Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms

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., , , # Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms

[https://doi.org/10.5061/dryad.0rxwdbs68](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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