Yeung, H.-Y. | bioRxiv Science

bioRxiv2023

hadge: a comprehensive pipeline for donor deconvolution in single cell

Single cell multiplexing techniques (cell hashing and genetic multiplexing) allow to combine multiple samples, thereby optimizing sample processing and reducing batch effects. Cell hashing conjugates antibody-tags or chemical-oligonucleotides to cell membranes, while genetic multiplexing allows to mix genetically diverse samples and relies on aggregation of RNA reads at known genomic coordinates. We developed hadge (hashing deconvolution combined with genotype information), a Nextflow pipeline that combines 12 methods to perform both hashing- and genotype-based deconvolution. We propose a joint deconvolution strategy combining the best performing methods and we demonstrate how this approach leads to recovery of previously discarded cells in a nuclei hashing of fresh-frozen brain tissue.

bioinformatics↗

bioRxiv2022

Biochemical and metabolic maladaption defines pathological niches in progressive multiple sclerosis

Progressive multiple sclerosis (MS) is driven by demyelination, neuroaxonal loss, and mitochondrial damage occurring behind a closed blood-brain barrier (BBB).1,2 Patients with progressive MS typically fail to respond to available immunomodulatory drugs that reduce relapses in early disease.2 This indicates a dire need to identify non-canonical therapeutic avenues to limit neurodegeneration and promote protection and repair.3 Here, we have employed high-resolution multiomic profiling to characterise the biochemical and metabolic adaptations underpinning MS pathology, as these have been incompletely described but critically, may be amenable to BBB-permeable drug targeting. Using synchrotron radiation (SR)- and focal plane array (FPA)-based Fourier transform infrared microspectroscopy (FTIR), we spatially mapped the biochemical features present in human progressive MS and control post-mortem brain and rare spinal cord tissue. By employing single-nuclear RNA sequencing (snRNA-seq), 10x Genomics Visium spatial transcriptomics and spatial proteomics to resolve their cellular context, we found that these biochemical features provide a uniquely and highly disease-specific barcode for distinct pathological niches within the tissue. Characterisation of the metabolic processes underpinning these niches revealed an associated re-organisation of the astrocytic landscape in the grey and white matter, with implications for the treatment of progressive MS.

neuroscience↗