led to a genome-wide reduction in recombination, likely due to stress-induced DNA repair prioritizing genome integrity, whereas cadmium exposure generally suppressed recombination. Our results demonstrate that recombination in C. riparius is a highly dynamic trait influenced by environmental conditions, selection, and genomic context. By integrating ecological variation, experimental evolution, and multivariate genomic analyses, this study highlights recombination as a context-dependent process that responds to both natural and anthropogenic stressors and interacts with multiple features of genome architecture.

We investigated the role of copy number variations (CNVs) in Parkinson's disease (PD) using genotyping data from 10,815 patients (2731 early-onset PD, EOPD) and 8901 controls from the COURAGE-PD consortium. CNVs were analyzed using a sliding window genome-wide association and burden approach. No genome-wide significant CNVs were detected in the overall cohort, but a robust deletion spanning exons 2-6 of PRKN was identified in EOPD cases, validated by MLPA, and replicated in the GP2 dataset (23,089 cases, 18,824 controls). CNV burden was significantly enriched in PD-related genes, primarily driven by PRKN, with the strongest effect observed in EOPD. PRKN CNV carriers showed earlier age at onset, confirmed by survival analysis. No association was observed for genome-wide or large CNV burden. Our findings reinforce the pivotal role of PRKN deletions in early-onset PD and highlight the need for high-resolution CNV analysis in large cohorts to uncover additional rare contributors to PD risk.

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Chromatin insulators demarcate the genome into distinct transcriptional domains and contribute to higher-order genome organization. In Drosophila, Su(Hw), CP190, and Mod(mdg4)67.2 are core protein components of the gypsy insulator complex. Multimerization of these core components contributes to the formation of large structures within the nucleus termed insulator bodies. Post-translational modifications of insulator proteins appear to affect insulator body localization and to be required for full insulator activity, but few factors involved in these processes have been identified. To address this gap in understanding, we performed a high-throughput visual screen for Mod(mdg4)67.2-GFP localization using a ubiquitination-related RNAi library. We identified ubiquitination pathway proteins Effete (Eff) and Cullin 4 (Cul4), as novel regulators of CP190 localization and function. Both Eff and Cul4 physically associate with gypsy insulator proteins and promote gypsy-dependent insulator barrier activity. Moreover, Cul4 extensively colocalizes with CP190 on chromatin and assists in the recruitment of CP190 to gypsy sites. Both Eff and Cul4 affect transcription near topologically associating domain (TAD) borders, with Eff specifically altering the three-dimensional (3D) nuclear positioning of gypsy insulator sites. Our findings reveal a novel role for ubiquitination pathway-related enzymes in chromatin insulator activity, 3D genome organization, and gene expression.

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Mobilized colistin resistance (mcr) gene has emerged as a major driver of colistin resistance. Therefore, this study aimed to determine the distribution of mcr-variants and mcr-carrying genomes deposited in the NCBI database by sample collection periods and across continents, countries, genera, species, and ecosystems. In this database mining study, the keyword "mcr" was used to identify all mcr-carrying genomes deposited in the NCBI Pathogen Detection database until June 07, 2025, 12h15 GMT. A purely descriptive approach was used in this study, and percentages were calculated by dividing the number of an event by the total number of events (percentage&#x2009;=&#x2009;n/Nx100). Of the 2422739 whole genomes registered in the NCBI database, 18785 (0.78%) carried complete mcr variant sequences. Seventy-seven mcr subvariants were detected, including mostly mcr-1.1 (9431/18785; 50%), and mcr-9.1 (5971/18785; 32%). Mcr-9.1 was the most frequently detected subvariant in several genera, including Serratia spp. (17/17; 100%), Cronobacter spp. (155/160; 97%), and Pluralibacter spp. (19/20; 95%), whereas mcr-1.1 was the most commonly detected subvariant in Escherichia and Shigella spp. (8235/9678; 85%). Regarding geographical distribution, mcr-1.1 was the most observed subvariant in Asia (6759/9033; 75%) and Europe (1886/4680; 40%), whereas mcr-9.1 was the most identified in America (2982/4017; 74%) and Oceania (546/771; 71%). In Africa, mcr-10.1 (52/160; 33%), and mcr-1.1 (50/160; 31%) were the most frequent subvariants. Mcr-carrying genomes deposited in the NCBI database were distributed across ecosystems, including humans (n&#x2009;=&#x2009;8185), animals (n&#x2009;=&#x2009;4521), the environment (n&#x2009;=&#x2009;468), and food (n&#x2009;=&#x2009;48). The sample collection years for mcr-carrying bacteria ranged from 1953 to 2025, and the distribution of mcr-carrying genomes was as follows: 1953-1990 (n&#x2009;=&#x2009;49), 1991-1999 (n&#x2009;=&#x2009;47), 2000-2009 (n&#x2009;=&#x2009;704), 2010-2019 (n&#x2009;=&#x2009;12810), and 2020-2025 (n&#x2009;=&#x2009;4297). Another key finding was that 705 of the 18785 mcr-carrying genomes deposited in the NCBI database (3.8%) harbored multiple mcr genes, including 693 and 12 genomes co-carrying two and three mcr genes, respectively. Mcr-carrying bacteria represent a significant One Health concern because of their major role in colistin resistance and potential for global dissemination. Key actions, such as global surveillance, One Health monitoring, and appropriate stewardship, should be taken to preserve the efficacy of colistin for decades.