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Biology subjects

Mason, A. L.

Publications and source records attributed to Mason, A. L..

3 recordsLinked to original sources

TransXplorer: An automated translational discovery platform for RNA-seq data

RNA-seq experiments routinely identify thousands of differentially expressed genes, but translating these into biological insights and therapeutic hypotheses often requires integrating multiple tools. Existing web platforms such as iDEP, NetworkAnalyst, and GEPIA2 address individual steps, differential expression, network visualization, or TCGA queries, but lack a unified environment spanning raw data processing to clinical and pharmacological interpretation. TransXplorer (https://transxplorer.org) is a freely available web platform that addresses this limitation by integrating the complete RNA-seq analytical workflow. It supports processing from raw FASTQ files using HISAT2 or Salmon, as well as direct GEO dataset import with automated metadata handling. Differential expression analysis is implemented via DESeq2, edgeR, and limma-voom, followed by functional enrichment across more than 1,800 species using Bioconductor resources. Batch effects are automatically detected and corrected using a composite of PVCA, kBET, and Silhouette metrics without requiring predefined batch annotations. Downstream analyses include co-expression network construction (WGCNA), protein-protein interaction mapping (STRING), cell-type deconvolution, and transcription factor inference using integrated DoRothEA and TFLink resources. The platform further links gene signatures to drug candidates through DGIdb and OpenTargets and enables survival and tumour-normal comparisons across TCGA cohorts. Application to cardiac endothelial differentiation (GSE151427) and kidney renal papillary cell carcinoma (TCGA-KIRP) datasets demonstrates accurate batch correction, biologically consistent pathway enrichment, recovery of expected cell-type proportions, and identification of clinically relevant genes and drug candidates. TransXplorer is freely available without a login.

bioinformatics↗

Sialic acid-Dependent Binding and Viral Entry of SARS-CoV-2

Emerging evidence suggests that host glycans influence infection by SARS-CoV-2. Here, we reveal that the receptor-binding domain (RBD) of the spike (S)-protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (SA), with preference for the oligosaccharide of monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind the RBD. The monomeric affinities (Kd = 100-200 M) of gangliosides for the RBD are similar to heparan sulfate, another negatively charged glycan ligand of the RBD proposed as a viral coreceptor. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to ACE2-expressing cells is decreased upon depleting cell surface SA level using three approaches: sialyltransferase inhibition, genetic knock-out of SA biosynthesis, or neuraminidase treatment. These effects on RBD binding and pseudotyped viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2.

biochemistry↗

Novel insights into the molecular heterogeneity of hepatocellularcarcinoma

Hepatocellular carcinoma (HCC) is influenced by numerous factors, which results in diverse genetic, epigenetic and transcriptional scenarios, thus posing obvious challenges for disease management. We scrutinized the molecular heterogeneity of HCC with a multi-omics approach in two small cohorts of resected and explanted livers. Whole-genome transcriptomics was conducted, including polyadenylated transcripts and micro (mi)-RNAs. Copy number variants (CNV) were inferred from whole genome low-pass sequencing data. Fifty-six cancer-related genes were screened using an oncology panel assay. HCC was associated with a dramatic transcriptional deregulation of hundreds of protein-coding genes suggesting downregulation of drugs catabolism, induction of inflammatory responses, and increased cell proliferation in resected livers. Moreover, several long non-coding RNAs and miRNAs not reported previously in the context of HCC were found deregulated. In explanted livers, downregulation of genes involved in energy-producing processes and upregulation of genes aiding in glycolysis were detected. Numerous CNV events were observed, with conspicuous hotspots on chromosomes 1 and 17. Amplifications were more common than deletions, and spanned regions containing genes potentially involved in tumorigenesis. CSF1R, FGFR3, FLT3, NPM1, PDGFRA, PTEN, SMO and TP53 were mutated in all tumors, while other 26 cancer-related genes were mutated with variable penetrance. Our results highlight a remarkable molecular heterogeneity between HCC tumors and reinforce the notion that precision medicine approaches are urgently needed for cancer treatment. We expect that our results will serve as a valuable dataset that will generate hypotheses for us or other researchers to evaluate to ultimately improve our understanding of HCC biology.

cancer biology↗