Biology subjects

O'Sullivan, D.

Publications and source records attributed to O'Sullivan, D..

4 recordsLinked to original sources

bioRxiv2022

Mining impactful discoveries from the biomedical literature

MotivationLiterature-Based Discovery (LBD) aims to help researchers to identify relations between concepts which are worthy of further investigation by text-mining the biomedical literature. While the LBD literature is rich and the field is considered mature, standard practice in the evaluation of LBD methods is methodologically poor and has not progressed on par with the domain. The lack of properly designed and decent-sized benchmark dataset hinders the progress of the field and its development into applications usable by biomedical experts. ResultsThis work presents a method for mining past discoveries from the biomedical literature. It leverages the impact made by a discovery, using descriptive statistics to detect surges in the prevalence of a relation across time. This method allows the collection of a large amount of time-stamped discoveries which can be used for LBD evaluation or other applications. The validity of the method is tested against a baseline representing the state of the art "time sliced" method. AvailabilityThe source data used in this article are publicly available. The implementation and the resulting data are published under open-source license: https://github.com/erwanm/medline-discoveries (code) https://zenodo.org/record/5888572 (datasets). An online exploration tool is also provided at https://brainmend.adaptcentre.ie/. Contacterwan.moreau@adaptcentre.ie

bioinformatics↗

bioRxiv2022

In macrophages fatty acid oxidation spares glutamate for use in diverse metabolic pathways required for alternative activation

Fatty acid oxidation (FAO) is upregulated in IL-4-stimulated (alternatively activated) macrophages (M(IL-4)). We examined the effect of loss of function of the enzyme Cpt1a, which facilitates the entry of long chain fatty acids (FA) into mitochondria for FAO, on alternative activation. Expression of M(IL-4) markers ARG1, CD301 and RELM, was impaired in tamoxifen-treated ERT2Cre x Cpt1afl/fl macrophages and in macrophages expressing shRNA targeting Cpt1a (Cpt1a-shRNA). In contrast, VaviCre x Cpt1afl/fl and LysmCre x Cpt1afl/fl M(IL-4) responded normally to IL-4. Reduced alternative activation due to Cpt1a loss of function was linked to decreased cellular pools of -ketoglutarate, glutamate, and glutathione, diminished commitment of glucose carbon to serine/glycine synthesis, and decreased expression of genes in the Nrf2-oxidative stress response pathway. Consistent with this, reactive oxygen species were increased. Restoration of glutathione pools with N-acetyl cysteine normalized oxidative stress and allowed alternative activation in the face of Cpt1a-deficiency, pointing to a role for FAO in the control of ROS and as being important for alternative activation. In VaviCre x Cpt1afl/fl M(IL-4), glutamine uptake was increased, compensating for the loss of FAO to meet necessary metabolic demands, to allow alternative activation. The data indicate that macrophages are able to regulate glutamine metabolism to compensate for chronic disruption of FAO to meet metabolic needs.

immunology↗

bioRxiv2021

Literature-Based Discovery beyond the ABC paradigm: a contrastive approach

Literature-Based Discovery (LBD) aims to help researchers to identify relations between concepts which are worthy of further investigation by text-mining the biomedical literature. The vast majority of the LBD research follows the ABC model: a relation (A,C) is a candidate for discovery if there is some intermediate concept B which is related to both A and C. The ABC model has been successful in applications where the search space is strongly constrained, but there is limited evidence about its usefulness when applied in a broader context. Through a case study of 8 recent discoveries related to neurodegenerative diseases (NDs), we show the limitations of the ABC model in an open-ended context. The study emphasizes the impact of the choice of source data and extraction method on the resulting knowledge base: different "views" of the biomedical literature offer different levels of accuracy and coverage. We propose a novel contrastive approach which leverages these differences between "views" in order to target relations between concepts of interest. We explore various parameters and demonstrate the relevance of our approach through quantitative evaluation on the 8 target discoveries. The source data used in this article are publicly available. The different parts of the software used to process the data are published under open-source license and provided with detailed instructions. The main code for this paper is available at https://github.com/erwanm/lbd-contrast (required dependencies are detailed in the documentation). A prototype of the system is also provided as an online exploration tool at brainmend.adaptcentre.ie.

bioinformatics↗

bioRxiv2020

Comparison of SARS-CoV2 N gene real-time RT-PCR targets and commercially available mastermixes

We aim to test four one-step RT real-time mastermix options for use in SARS-CoV2 real-time PCR, with three primer/probe assays targeting the N gene. The lower limit of detection is determined using a SARS CoV2 N gene RNA transcript dilution series (to 1 copy/{micro}l) and verified using 74 nose and throat swabs. The N2 assay demonstrates the most sensitive detection of SARS-Cov-2 RNA. Three of the four mastermixes performed well, with the Takara One Step PrimeScript III RT-PCR Kit mastermix demonstrating improved performance at the lower limit of detection.

microbiology↗