Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq

Aguzzoli Heberle, Bernardo, Brandon, J Anthony, Page, Madeline L, Nations, Kayla A, Dikobe, Ketsile I, White, Brendan J, Gordon, Lacey A, Fox, Grant A, Wadsworth, Mark E, Doyle, Patricia H, Williams, Brittney A, Fox, Edward J, Shantaraman, Anantharaman, Ryten, Mina, Goodwin, Sara, Ghiban, Elena, Wappel, Robert, Mavruk-Eskipehlivan, Senem, Miller, Justin B, Seyfried, Nicholas T, Nelson, Peter T, Fryer, John D, Ebbert, Mark TW (May 2024) Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq. Nature Biotechnology. ISSN 1087-0156 (Public Dataset)

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DOI: 10.1038/s41587-024-02245-9


Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment. Here, as a step toward this goal for neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. We identified 1,917 medically relevant genes expressing multiple isoforms in the frontal cortex where 1,018 had multiple isoforms with different protein-coding sequences. Of these 1,018 genes, 57 are implicated in brain-related diseases including major depression, schizophrenia, Parkinson's disease and Alzheimer disease. Our study also uncovered 53 new RNA isoforms in medically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. We also reported on five mitochondrially encoded, spliced RNA isoforms. We found 99 differentially expressed RNA isoforms between cases with Alzheimer disease and controls.

Item Type: Paper
Subjects: Investigative techniques and equipment
Investigative techniques and equipment > assays
organs, tissues, organelles, cell types and functions
Investigative techniques and equipment > assays > RNA-seq
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL Cancer Center Program
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
CSHL labs > McCombie lab
CSHL labs > Goodwin lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 22 May 2024
Date Deposited: 28 May 2024 12:51
Last Modified: 28 May 2024 12:51
Related URLs:
Dataset ID:
  • https://
  • human-pangenomics/T2T/CHM13/assemblies/analysis_set/chm13v2.0.fa.gz
  • flair_filter_transcripts.gtf.gz

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