Background: In silico data exploration is a key first step of exploring a research question. There are many publicly available databases and tools that offer appealing features to help with such a task. However, many applications lack exposure or are constrained with unfriendly or outdated user interfaces. Thus, it follows that there are many resources that are relevant to investigation of medical disorders that are underutilized. Results: We developed an R Shiny web application, called Kaleidoscope, to address this challenge. The application offers access to several omics databases and tools to let users explore research questions in silico . The application is designed to be user- friendly with a unified user interface, while also scalable by offering the option of uploading user-defined datasets. We demonstrate the application features with a starting query of a single gene (Disrupted in schizophrenia 1, DISC1) to assess its protein-protein interactions network. We then explore expression levels of the gene network across tissues and cell types in the brain, as well as across 34 schizophrenia versus control differential gene expression datasets. Conclusion: Kaleidoscope provides easy access to several databases and tools under a unified user interface to explore research questions in silico . The web application is open-source and freely available at https://kalganem.shinyapps.io/Kaleidoscope/ . This application streamlines the process of in silico data exploration for users and expands the efficient use of these tools to stakeholders without specific bioinformatics expertise.

Omics studies use large-scale high-throughput data to explain changes underlying different traits or conditions. However, omics analysis often results in long lists of pathways that are difficult to interpret. Therefore, it is of interest to describe a tool named PAVER (Pathway Analysis Visualization with Embedding Representations) for large scale genomic analysis. PAVER curates similar pathways into groups, identifies the pathway most representative of each group, and provides publication-ready intuitive visualizations. PAVER clusters pathways defined by their vector embedding representations and then identifies the term most cosine similar to its respective cluster’s average embedding. PAVER can integrate multiple pathway analyses, highlight relevant biological insights, and work with any pathway database.

Schizophrenia is a complex neuropsychiatric disorder with significant sex differences in onset, symptoms, and outcomes, suggesting that biological sex may influence disease mechanisms. However, molecular differences between males and females with schizophrenia remain poorly defined. This study examined sex-specific transcriptional alterations in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia using publicly available RNA-sequencing data (GSE144136). Differential gene expression (DGE) analyses were performed separately for male and female cohorts, followed by gene set enrichment analysis (GSEA), leading-edge (LE) gene analysis, and perturbagen signature matching using the Library of Integrated Network-Based Cellular Signatures (iLINCS). No genes reached significance after correction, but unadjusted analyses revealed marked sex differences. Using the uncorrected analysis, Males exhibited over 2,000 differentially expressed genes distributed evenly between up- and downregulation, whereas females showed a smaller set of differentially expressed genes that were skewed towards upregulation. Pathway-level analyses showed that males displayed upregulation of metabolic pathways and downregulation of synaptic transport processes, while females exhibited upregulation of immune pathways alongside downregulation of vesicle organization and phosphoinositide metabolism. LE gene analysis supported the pathway changes. iLINCS analysis further highlighted sex-specific drug candidates whose expression profiles were discordant schizophrenia-associated signatures. FDA approved medications with high discordance included JAK2/mTOR pathway inhibitors and metabolic regulators in males, and immune or hormonal modulators in females. Taken together, these results reveal divergent molecular signatures that may underlie sex differences in schizophrenia pathophysiology. The identification of candidate drugs with discordant transcriptomic effects suggests potential therapeutic avenues and emphasizes the importance of sex stratified approaches in schizophrenia research.

Translation: The University of Toledo Journal of Medical Sciences is the online journal launched by the University of Toledo. Manuscripts will be considered on the understanding that they report original work and are not under consideration for publication by any other journal. The journal publishes original articles reporting experimental results of basic or clinical research, case reports, and reviews. The journal uses a single blind peer review system and each manuscript, based on the results presented in its original submission, will be evaluated by two student reviewers and one faculty reviewer. This process will provide an opportunity for medical students, graduate students, residents, fellows and faculty to publish research observation in a timely manner.

Pediatric anxiety, depression, and suicide rates are on the rise across the U.S. and Ohio. This mental health crisis has placed significant burden on both the emergency department and primary care providers. The emergency department does not have the resources for the long-term care of pediatric patients struggling with mental health. Furthermore, primary care providers do not feel their training has equipped them to manage the psychiatric conditions plaguing today’s youth. To help address this crisis and decreased the number of patients resorting to emergency care, primary care and pediatric residency programs can implement seminars, simulations, and trauma-informed care trainings. Additionally, robust screening protocols, discussions about pediatric mental health in office, and increasing connections between physicians and mental health services will ensure patients are appropriately screened, diagnosed, and treated for psychiatric conditions.