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Selvaraj, B.

Publications and source records attributed to Selvaraj, B..

2 recordsLinked to original sources

Astrocytes control motor neuronal mitochondrial axonal transport deficits in C9ORF72 ALS.

Disrupted axonal transport and astrocyte dysfunction are implicated in amyotrophic lateral sclerosis (ALS). Here, we show these are intrinsically linked: human induced pluripotent stem cell-derived astrocytes carrying the C9ORF72 mutation disrupt axonal transport and mitochondrial function in motor neurons (MNs). Conversely, either isogenic gene-corrected astrocytes or selectively boosting C9ORF72-astrocyte mitochondrial bioenergetics rescue axonal transport deficits in C9ORF72-MNs. Thus, astrocytes have a dominant effect on axonal mitochondrial transport in the context of ALS.

neuroscience↗

An Unsupervised Graph Embeddings Approach to Multiplex Immunofluorescence Image Exploration

Understanding the complex biology of the tumor microenvironment (TME) is necessary to understand the mechanisms of action of immuno-oncology therapies and to match the right therapies to the right patients. Multiplex immunofluorescence (mIF) is a useful technology that has tremendous potential to further our understanding of cancer patho-biology; however, tools that fully leverage the high dimensionality of this data are still in their infancy. We describe here a novel deep learning pipeline aimed to allow Graph-based Inspection of Tissues via Embeddings, GraphITE. GraphITE transforms mIF data into a graph representation, where unsupervised learning algorithms can be utilised to generate embeddings representing cellular neighbourhoods. The embeddings can be downprojected and explored for clustering analysis, and patterns can be mapped back to the image as well as interrogated for phenotypical, morphological, or structural distinctiveness. GraphITE supports the extraction of information not only on the phenotypes of individual cells or the relationships between specific cell types, but is able to characterize cell neighborhoods to look for more complex interactions, thereby allowing pathologists and data scientists to explore mIF data sets, uncovering patterns that are otherwise obscured by the high-dimensionality of the data. In this work, we showcase the current setup of the system, going from raw input data all the way to a user friendly exploration tool. Using this tool, we show how the data can be navigated in a way previously not possible.

pathology↗