Biology subjects

O'Shea, K.

Publications and source records attributed to O'Shea, K..

3 recordsLinked to original sources

bioRxiv2025

Dissection of ergosterol metabolism reveals a pathway optimized for membrane phase separation

Sterols are among the most abundant lipids in eukaryotic cells, yet are synthesized through notoriously long metabolic pathways. It has been proposed that the molecular evolution of such pathways must have required each step to increase the capacity of its product to condense and order phospholipids. Here we carry out a systematic analysis of the ergosterol pathway that leverages the yeast vacuoles capacity to phase-separate as a predictive biophysical readout for each intermediate. In the post-synthetic steps specific to ergosterol biosynthesis, we find that successive modifications act to oscillate ordering capacity, settling on a level that supports phase separation while retaining fluidity of the resulting domains. Simulations carried out with each intermediate showed how conformers in the sterols alkyl tail are capable of modulating long-range ordering of phospholipids, which could underlie changes in phase behavior. Our results indicate that the complexity of sterol metabolism could have resulted from the need to balance lipid interactions required for membrane organization.

biophysics↗

bioRxiv2021

SPOROS: A pipeline to analyze DISE/6mer seed toxicity

micro(mi)RNAs are (18-22nt long) noncoding short (s)RNAs that suppress gene expression by targeting the 3 untranslated region of target mRNAs. This occurs through the seed sequence located in position 2-7/8 of the miRNA guide strand, once it is loaded into the RNA induced silencing complex (RISC). G-rich 6mer seed sequences can kill cells by targeting C-rich 6mer seed matches located in genes that are critical for cell survival. This results in induction of Death Induced by Survival gene Elimination (DISE), also referred to as 6mer seed toxicity. miRNAs are often quantified in cells by aligning the reads from small (sm)RNA sequencing to the genome. However, the analysis of any smRNA Seq data set for 6mer seed toxicity requires an advanced workflow, solely based on the exact position 2-7 of any sRNA that can enter the RISC. Therefore, we developed SPOROS, an automated pipeline that produces multiple useful outputs to compare 6mer seed toxicity of all cellular sRNAs, regardless of their nature, between different samples. We provide two examples to illustrate the capabilities of SPOROS: Example one involves the analysis of RISC-bound sRNAs in a cancer cell line (either wild-type or two mutant lines unable to produce most miRNAs). Example two is based on a publicly available smRNA Seq data set from postmortem brains (either from normal or Alzheimers patients). Our methods are designed to be used to analyze a variety of smRNA Seq data in various normal and disease settings.

bioinformatics↗

bioRxiv2018

DIMEdb: an integrated database and web service for metabolite identification in direct infusion mass spectrometery

MotivationMetabolomics involves the characterisation, identification, and quantification of small molecules (metabolites) that act as the reaction intermediates of biological processes. Over the past few years, we have seen wide scale improvements in data processing, database, and statistical analysis tools. Direct infusion mass spectrometery (DIMS) is a widely used platform that is able to produce a global fingerprint of the metabolome, without the requirement of a prior chromatographic step - making it ideal for wide scale high-throughput metabolomics analysis. In spite of these developments, metabolite identification still remains a key bottleneck in untargeted mass spectrometry-based metabolomics studies. The first step of the metabolite identification task is to query masses against a metaboite database to get putative metabolite annotations. Each existing metabolite database differs in a number of aspects including coverage, format, and accessibility - often limiting the user to a rudimentary web interface. Manually combining multiple search results for a single experiment where there may be potentially hundreds of masses to investigate becomes an incredibly arduous task.\n\nResultsTo facilitate unified access to metabolite information we have created the Direct Infusion MEtabolite database (DIMEdb), a comprehensive web-based metabolite database that contains over 80,000 metabolites sourced from a number of renowned metabolite databases of which can be utilised in the analysis and annotation of DIMS data. To demostrate the efficacy of DIMEdb, a simple use case for metabolic identification is presented. DIMEdb aims to provide a single point of access to metabolite information, and hopefully facilitate the development of much needed bioinformatic tools.\n\nAvailabilityDIMEdb is freely available at https://dimedb.ibers.aber.ac.uk.\n\nContactkeo7@aber.ac.uk\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗