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Biology subjects

O'Callaghan, A.

Publications and source records attributed to O'Callaghan, A..

4 recordsLinked to original sources

A novel channel invariant architecture for the segmentation of cells and nuclei in multiplexed images using InstanSeg

The quantitative analysis of bioimaging data increasingly depends on the accurate segmentation of cells and nuclei, a significant challenge for the analysis of high-plex imaging data. Current deep learning-based approaches to segment cells in multiplexed images require reducing the input to a small and fixed number of input channels, discarding imaging information in the process. We present Channel Net, a novel deep learning architecture for generating three-channel representations of multiplexed images irrespective of the number or ordering of imaged biomarkers. When combined with InstanSeg, ChannelNet sets a new benchmark for the segmentation of cells and nuclei on public multiplexed imaging datasets. We provide an open implementation of our method and integrate it in open source software. Our code and models are available on https://github.com/instanseg/instanseg.

bioinformatics↗

GelGenie: an AI-powered framework for gel electrophoresis image analysis

Gel electrophoresis is a ubiquitous laboratory method for the separation and semi-quantitative analysis of biomolecules. However, gel image analysis principles have barely advanced for decades, in stark contrast to other fields where AI has revolutionised data processing. Here, we show that an AI-based system can automatically identify gel bands in seconds for a wide range of experimental conditions, far surpassing the capabilities of current software. We used a dataset containing 500+ images of manually-labelled gels to train various U-Nets to accurately identify bands through segmentation, i.e. classifying pixels as band or background. When applied to gel electrophoresis data from other laboratories, our system generated results that quantitatively matched those of the original authors. We have publicly released our models through GelGenie, an open-source application that allows users to extract bands from gel images on their own devices, with no expert knowledge or experience required.

molecular biology↗

Transcriptional dynamics of colorectal cancer risk associated variation at 11q23.1 are correlated with tuft cell abundance and marker expression in silico

Colorectal cancer (CRC) is characterised by heritable risk that is not well understood. Heritable, genetic variation at 11q23.1 is associated with increased colorectal cancer (CRC) risk, demonstrating eQTL effects on 3 cis- and 23 trans-eQTL targets. We sought to determine the relationship between 11q23.1 cis- and trans-eQTL target expression and test for potential cell-specificity. scRNAseq from 32,361 healthy colonic epithelial cells was aggregated and subject to weighted gene co-expression network analysis (WGCNA). One module (blue) included 19 trans-eQTL targets and was correlated with C11orf53 expression only. Following unsupervised clustering of single cells, the expression of 19 trans-eQTL targets was greatest and most variable in cluster number 11, which transcriptionally resembled tuft cells. 14 trans-eQTL targets were found to demarcate this cluster, 11 of which were corroborated in a second dataset. Intra-cluster WGCNA and module preservation analysis then identified twelve 11q23.1 trans-eQTL targets to comprise a network that was specific to cluster 11. Finally, linear modelling and differential abundance testing showed 11q23.1 trans-eQTL target expression was predictive of cluster 11 abundance. Our findings suggest 11q23.1 trans-eQTL targets comprise a C11orf53-related network that is likely tuft cell-specific and reduced expression of these genes correlates with reduced tuft cell abundance in silico.

bioinformatics↗

Long-term consolidation switches goal proximity coding from hippocampus to retrosplenial cortex

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (> 2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the proximity to the goal in the newly learned campus, but not in the familiar campus. By contrast retrosplenial cortex tracked the distance to the goal in the familiar campus, but not in the recently learned campus. These responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and help advance models of how neural circuits support navigation in novel and highly familiar environments.\n\nSignificance StatementHistorically, research on the hippocampal formation has focused on its role in long-term memory and navigation - often in isolation. No study to date has directly compared realistic navigation within familiar with recently learned environments, nor has it been explored how the neural substrates, along with computational codes, may change. In this study, we show for the first time, a shift from hippocampal to cortical coding of distance to a goal during active navigation. This study bridges the gap between memory consolidation and navigation, and paves the way for more functional and realistic understanding of the hippocampus.

neuroscience↗