Jonathan Göke

@jonathangoeke.bsky.social

Senior Group Leader and Assistant Director, Genome Institute of Singapore, A*STAR. We develop computational methods for long read RNA-Seq. Follow the team @goekelab.bsky.social https://github.com/goekelab

🧪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....

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.

genomebiology.biomedcentral.com

Scientists at A*STAR GIS have unveiled SG-NEx, one of the world's largest long-read RNA sequencing datasets! 🌍🔬 With 750M long RNA reads, it enhances detection of complex RNA features, aiding disease research and precision medicine. Available via AWS Open Data Registry. #Genomics #PrecisionMedicine

SINGAPORE SCIENTISTS UNVEIL ONE OF WORLD’S LARGEST LONG-READ RNA SEQUENCING DATASETS TO ADVANCE DISEASE RESEARCH

a-star.edu.sg