Nadia Davidson from The Walter and Eliza Hall Institute in Australia presented at London Calling 2025. The intriguing title of the session was “Blessy: enabling differential analysis of phased protein domains.” Blessy is a new tool from Davidson’s research group. Davidson spoke about the impact of alternative splicing on protein function. Davidson and team used long-reads and mapped them. Using quantification and statistical testing, the team made sense of the data with protein analyses. Davidson then analyzed the removal or inclusion of domains through splicing. The research team mapped protein domains to transcripts. The domain combination (DoCo) quantification can help better understand the biological information. Blessy is an open source R package that takes differential DoCO for analysis. It automatically annotates features onto transcripts. To test Blessy, the team took 200 genes and simulated and compared analyses, validating the accuracy and low false-positives of the Blessy package/system. Next, the research team used single-cell datasets to test Blessy. The single-cell pipeline starts with Flexiplex, a tool the group developed for barcode discovery. Next, Nailpolish, a new tool from the group, performs duplicate consensus calling. Minimap2 is used for alignment and Oarfish does quantification. Blessy is then used for DoCo aggregation and Seurat performs clustering and visualization. Isopod is used for differential usage testing. Davidson ended by requesting feedback and testing of Blessy from the community. It will be interesting to learn what happens with this approach!
