Jonathan Göke

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....

📢📢📢 The #AsiaRNA2025 abstract deadline has been extended to September 5th!!!

Join us at the inaugural Asia RNA Club Symposium 2025

🗓️ Nov 3-5, 2025
📍Seoul National University, Seoul, 🇰🇷

Register by Oct 10th

More info: asiarnaclub.org

#RNASky @rnasociety.bsky.social

🔄🙏🏽

@selfdz.bsky.social @archafox.bsky.social @fukayalab.bsky.social

The Asia RNA Club Symposium will be happening in Seoul in Nov 3-5, bringing together RNA scientists from the Asia-Pacific region. Excellent speakers and a great opportunity to connect! Abstract submission by Sept 5 asiarnaclub.org

Isoform-level profiling of m6A epitranscriptomic signatures in human brain Direct RNA-seq in brain reveals RNA isoform and region-specific m6A modifications, highlighting their role in gene regulation.

Our paper using Oxford #Nanopore direct RNA sequencing to identify m6A modifications on RNA isoforms in human brain is now out in Science Advances. 🧪
www.science.org/doi/10.1126/...

Narry Kim, Daniel MacArthur, Shi-Jie Chen, K Thangaraj, Ryan Lister, Karen Miga, Arnold Ou, Nikolaus Schultz, Leslie Beh, Koh Woon-Puay, Jingmei Li, PhD, Boxiang Liu, Jinyue Liu, Kristijan Ramadan, Patrick Tan, Yvonne Tay, Sunny Wong

🎉GIS turns 25! Join us in celebrating 25 years of innovation at #GIS25: Genome Innovation and Precision Medicine Conference, happening 11–12 September at Matrix, Biopolis, Singapore!

📅 Save the date and register now! Limited seats left!
👉 a-star.edu.sg/gis/news-eve...

#Genomics #PrecisionMedicine

I am not sure how to do Bluesky yet, but I want to tell the world about our neighborhood NMF method. First of many collaborations with the Pelka Lab!!

Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution - PubMed Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics and prognostics and for guiding th...

One of the gems from the last @genomeresearch.bsky.social #long-reads special issue, Part II.

Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resol… pubmed.ncbi.nlm.nih.gov/40086881/

Transcriptome-wide characterization of genetic perturbations Single cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these screens are often noisy due to cost and technical ...

New preprint from Ajay Nadig @nadigajay.bsky.social in Luke O'Connor's lab, with "a suite of statistical tools for formally modeling distributions of DE effects from RNA-seq experiments, including Perturb-seq"

www.biorxiv.org/content/10.1...

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

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

Learn more about the team led by @jonathangoeke.bsky.social and their work at:

www.a-star.edu.sg/gis/news-eve...

Join us at Genome Institute of Singapore! Great environment, stable funding!!

Excellent opportunity for PI positions at the Genome Institute of Singapore! Outstanding facilities, latest genomic technologies, strong and stable science funding. Junior candidates and established scientists are welcome to apply

Congratulations to @jonathangoeke.bsky.social, and our @astar-gis.bsky.social team on your SG-NEx project, providing a comprehensive resource that enables the development and benchmarking of computational methods for profiling complex transcriptional events at isoform-level resolution.

The first Singapore Long-Reads Symposium was a success! A massive thanks to the speakers: Keynote Heng Li, Ken Sung @jonathangoeke.bsky.social , @msikic.bsky.social & industrial partners @nanoporetech.com , @pacbio.bsky.social , @awscloud.bsky.social MGI_Technology Next Level Genomics & NovogeneAIT

An Analysis presents benchmarking results from the Singapore Nanopore Expression consortium project, plus a valuable resource of datasets generated from various long-read and short-read RNA sequencing technologies.
@jonathangoeke.bsky.social @astar-gis.bsky.social
www.nature.com/articles/s41...

Delighted to see this published. Congratulations Ying Chen and @jonathangoeke.bsky.social

Dr Heng Li presented his renowned work on the challenges and promises of long-read sequencing at GIS. His presentation on de novo assembly and variant calling created much excitement and discussion onsite and online. View the recording here👉 shorturl.at/EkDOC
Photo credit: @jonathangoeke.bsky.social

Looking forward to the Long-Read Symposium tomorrow! I will be talking about long read RNA-Seq and the SG-NEx Project github.com/GoekeLab/sg-...

RNA xkcd.com/3056

Hi everyone! This is an amazing opportunity to join an incredible team! Great environment and interesting research! If you’re looking for a great place to grow, check this out and come join us!😊

Paper out !!🥳big thanks to all authors @marliesoomen.bsky.social @diego-rt.bsky.social @kaessmannlab.bsky.social @jonathangoeke.bsky.social @lorenzamottes.bsky.social & 'bluesky-less'

Lots of interesting new TE (& genes) biology

Data fully browsable💻 👉 embryo.helmholtz-munich.de/shiny_embryo/

Great opportunity, great lab setting global standards in the field of long read RNA! Highly recommended if you’re at this stage in your career

We are recruiting! We have an open position for a postdoctoral fellow to join our team at the Genome Institute of Singapore to work with long read RNA-Seq data. It’s a beautiful city state and outstanding research environment! More details here: jglab.org/postdoc-posi...

Our new paper examining how to analyse longread RNA-seq with no reference genome. We compare approaches for assembly and downstream analysis, from transcript accuracy to differential expression. Lead by @alexyfyf.bsky.social. Thnx to all contributors incl. @qgouil.bsky.social for the pea data!

(reposted with correct URL)

GitHub - GoekeLab/bambu: Reference-guided transcript discovery and quantification for long read RNA-Seq data Reference-guided transcript discovery and quantification for long read RNA-Seq data - GitHub - GoekeLab/bambu: Reference-guided transcript discovery and quantification for long read RNA-Seq data

This work was down by Andre Sim, Min Hao Ling, Chen Ying, Sui Yue, together with Jay Shin's team at GIS. Let us know your comments and feedback, we aim to improve Bambu with every release! github.com/GoekeLab/bambu

GitHub - GoekeLab/bambu-singlecell-spatial: Transcript discovery and quantification for long read single cell and spatial transcriptomics data using Bambu Transcript discovery and quantification for long read single cell and spatial transcriptomics data using Bambu - GoekeLab/bambu-singlecell-spatial

The recommended way to run bambu-clump is through the nextflow pipeline (bambu-pipe), which optimises barcode detection, alignment, transcript discocery and quantification, and it also includes an option to identify fusion transcripts in single cells github.com/GoekeLab/bam...

...reads are only assigned to transcripts after similar cells are clustered into groups, reducing the noise in transcript expression estimates due to missing data. We also provide unique counts for single cells (and EM counts for genes/experiments with high sequencing depth)

The challenge with transcript expression estimation is the limited number of reads per gene, which makes the assignment of (non unique) reads to transcripts difficult. To address this, Bambu performs a clustered EM, in which ....