Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms
Data files
Mar 13, 2024 version files 139.79 MB
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DataS1.tar.gz
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DataS2.xlsx.zip
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DataS3.tar.gz
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README.md
Abstract
RNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders, yet the role of cell-type-specific splicing or transcript-isoform diversity during human brain development has not been systematically investigated. Here, we leveraged single-molecule long-read sequencing to deeply profile the full-length transcriptome of the germinal zone (GZ) and cortical plate (CP) regions of the developing human neocortex at tissue and single-cell resolution. We identified 214,516 unique isoforms, of which 72.6% are novel (unannotated in Gencode-v33), and uncovered a substantial contribution of transcript-isoform diversity, regulated by RNA binding proteins, in defining cellular identity in the developing neocortex. We leveraged this comprehensive isoform-centric gene annotation to re-prioritize thousands of rare de novo risk variants and elucidate genetic risk mechanisms for neuropsychiatric disorders.
README: Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms
https://doi.org/10.5061/dryad.0rxwdbs68
Description of the data and file structure
Data S1: This dataset contains transcriptome annotations in General Transfer Format (gtf) generated by long-read sequencing of bulk tissue samples in this study. The annotations delineate genomic coordinates, exonic/intronic boundaries, and salient attributes for each detected transcript isoform.
Data S2: Full-length transcriptome of the developing human brain. (A) Transcript classification using the TALON pipeline; (B) Transcript quantification using the TALON pipeline; (C) Filtering criteria used to generate the TALON whitelist.
Data S3: This dataset contains transcriptome annotations in General Transfer Format (gtf) generated by long-read sequencing of single cells from the human neocortex.
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