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Biology subjects

Lim, Y. Y.

Publications and source records attributed to Lim, Y. Y..

4 recordsLinked to original sources

Bacterial Stress Responses Lower mRNA-Protein Level Correlations

Diverse bacterial pathogens have evolved complex regulatory mechanisms to adapt to various environmental stresses during infection. The uncertainty in mRNA-protein levels in response to environmental stressors complicates our understanding of bacterial physiology and their adaptation to stressful environments. To examine this issue, we have integrated transcriptomics and proteomics data on three human bacterial pathogens Salmonella enterica Typhimurium, Yersinia pseudotuberculosis, and Staphylococcus aureus under ten infection-relevant stress conditions. We observed positive correlations between mRNA and protein levels, which were decreased under different stress conditions. Essential genes exhibited higher expression levels with lower variation across the conditions and stronger mRNA-protein correlations compared to non-essential genes, highlighting their critical role in bacterial adaptability and survival. Moreover, we identified a substantial number of genes with stress-induced non-correlating mRNA-protein levels, especially under conditions triggering strong stress responses. Particularly this level was dramatically lowered for osmotic stress specific genes affected by impaired translational activity under osmotic stress. Our findings highlight the prevalence of non-correlating mRNA-protein levels and the potential role of post-translational modifications in modulating protein levels in response to environmental stressors during infection. This study provides a comprehensive framework for integrating transcriptomics and proteomics data and identifies potential gene products that might significantly impact the ability of diverse bacterial pathogens to adapt to hostile infection environments. Significance StatementUnderstanding how bacteria adapt to host environments is crucial for combating infections. We employed an integrative transcriptomics and proteomics approach to investigate mRNA-protein correlations in three clinically relevant pathogens under ten infection-relevant stress conditions. We identified genes whose mRNA-protein relationships are significantly disrupted by specific stressors. This study provides a deeper understanding of mRNA-protein level uncertainty, coupling it to stress responses known to trigger critical post-transcriptional and post-translational regulations. These findings help reveal novel mechanisms of bacterial adaptation and pathogenesis. By providing a comprehensive, multi-species dataset, this study serves as a foundational resource for infection biology, driving future advancements in understanding complex regulatory networks and identifying potential antimicrobial targets.

microbiology↗

ShinyCell2: An extended library for simple and sharable visualisation of spatial, peak-based and multi-omic single-cell data

Single-cell technologies now span multiple modalities, generating large, complex datasets that challenge analysis and sharing. We present ShinyCell2, an enhanced R package for interactive visualisation of single-cell multi-omics and spatial transcriptomics data. ShinyCell2 retains the simplicity and lightweight deployment of its predecessor while introducing advanced visualisations, cross-modality comparisons, and statistical tools tailored to spatial and multi-omic data. It enables intuitive, rapid exploration of high-dimensional data without requiring extensive computational expertise.

bioinformatics↗

Modelling dynamics of human NDPK hexamer structure, stability and interactions

Nucleoside diphosphate kinases (NDPKs) are evolutionarily conserved multifunctional enzymes involved in energy metabolism and gene regulation. NDPKs primarily regulate nucleotide pool turnover by catalyzing the transfer between nucleoside triphosphate (NTPs) and their deoxy derivatives, maintaining cellular homeostasis. The NDPK hexameric assembly is needed for kinase activity, but its precise assembly into homo-/hetero-oligomeric complexes remains poorly understood. How quaternary structure affects NDPK activity is limited by high subunit homology, experimental challenges in isolating in vivo heterohexamers and subunit abundances across cellular compartments. We identify conserved Arg27 across group I NDPKs (NME1-4) as the key residue for hexamer assembly. The Arg27 ensures similar hexameric assembly across subunits and mediates inter- and intra-molecular monomeric interactions, while Arg27 mutation leads to decreased binding affinity, dynamics, and complex destabilization. The double and triple Arg NME4 mutations destabilize hexamer into dimer due to shorter C-terminal region. Simulating NME1-3 with Arg mutations and shortened C-terminal recapitulates hexameric destabilization, highlighting role of the C-terminal region in stabilizing NDPK hexamers. Comparing heterohexameric complexes, we report NME1-NME2 (A1B5) complex as most stable and abundant, owing to predominant subunit nuclear localization. We propose that Arginine residues, C-terminal sequence and subunit abundances contribute to formation and stabilization of NDPK heterohexameric complexes.

bioinformatics↗

Protist.guru: a comparative transcriptomics database for the protist kingdom

SummaryDuring the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still neglected. To address this gap, we used gene expression data from 15 distinct protist species to create protist.guru: an online database equipped with tools for identifying functional co-expression networks, gene families, and enriched gene clusters. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AvailabilityThe database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.

evolutionary biology↗