Biology subjects

Wong, H. Y.

Publications and source records attributed to Wong, H. Y..

4 recordsLinked to original sources

bioRxiv2024

Ethanol down-regulates gastrula gene expression and cell movement, causing symptoms of foetal alcohol spectrum disorders

Foetal alcohol spectrum disorders (FASDs) occur in embryos when they are exposed to maternally supplied alcohol. To study the mechanisms of FASDs, the zebrafish embryo can serve as an excellent model as ethanol exposed zebrafish embryos exhibit common symptoms of human FASDs including microcephaly, incomplete neural plate closure, eye defects, craniofacial disorders and many other defects. Here we investigated the embryo development at gastrula stage when three germ layers develop with specific gene expressions and undergo dynamic cell movement including extension, convergence and epiboly, establishing the platform to form the head and body axis in the later development. Gastrula cell movement analyses using fluorescent transgenic zebrafish embryos revealed that ethanol induced dose dependent delay of extension, convergence and epiboly cell movement and associated gene expressions in all three germ layers. Our results suggest multiple targets of ethanol including gene expression and cell movement, consequently delay the key gene expression and cell localisation, causing irreversible developmental defects in the head and body axis formation.

pharmacology and toxicology↗

bioRxiv2024

A Decade of Progress: Insights of Open Data Practices in Biosciences at the University of Edinburgh

Open science promotes the accessibility of scientific research and data, emphasising transparency, reproducibility, and collaboration. This study assesses the openness and FAIRness (Findable, Accessible, Interoperable, and Reusable) of data-sharing practices within the biosciences at the University of Edinburgh from 2014 to 2023. We analysed 555 research papers across biotechnology, regenerative medicine, infectious diseases, and non-communicable diseases. Our scoring system evaluated data completeness, reusability, accessibility, and licensing, finding a progressive shift towards better data-sharing practices. The fraction of publications that share all relevant data increased significantly, from 7% in 2014 to 45% in 2023. Data involving genomic sequences were shared more frequently than image data or data on human subjects or samples. The presence of data availability statement (DAS) or preprint sharing correlated with more and better data sharing, particularly in terms of completeness. We discuss local and systemic factors underlying the current and future Open data sharing. Evaluating the automated ODDPub (Open Data Detection in Publications) tool on this manually-scored dataset demonstrated high specificity in identifying cases where no data was shared. ODDPub sensitivity improved with better documentation in the DAS. This positive trend highlights improvements in data-sharing, advocating for continued advances and addressing challenges with data types and documentation.

bioinformatics↗

bioRxiv2019

Alternative splicing modulation by G-quadruplexes

Alternative splicing is central to metazoan gene regulation but the regulatory mechanisms involved are only partially understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold both upstream and downstream of splice junctions. Analysis of in vitro G4-seq data corroborates their formation potential. G4s display the highest enrichment at weaker splice sites, which are frequently involved in alternative splicing events. The importance of G4s in RNA as supposed to DNA is emphasized by a higher enrichment for the non-template strand. To explore if G4s are involved in dynamic alternative splicing responses, we analyzed RNA-seq data from mouse and human neuronal cells treated with potassium chloride. We find that G4s are enriched at exons which were skipped following potassium ion treatment. We validate the formation of stable G4s for three candidate splice sites by circular dichroism spectroscopy, UV-melting and fluorescence measurements. Finally, we explore G4 motifs across eleven representative species, and we observe that strong enrichment at splice sites is restricted to mammals and birds.

genomics↗

bioRxiv2018

Molecular measurable residual disease testing of blood during AML cytotoxic therapy for early prediction of clinical response

AbstractO_ST_ABSPURPOSEC_ST_ABSMeasurable residual disease (MRD) testing after initial chemotherapy treatment can predict relapse and survival in AML. However, it has not been established if repeat molecular or genetic testing during chemotherapy can offer information regarding the chemotherapy sensitivity of the leukemic clone.\n\nPATIENTS AND METHODSBlood from 45 adult AML patients at day 1 and 4 of induction (n = 35) or salvage (n = 10) cytotoxic chemotherapy was collected for both quantitative real-time PCR (qPCR) assessment (WT1) and next generation sequencing (NGS, >500x depth) of 49 gene regions recurrently mutated in MDS/AML.\n\nRESULTSThe median age was 62 (23-78); 42% achieved a complete response. WT1 was overexpressed in most patients tested but was uninformative for very early MRD assessment. A median of 4 non-synonymous variants (range 0-7) were detected by DNA sequencing of blood on day 1 of therapy (median VAF: 29%). Only two patients had no variants detectable. All mutations remained detectable in blood on day 4 of intensive chemotherapy and remarkably the ratio of mutated to wild-type sequence was often maintained. This phenomenon was not limited to variants in DNMT3A, TET2 and ASXL1. The kinetics of NPM1 and TP53 variant burden early during chemotherapy appeared to be exceptions and exhibited consistent trends in this cohort.\n\nCONCLUSIONSMolecular testing of blood on day 4 of chemotherapy is not predictive of clinical response in AML. The observed stability in variant allele frequency suggests that cytotoxic therapy may have a limited therapeutic index for clones circulating in blood containing these mutations. Further validation is required to confirm the utility of monitoring NPM1 and TP53 kinetics in blood during cytotoxic therapy.

cancer biology↗