Analysis of gene and isoform expression levels is becoming critical for the detailed understanding of biochemical mechanisms. In addition, integrating RNA-seq data with other omics data types, such as proteomics and metabolomics, provides a strong approach for consolidating our understanding of biological processes across various organizational tiers, thus promoting the identification of potential therapeutic targets. We present our pipeline, called MultiOmicsIntegrator (MOI), an inclusive pipeline for comprehensive omics analyses. MOI represents a unified approach that performs in-depth individual analyses of diverse omics. Specifically, exhaustive analysis of RNA-seq data at the level of genes, isoforms of genes as well as miRNA is offered, coupled with functional annotation and structure prediction of these transcripts. Additionally, proteomics and metabolomics data are supported providing a holistic view of biological systems. Finally, MOI has tools to integrate simultaneously multiple and diverse omics datasets, with both data and functional driven approaches, fostering a deeper understanding of intricate biological interactions. MOI and ReadTheDocs. Supplementary data are available at Bioinformatics Advances online.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It primarily affects the motor system but is also associated with a range of cognitive impairments that can manifest early in disease progression, indicating its multifaceted nature. In this paper, we performed a meta-analysis of transcriptomics and proteomics data using MultiOmicsIntegrator to gain insights into the post-transcriptional modifications and deregulated pathways associated with this disease. Our results reveal differential isoform usage between control and PD patient brain samples that result in enriched alternative splicing events, including an extended UTR length, domain loss, and the upregulation of non-coding isoforms. We found that Inositol-Requiring Enzyme 1 (IRE1) is active in PD samples and examined the role of its downstream signaling through X-box binding mRNA 1 (XBP1) and regulated IRE1-dependent decay (RIDD). We identified several RIDD candidates and showed that the enriched alternative splicing events observed are associated with RIDD. Moreover, in vitro mRNA cleavage assays demonstrated that OSBPL3, C16orf74, and SLC6A1 mRNAs are targets of IRE1 RNAse activity. Finally, a pathway enrichment analysis of both XBP1s and RIDD targets in the PD samples uncovered associations with processes such as immune response, oxidative stress, signal transduction, and cell–cell communication that have previously been linked to PD. These findings highlight a potential regulatory role of IRE in PD.