GSE98739 RNA-seq dataset for Identifying Novel Therapeutic Targets by Combining Transcriptional Data with Ordinal Clinical Measurements

We report an analytical approach to integrate ordinal clinical information with transcriptomics. We have applied this method to public data for a large cohort of Huntington ’s disease patients and controls, identifying and prioritizing phenotype-associated genes. To validate the approach, we have performed viability, siRNA knockdown, mRNA-seq, and ChIP-seq on striatal precursor cells expressing either full-length wild type (STHdh Q7) or mutant huntingtin (STHdh Q111) . We have verified the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrated that inhibiting the enzyme, SPL, has neuroprotective effects in HD models. We have shown that one consequence of inhibiting SPL is the intracellular inhibition of HDACs, thus linking our observations in sphingolipid metabolism to a well-characterized HD pathway. Our approach is easily applied to any data with ordinal clinical measurements, and may deepen our understanding of disease processes.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research