Long read, isoform aware sequencing of mouse nucleus accumbens after chronic cocaine treatment

To better understand the full-length transcriptome of the nucleus accumbens (NAc)—a key brain reward region—in chronic cocaine treatment, we perform the first single molecule, long-read sequencing analysis using the Iso-seq method to detect 42,114 unique transcripts from mouse NAc polyadenylated RNA. Using GENCODE annotation as a reference, we find that over half of the Iso-seq derived transcripts are annotated, while 46% of them harbor novel splicing events in known genes; around 1% of them correspond to other types of novel transcripts, such as fusion, antisense and intergenic. Approximately 34% of the novel transcripts are matched with a compiled transcriptome assembled from published short-read data from various tissues, with the remaining 69% being unique to NAc. These data provide a more complete picture of the NAc transcriptome than existing annotations and can serve as a comprehensive reference for future transcriptomic analyses of this important brain reward region.