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Biology subjects

Elkjaer, M. L.

Publications and source records attributed to Elkjaer, M. L..

3 recordsLinked to original sources

Bridging the 3D geometrical organisation of white matter pathways across anatomical length scales and species

We used diffusion MRI and x-ray synchrotron imaging on monkey and mice brains to examine the organisation of fibre pathways in white matter across anatomical scales. We compared the structure in the corpus callosum and crossing fibre regions and investigated the differences in cuprizone-induced demyelination mouse brains versus healthy controls. Our findings revealed common principles of fibre organisation that apply despite the varying patterns observed across species; small axonal fasciculi and major bundles formed laminar structures with varying angles, according to the characteristics of major pathways. Fasciculi exhibited non-straight paths around obstacles like blood vessels, comparable across the samples of varying fibre complexity and demyelination. Quantifications of fibre orientation distributions were consistent across anatomical length scales and modalities, whereas tissue anisotropy had a more complex relationship, both dependent on the field-of-view. Our study emphasises the need to balance field-of-view and voxel size when characterising white matter features across length scales.

neuroscience↗

Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases

Alternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis of AS-set events are lacking. To mitigate this, we developed NEASE, a tool integrating pathways with protein-protein and domain-domain interactions to functionally characterize AS events. We show in four application cases how NEASE can identify pathways contributing to tissue identity and cell type development, and how it highlights splicing-related biomarkers. With a unique view on AS, NEASE generates unique and meaningful biological insights complementary to classical pathways analysis.

bioinformatics↗

MS Atlas - A molecular map of brain lesion stages in progressive multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder of the central nervous system with an untreatable late progressive phase in a high percentage of patients. Molecular maps of different stages of brain lesion evolution in patients with progressive MS (PMS) are missing but critical for understanding disease development and to identify novel targets to halt progression. We introduce the first MS brain lesion atlas (msatlas.dk), developed to address the current challenges of understanding mechanisms driving the fate of PMS on lesion basis. The MS Atlas gives means for testing research hypotheses, validating candidate biomarkers and drug targets. The MS Atlas data base comprises comprehensive high-quality transcriptomic profiles of 73 brain white matter lesions at different stages of lesion evolution from 10 PMS patients and 25 control white matter samples from five patients with non-neurological disease. The MS Atlas was assembled from next generation RNA sequencing of post mortem samples using strict, conservative preprocessing as well as advanced statistical data analysis. It comes with a user-friendly web interface, which allows for querying and interactively analyzing the PMS lesion evolution. It fosters bioinformatics methods for de novo network enrichment to extract mechanistic markers for specific lesion types and pathway-based lesion type comparison. We describe examples of how the MS Atlas can be used to extract systems medicine signatures. We also demonstrate how its interface can interactively condense and visualize the atlas content. This compendium of mechanistic PMS white matter lesion profiles is an invaluable resource to fuel future multiple sclerosis research and a new basis for treatment development.

systems biology↗