Otaegui, D. | Search bioRxiv

bioRxiv2024

A proposed workflow to analyze bacterial transcripts in RNAseq from blood extracellular vesicles of people with Multiple Sclerosis

MotivationThe taxonomical characterisation of bacterial species derived from genetic material blood, including reads derived from bacterial extracellular vesicles (bEVs) poses certain challenges, such as the proper discrimination of "true" reads from contaminating reads. This is a common issue in taxa profiling and can lead to the false discovery of species that are present in the sample. To avoid such biases a careful approximation to taxa profiling is necessary. ResultsIn this work we propose a workflow to analyze the presence of bacterial transcripts as indicative of putative bEVs circulating in the blood of people with MS (pwMS). The workflow includes several reference mapping steps against the host genome and a consensus selection of genera based on different taxa profilers. The consensus selection is performed with a flagging system that removes species with low abundance or with high variation across profilers. Additionally, the inclusion of biological samples from known cultured species as well as the generation of artificial reads constitute two key aspects of this workflow. AvailabilityThe workflow is available at the following repository: https://github.com/NanoNeuro/EV_taxprofiling. Contactdavidangel.otaeguibichot@osakidetza.eus

bioinformatics↗

bioRxiv2022

Peripheral Myeloid-Derived Suppressor Cells are good biomarkers of the efficacy of Fingolimod in Multiple Sclerosis

The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition of inhibiting T cell egression from lymph nodes, fingolimod promotes the immunosuppressive activity of Myeloid-Derived Suppressor Cells (MDSCs), a cell type that can be used as a biomarker of disease severity, and of the degree of demyelination and extent of axonal damage in MS. In the present study, we have assessed whether the abundance of circulating monocytic-MDSCs (M-MDSCs) may represent a useful biomarker of fingolimod efficacy. As such, blood immune cells were analyzed at disease onset in the experimental autoimmune encephalomyelitis (EAE) MS mouse model. Fingolimod treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. The data obtained indicated that the M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e. patients who met at least two of the criteria used to define non-evidence of disease activity (NEDA-3) 12 months after treatment, providing relevant information of intention-to-treat MS patients. Collectively, our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.

immunology↗