Biology subjects

Thaventhiran, J. E.

Publications and source records attributed to Thaventhiran, J. E..

3 recordsLinked to original sources

bioRxiv2025

Near-cognate tRNAs dominate codon decoding times in simulated ribosomes

The codon sequence of messenger RNAs affects ribosome dynamics, translational control, and transcript stability. Here we describe an advanced computational modelling tool and its application to studying the effect of different tRNA species on the codon decoding process. We show that simulated codon decoding times are sensitive to the abundance of near-cognate tRNA species as well as cognate species, an aspect of the decoding system that is not fully considered in other computational modelling studies. We demonstrate that codon decoding times predicted by models that accurately define near-cognate tRNAs and that are parameterised with high-quality tRNA abundance datasets are highly similar to ribosome dwell times determined using experimental ribosome footprinting data, thereby confirming both the importance of near-cognate tRNAs for the codon decoding process and the general accuracy of our modelling tools.

systems biology↗

bioRxiv2023

Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals

The bidirectional interaction between the immune system and the gut microbiota is a key contributor to various host physiological functions. Immune-associated diseases such as cancer and autoimmunity, as well as the efficacy of immunomodulatory therapies, have been linked to microbiome variation. While COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunomodulating therapies. We find that the gut microbiome remained remarkably stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results indicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings encourage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.

microbiology↗

bioRxiv2018

GRID - Genomics of Rare Immune Disorders: a highly sensitive and specific diagnostic gene panel for patients with primary immunodeficiencies

Primary Immune disorders affect 15,000 new patients every year in Europe. Genetic tests are usually performed on a single or very limited number of genes leaving the majority of patients without a genetic diagnosis. We designed, optimised and validated a new clinical diagnostic platform called GRID, Genomics of Rare Immune Disorders, to screen in parallel 279 genes, including 2015 IUIS genes, known to be causative of Primary Immune disorders (PID). Validation to clinical standard using more than 58,000 variants in 176 PID patients shows an excellent sensitivity, specificity. The customised and automated bioinformatics pipeline prioritises and reports pertinent Single Nucleotide Variants (SNVs), INsertions and DELetions (INDELs) as well as Copy Number Variants (CNVs). An example of the clinical utility of the GRID panel, is represented by a patient initially diagnosed with X-linked agammaglobulinemia due to a missense variant in the BTK gene with severe inflammatory bowel disease. GRID results identified two additional compound heterozygous variants in IL17RC, potentially driving the altered phenotype.

genomics↗