Fig. 1: Methodological overview.

A An overview of the experimental approach used to profile isoform diversity in (i) the rTg4510 mouse model using short-read RNA-Seq (Illumina), long-read whole transcriptome and targeted Iso-Seq (PacBio) and long-read nanopore cDNA sequencing (ONT) from bulk cortex tissue and FANS-isolated nuclei populations and (ii) post-mortem human cortex tissue from individuals with high and low AD neuropathology using long-read targeted nanopore cDNA sequencing (ONT). Further details on all samples used in this study can be found in Methods, Supplementary Data 1 and Supplementary Data 2. B An overview of the bioinformatics pipeline used to process, align, quantify, annotate and characterize full-length transcript reads. Further details are provided in Methods. C An overview of the FICLE bioinformatics tool developed as part of this work to comprehensively characterize and visualize targeted long-read RNA sequencing data. AD Alzheimer’s disease, AS alternative splicing, CCS circular consequence sequence, CTX cortex, ECX entorhinal cortex, FANS fluorescence-activated nuclei sorting, FL full-length, NeuN neuronal nuclear protein, HQ high-quality, LR long-read, ONT Oxford Nanopore Technologies, PacBio Pacific Biosciences, WT wild-type mice, TG rTg4510 transgenic mice.