Biology subjects

Armit, C.

Publications and source records attributed to Armit, C..

4 recordsLinked to original sources

bioRxiv2022

Integrated analysis of Wnt signalling system component gene expression

Wnt signalling controls patterning and differentiation across many tissues and organs of the developing embryo via temporally and spatially restricted expression of multi-gene families encoding ligands, receptors, pathway modulators and intracellular components. Here we report an integrated analysis of key encoding genes in the 3D space of the mouse embryo across multiple stages of development. We applied a method for 3D/3D image transformation to map all gene expression patterns to a single reference embryo for each stage providing both visual analysis and volumetric mapping allowing computational methods to interrogate the combined expression patterns. We identify novel territories where multiple Wnt and Fzd genes are co-expressed and cross-compare all patterns, including all seven Wnt paralogous gene pairs. The comprehensive analysis allows regions in the embryo where no Wnt or Fzd gene expression is detected, and where single Wnt genes are uniquely expressed, to be revealed. This work provides insight into a level of organisation of the patterns not previously possible, as well as presenting a resource that can be utilised further by the research community for whole system analysis.

developmental biology↗

bioRxiv2022

WlzWarp: An Open-Source Tool for Complex Alignment of Spatial Data

BackgroundThe spatio-temporal organisation of many biological processes such as gene-expression and neuronal activity is critical to understanding the overall biological behaviour, phenotype and disease. This is especially true during embryonic development. During development spatial patterns of gene expression are key to segmentation, tissue differentiation and organ development. In situ techniques can reveal the activity of genes and the presence of proteins to a very high sub-cellular resolution but typically at high resolution only a few probes can be used on any sample therefore to compare many such patterns requires mapping of image-based data to a standard spatial framework. Once mapped those data can be collated, queried and analysed in purely spatial terms to reveal unknown combinatorial gene-activity that could not be discovered any other way. Mapping spatial data to image domains with systematic variation in shape and pose, such as embryos or elongated organs, presents special problems. Automated techniques available for more constrained systems can not deliver the mapping fidelity required to analyse these data therefore we have developed a manual editing tool, WlzWarp, for mapping 3D image data using the constrained distance transform (CDT) which uniquely can deliver the complex transforms required. ResultsWe have implemented a fully open-source tool (available on GitHub), WlzWarp to provide interactive complex spatial mapping of 3D image data. We have applied WlzWarp to map a set of gene-expression patterns in the developing mouse embryo that could not be mapped by any other technique. The transform procedure was tested by using multiple images of the same gene from independent samples and thereby testing the full end-to-end mapping process. WlzWarp is implemented in C++ using open-source packages Qt, Coin and SIMVoleon for cross-architecture compatibility. It has been developed under Linux but also tested on Mac OSX and MS Windows. ConclusionsWlzWarp is a freely available software tool for non-linear registration and alignment of complex 2D & 3D spatial patterns from one image to another or to an atlas model. It has been tested in the context of embryo data but can be used for any 3D or 2D image registration problem.

bioinformatics↗

bioRxiv2020

Spatial Transcriptional Mapping of the Human Nephrogenic Program

Congenital abnormalities of the kidney and urinary tract are amongst the most common birth defects affecting 3% of newborns. The human kidney develops over a 30-week period in which a nephron progenitor pool gives rise to around a million nephrons. To establish a framework for human nephrogenesis, we spatially resolved a stereotypical process by which equipotent nephron progenitors generate a nephron anlagen, then applied data-driven approaches to construct three-dimensional protein maps on anatomical models of the nephrogenic program. Single cell RNA sequencing identified novel progenitor states which were spatially mapped to the nephron anatomy enabling the generation of functional gene-networks predicting interactions within and between nephron cell-types. Network mining identified known developmental disease genes and predicts new targets of interest. The spatially resolved nephrogenic program made available through the Human Nephrogenesis Atlas (https://sckidney.flatironinstitute.org/) will facilitate an understanding of kidney development and disease, and enhance efforts to generate new kidney structures.

cell biology↗

bioRxiv2018

Increased Interactivity and Improvements to the GigaScience Database, GigaDB.

With a large increase in the volume and type of data archived in GigaDB since its launch in 2011, we have studied the metrics and user patterns to assess the important aspects needed to best suit current and future use. This has led to new front-end developments and enhanced interactivity and functionality that greatly improves user experience. In this article, we present an overview of the current practices including the Biocurational role of the GigaDB staff, the broad usage metrics of GigaDB datasets, and an update on how the GigaDB platform has been overhauled and enhanced to improve the stability and functionality of the codebase. Finally, we report on future directions for the GigaDB resource.

scientific communication and education↗