Yupei You

Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain - Genome Biology Background Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or RNA isoforms made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Results Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profile the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in Human brain. We show most risk genes are more complex than previously reported, identifying 363 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity is detected in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirms translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in the brain. Conclusions Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in the human brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of candidate neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.

🧪Happy to share our latest paper in Genome Biology.

We profiled #RNA isoforms from 31 neuropsychiatric risk genes in the human brain using long-read sequencing. Unannotated isoforms commonly made up a significant proportion of a gene's expression.

genomebiology.biomedcentral.com/articles/10....

🔹 Access & reuse
The entire dataset is openly available for anyone developing tools or benchmarking long-read technologies.

🔹 What’s inside
• Bulk, single-cell & single-nucleus RNA-seq from 8 lung-cancer cell lines spanning 3 cancer types for realistic DE analysis
• Three long-read protocols (ONT PCR-cDNA, ONT direct RNA, PacBio Kinnex) and Illumina short-read sequencing
• Synthetic spike-in controls for ground truth

Benchmarking long-read RNA-sequencing technologies with LongBench: a cross-platform reference dataset profiling cancer cell lines with bulk and single-cell approaches Long-read RNA sequencing enables full-length transcript profiling and improved isoform resolution, but variable platforms and evolving chemistries demand careful benchmarking for reliable application....

Excited to share our latest preprint: LongBench—a cross-platform reference dataset profiling cancer cell lines with bulk and single-cell approaches.
www.biorxiv.org/content/10.1...

🔹 Why it matters
LongBench enables rigorous cross-platform comparisons of gene & isoform quantification, differential expression, alternative splicing, and allele-specific expression—helping the community evaluate and improve long-read methods.