More international collaborative work:
Single nucleotide variants in UNC13C associated with neurodevelopmental disorders affect ethanol sensitivity in Drosophila #raredisease #morbidgene #genetics #diseasemodelling www.sciencedirect.com/science/arti...

We started working on this in 2017 when I set-up my lab in Rotterdam. Many involved over the years, but I am particular grateful to both shared first-authors @ruizhideng.bsky.social (dry-lab) and Elena Perenthaler (wet-lab) and our collaborators (@eskeww.bsky.social , @roshchupkin.bsky.social)

Then we moved to the field of rare disease. Making use of the @genomicsengland.bsky.social 100,000 Genomes Project data, genomes from collaborators and from our genetics department @erasmusmc.bsky.social, we use BRAIN-MAGNET to filter for potential non-coding disease causing variants.

We then asked can we apply this model to interpret variants? We first tried on GWAS data 🧩:
BRAIN-MAGNET pinpointed which SNPs at disease loci actually affect enhancer function — correctly prioritizing previously experimentally validated variants for schizophrenia & depression.

Then came the AI. 🤖
We trained a convolutional neural network, BRAIN-MAGNET, directly on our experimental data.
It predicts enhancer activity from DNA sequence alone and highlights key nucleotides required for enhancer activity. Those predictions held up rigorous experimental validation

We then tested the activity of the same regions in embryonic stem cells, a developmentally earlier cell state. Comparing embryonic vs neural stem cells, we found “primed” enhancers: marked early in ESCs, activated later during neural differentiation. Capturing the early wiring of brain gene control

Ranking the functional enhancers according to their activity and linking them to their target genes provided insights into the regulatory grammar of gene regulation, for example showing enrichment of transcription factors at highly active non-coding regulatory elements (NCREs)

First, we used ChIP-STARR-seq to functionally test >148,000 candidate enhancers in human neural stem cells.
This represents one of the largest experimental atlas of quantitatively tested brain regulatory regions to date, providing novel insights in gene regulation during early brain development

Today, we presented at the meeting of the Dutch League against Epilepsy and EpilepsieNL, on some of our work on #ReNU syndrome, #SETD1B and #UGP2. Myrrhe Venema and Michela Maresca for their talks both won a Young Investigator Award for clinical and preclinical research, respectively. #proudPI !

New paper from us in Rotterdam:
"Long-read DNA and RNA sequencing reveal an intronic retrotransposon insertion in TCOF1 causing Treacher Collins syndrome"

www.sciencedirect.com/science/arti...

@hggadvances.bsky.social , Federico Ferraro, Tjakko van Ham, Marieke van Dooren and others #lrWGS

It took a while, but finally the Barakat lab is also on Bluesky! Come and follow us if you are interested in our research on genetic causes of neurodevelopmental disorders, the noncoding genome, functional genomics and much more happening in Rotterdam!