Background

Adjunctive corticosteroids in TBM treatment seem beneficial in some patients but ineffective or even harmful in others, maybe as a result of the highly variable inflammation and immunopathology in TBM.

Clinical trials have only proven the benefit of adjunctive corticosteroids on survival rate in HIV-negative patients, with no apparent reduction in long-term neurological disability and uncertain effect in HIV-infected patients. Therefore, there is a clear need to optimise host-directed therapy in TBM.

Omics are new technologies used to explore large amounts of data representing an entire set of genes or molecules, such as proteins, lipids, or metabolites, in a cell or patient. We propose to use omics studies (i.e., genomics, transcriptomics, metabolomics and proteomics) to investigate pathogenesis and treatment responses in TBM patients.

Objectives

• To define transcriptomic and metabolism in TBM & their genetic regulation using state-of-the-art LC-MS platforms and a combination of genome-wide SNP-typing of DNA from the same patient group and whole genome sequencing of a subset.
• To identify biomarkers predicting the effect of corticosteroids and discover potential new targets for host-directed therapy by integrating clinical and neuro-radiological data with CSF transcriptomics, metabolomics, and host genotype.

Study design

This study integrates data and specimens from large studies in Vietnam and Indonesia with state-of-the-art omics technology and systems biology in the Netherlands and USA, including:

• Genome-wide SNP-array;
• Whole genome sequencing;
• RNA sequencing and transcriptomics;
• Metabolomics;
• Proteomics;
• Antibodies.