TIPS: trajectory inference of pathway significance through pseudotime comparison for functional assessment of...

Recent advances in bioinformatics analyses have led to the development of novel tools enabling the capture and trajectory mapping of single-cell RNA sequencing (scRNAseq) data. However, there is a lack of methods to assess the contributions of biological pathways and transcription factors to an overall developmental trajectory mapped from scRNAseq data. In this manuscript, we present a simplified approach for trajectory inference of pathway significance (TIPS) that leverages existing knowledgebases of functional pathways and other gene lists to provide further mechanistic insights into a biological process. TIPS identifies key pathways which contribute to a process of interest, as well as the individual genes that best reflect these changes. TIPS also provides insight into the relative timing of pathway changes, as well as a suite of visualizations to enable simplified data interpretation of scRNAseq libraries generated using a wide range of techniques. The TIPS package can be run through either a web server or downloaded as a user-friendly GUI run in R, and may serve as a useful tool to help biologists perform deeper functional analyses and visualization of their single-cell data.