Umran Yaman from the UK Dementia Research Institute at University College London in the UK presented at London Calling 2024 on “Long-read transcriptomics shows synaptic adaptation to amyloid pathology in Alzheimer’s.” Yaman is a Ph.D. candidate and described how the accumulation of amyloid drives microglial activation. They performed long-read sequencing of cDNA from mice. They used tissue from the cortex and the PCR cDNA sequencing kit SQK-PCB109 with PromethION flow cells (R9.4.1). The pipeline they used was the pre-processing workflow recommended by Nanopore: trimming and orientation were performed with Pychopper, mapping was conducted with Minimap2, and transcriptome assembly was done with StringTie. Next, an external database was used to identify protein domains, signal peptides, and other predictions. Isoform switching and usage events were detected using the long reads obtained. Alternative splicing and transcript isoform, as well as exon usage, were profiled. There were differences in the transcript composition and usage compared to the control samples. For example, gene transcript isoforms that had similar patterns were identified. Yaman said novel isoform-switching events were found. They noted there were also differences between male and female mice. A splicing-based analysis in response to amyloid identified alternative splicing events compared to the controls. Their results suggested that amyloid and microglial risk genes identified by GWAS may also present synaptic adaptation by splicing during disease progression. While I don’t understand the details of the synaptic adaptation hypothesis, I appreciate the use of long-read sequencing and splicing-based analysis to identify isoform-switching events. I am curious about how to apply some of these techniques to prokaryotic systems and host-microbe interactions.
