Here is the output in case there are issues with the link.

Prompt: Do research. find peer-reviewed publications of pyrrole-imidazole polyamides used to activate gene expression (transcriptional activators). Expected output: an exhaustive list of references to the original publication.

The LLM (AMIE in this case) performs higher (59.1% top-10 accuracy) than the clinician with the LLM (51.7%).

Another study consistent with what @emollick.bsky.social has been sharing for a while now.

www.nature.com/articles/s41...

What a fantastic day at Tufts University! Sergei Mirkin, Catherine Freudenreich, and @sarahhengel.bsky.social. What a special place.

They arrive at a model where ecDNAs can alter the cell in three profound ways:
1. Amplify oncogenes through high copy number
2. Create new chimeric circles combining different regions of the genome
3. Disrupt normal gene expression when they reintegrate into chromosomes

What happens upon integration? The impact ripples beyond the insertion site - genes within 2 Mb of where the ecDNA lands show altered expression.

ecDNAs were almost surely the source of these rearrangements. The evidence: DNA sequence variants (SNPs) found on the ecDNA were present in the integration sites! 🔍

The really cool part? Visualization of rearrangements with circos plots showed these tree-like patterns, where DNA from chromosome 2 (containing MYCN) acted like a trunk, with branches reaching out to multiple chromosomes. Most of these represented re-integrations of ecDNAs.

There's MYCN, no surprise! But in addition, they identify several other genes on ecDNAs.

They find both eccDNA and ecDNA present in these neuroblastoma tumors. I'll focus mostly on their ecDNA results here. The ecDNAs are large and carry full genes.

What is Circle-seq? The method enriches for circular DNA using magnetic beads, removes linear DNA with exonuclease treatment, and amplifies remaining circles using φ29 polymerase. protocolexchange.researchsquare.com/article/npro...

The first oncogene pinpointed to these ecDNAs was MYCN - a major cancer driver gene in neuroblastoma. This discovery in 1983 (by a young Fred Alt!) opened up a new way of thinking about how cancers can amplify important genes. 🧬
www.cell.com/cell/abstrac...

First, some history: In 1965, scientists first observed small DNA molecules outside chromosomes in neuroblastoma cells. They called them "double minutes" because they often appeared in pairs under the microscope. 🔬
www.sciencedirect.com/science/arti...

For my first post here at 🦋, let me tell you about a lovely paper by Richard Koche, @anton-henssen.bsky.social, and colleagues that covers how extrachromosomal DNA (ecDNA) drives cancer genome remodeling in neuroblastoma. It's a great story about cancer biology and genome organization! 🧬