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Biology subjects

Luu, P.-L.

Publications and source records attributed to Luu, P.-L..

4 recordsLinked to original sources

A Draft Male Genome Assembly of the Slipper Lobster (Thenus australiensis) Reveals an XY System and a Validated Diagnostic Marker for Monosex Aquaculture.

The slipper lobster (Thenus australiensis) is rapidly emerging as a high-potential species for commercial aquaculture. Because females exhibit superior growth characteristics due to less frequent moulting after sexual maturity, developing monosex breeding strategies is highly desirable for industry profitability. However, the lack of genomic resources and early sex-identification tools has hindered this development. Here, we report the first draft male genome assembly for T. australiensis, generated using a combination of whole-genome shotgun sequencing, DArT-seq, and multi-tissue transcriptomics. The curated assembly spans 0.913 Gbp with high functional completeness (93.0% BUSCO), providing a robust repertoire of 30,100 protein-coding genes. Through k-mer subtraction and population-level DArT-seq genotyping, we provide definitive evidence that T. australiensis utilizes an XX/XY sex-determination system. Crucially, by identifying male-specific structural variations within a neo-Y locus, we developed a diagnostic PCR assay targeting a male-exclusive sequence. This 171 bp marker achieved 100% accuracy in phenotypic sex identification across wild-caught populations. Ultimately, these foundational genomic resources, combined with a highly reliable molecular sexing tool, provide the critical framework necessary for early sex sorting, broodstock management, and the commercial advancement of monosex slipper lobster farming. HighlightsO_LIFirst draft genome of slipper lobster (0.913 Gbp) assembled. C_LIO_LIMulti-omics approach confirms an XX/XY sex-determination system. C_LIO_LIDeveloped a 171 bp diagnostic PCR sex marker with 100% accuracy. C_LIO_LIFacilitates early sex sorting for profitable monosex aquaculture. C_LI

genomics↗

Candida auris can acquire antifungal resistance without selection pressure

The human fungal pathogen Candidozyma auris (formerly Candida auris) can cause prolonged infection outbreaks with high mortality rates in healthcare settings. Treatment failures of patients arise not only from antifungal drug resistance, but also from intra-species variability in pathogenicity as well as induced hypermutation events in response to clinical therapy. Whole genome sequencing was used to identify genetic mutations using the CDC mycoSNPs pipeline. Antifungal susceptibility testing was performed based on Clinical and Laboratory Standards Institute (CLSI) methods. We report here that the interlaboratory exchange of C. auris clinical isolates dried on sterile filter paper, resulted in the emergence of at least three distinct morphotypes following reconstitution. These distinct morphotypes exhibited differences in drug resistance and morphogenesis, linked to the accumulation of mutations in genes associated with azole and echinocandin resistance. Using whole genome sequencing, we identified several variants in TAC1B, MRR1 and FKS2 that correlate with altered drug susceptibilities. Experiments recapitulating filter paper shipment conditions revealed genetic and epigenetic changes, explaining the morphogenetic switching and altered azole resistance. Our findings demonstrate that C. auris can acquire mutations affecting drug resistance traits even in the absence of antifungal exposure, raising concerns about shipment preparation procedures across mycology laboratories. The results are of broad relevance for the medical mycology community, as they call for standardized protocols for exchanging clinical strains, but also experiments to verify phenotypic traits between laboratories. ImportancePathogenesis and antifungal drug resistance traits of Candida auris vary widely across clinical strains and are often attributed to elevated mutation rates. In fungal pathogen research, clinical strains are commonly exchanged between laboratories by transfer on filter paper, a convenient and widely used practice. However, in the case of a C. auris clinical strain received from a collaborating laboratory, we identified multiple acquired mutations. These genetic alterations caused marked changes in morphogenesis and antifungal susceptibility, demonstrating that resistance in C. auris can arise without antifungal selection pressure. Our findings highlight the potential for genetic and phenotypic diversification during routine strain handling and underscore the need for standardized protocols for exchanging clinical C. auris strains across mycology laboratories.

microbiology↗

BRG1 promotes transcriptional patterns that are permissive to proliferation in cancer cells

BackgroundBRG1 (encoded by SMARCA4) is a catalytic component of the SWI/SNF chromatin remodelling complex, with key roles in modulating DNA accessibility. Dysregulation of BRG1 is observed, but functionally uncharacterised, in a wide range of malignancies. We have probed the functions of BRG1 on a background of prostate cancer to investigate how BRG1 controls gene expression programs and cancer cell behaviour. ResultsOur investigation of SMARCA4 revealed that BRG1 is universally overexpressed in 486 tumours from The Cancer Genome Atlas prostate cohort, as well as in a complementary panel of 21 prostate cell lines. Next, we utilised a temporal model of BRG1 depletion to investigate the molecular effects on global transcription programs. Unexpectedly, depleting BRG1 had no impact on alternative splicing and conferred only modest effect on global expression. However, of the transcriptional changes that occurred, most manifested as down-regulated expression. Deeper examination found the common thread linking down-regulated genes was involvement in proliferation, including several known to increase prostate cancer proliferation (KLK2, PCAT1 and VAV3). Interestingly, the promoters of genes driving proliferation were bound by BRG1 as well as the oncogenic transcription factors, AR and FOXA1. We also noted that BRG1 depletion repressed genes involved in cell cycle progression and DNA replication but intriguingly, these pathways operated independently of AR and FOXA1. In agreement with transcriptional changes, depleting BRG1 conferred G1 arrest. ConclusionsOur data have revealed that BRG1 has capacity to drive oncogenesis by coordinating oncogenic pathways dependent on BRG1 for proliferation, cell cycle progression and DNA replication.

molecular biology↗

MethPanel: a parallel pipeline and interactive analysis tool for multiplex bisulphite PCR sequencing to assess DNA methylation biomarker panels for disease detection

BackgroundMultiplex bisulphite PCR sequencing is a convenient and scalable method to comprehensively profile DNA methylation at selected loci. The method is useful for validation of methylation biomarker panels on large clinical cohorts, as it can be applied to DNA isolated from fresh tissue, archival formalin fixed paraffin embedded tissue (FFPET) or circulating cell free DNA in plasma. However, successful clinical implementation of DNA methylation biomarkers for disease detection using multiplex bisulphite PCR sequencing, requires user-friendly sample analysis methods and a diversity of visualisation options, which are not met by current tools. ResultsWe have developed a computational pipeline with an interactive graphical interface, called MethPanel, in order to rapidly analyse multiplex bisulphite PCR sequencing data. MethPanel comprises a complete analysis workflow from genomic alignment to DNA methylation calling and supports an unlimited number of PCR amplicons and input samples. Moreover, MethPanel offers important and unique features, such as calculation of a polymorphism score and bisulphite PCR bias correction capabilities. MethPanel is designed so that the methylation data from all samples can be run in parallel on either a personal computer or a high performance computer. The outputs are also automatically forwarded to a shinyApp for convenient display, visualisation and sharing data with collaborators and clinicians. Importantly the data is centralised in one location, which aids storage management. Availability and ImplementationMethPanel is freely available at https://github.com/thinhong/MethPanel ConclusionMethPanel provides a novel parallel pipeline and interactive analysis tool for multiplex bisulphite PCR sequencing to assess DNA methylation marker panels for disease detection.

bioinformatics↗