Multi-omics and transcriptomic profiling of anesthetic response reveals RNA regulatory networks in postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) are still significant issues in the perioperative care that impact patient recovery and satisfaction, but the underlying molecular pathways that lead to personal predisposition are not comprehensively understood. In order to fill this gap we performed a multi-omics study incorporating bulk RNA sequencing, single cell transcriptomics, circRNA profiling, and alternative splicing evaluation and genotype expression colocalization analyses to detail regulatory networks of PONV. Analysis of differential expression showed inflammatory pathways and neurotransmission pathways as key driving factors in the development of symptoms, and HIF1A and STAT3 were found to be prominent central nodes in a variety of data layers. Cell type-specific transcriptional signatures indicative of neuroimmune interaction as a driving force were identified at the single-cell level with regulatory noncoding elements including differentiation of back-splice junction support of circPTGS2 and circGABRA3 and alternative splicing of GABRA3 indicating further post-transcriptional regulation. Convergent molecular signals were observed between matched datasets of patients with Integration of bulk and single-cell expression with BisqueRNA deconvolution and Harmony batch correction. These results present the initial transcriptomics-wide multi-dimensional model to integrate genetic variation, RNA organization and cellular heterogeneity to describe PONV susceptibility. The paper is supporting the sale of potential biomarker(s) that promise to inform any future clinical prediction framework and tailored antiemetic alternatives, which forms the basis of translating to diagnostic and therapeutic uses. Clinical implementation will be provided with further validation, such as protein-level validation and splice variants PCR confirmation and increased multicentric cohorts.