We're #hiring a computational #postdoc! PhD in computer science or other quantitative field? Join our mission: push the boundaries of precision #oncology with computational #epigenomics and #AI. https://t.co/OtKN34QnJT Please RT!

Looking forward to a great AACR Conference on Prostate Cancer in January!

Since circulating chromatin from blood is easy to sample, this approach opens a path to scalable discovery of chromatin QTLs across cell types and populations to dissect the genetics of common diseases. Grateful for the insights of @SashaGusevPosts and @LimingLiangHSPH!

Also, cancer reactivates developmental regulatory programs that can't be measured in differentiated tissues. cfcQTLs are highly enriched in developmentally restricted regulatory elements, revealing many cfcQTLs linked to disease that may act during development.

Circulating chromatin from patients with cancer turns out to be highly informative for discovering disease-associated cfcQTLs. Cancer cells shed chromatin into the blood, allowing capture of regulatory elements at GWAS risk loci that we can't sample from peripheral blood cells.

They linked 4,891 of these cfcQTLs to 1,011 traits and diseases (examples here).

To illuminate how these noncoding variants work, Ziwei and Surya analyzed cell-free ChIP-seq data from patients with cancer. They discovered >10,000 "cell-free chromatin QTLs" (cfcQTLs), where a genetic variant is associated with stronger activity of a regulatory element.

GWASs have linked many germline variants to genetically complex diseases like cancer. Many of these variants are in non-coding regulatory DNA and probably affect gene regulation, but it's hard to tell how they contribute to disease risk.

Fascinating study at the intersection of #liquidbiopsy and #genetics led by Ziwei Zhang and Surya Chhetri: https://t.co/ArOo6JS8HG. They found that circulating chromatin in blood can reveal how genetic variants contribute to disease by affecting gene regulation.

Much more in the preprint! Looking forward to translational applications to study cancer evolution and guide treatment selection. Grateful to @jberchuck, @manoliskellis, and our other collaborators who made this happen!

Why does this matter? These correlation patterns let us predict the activity of enhancers and the genes they regulate in cancer using cfDNA. E.g., we can detect activation of the AR enhancer, which drives resistance in prostate cancer, and HER2, a therapeutic target.

These complex patterns of correlation are explained by differences in nucleosome size and spacing at enhancers with high vs. low expression. These differences are caused at least in part by depletion of H1 linker histone protein near highly expressed enhancers.

The abundance of cfDNA fragments of certain sizes and distances from the enhancer TSS is tightly correlated/anti-correlated with enhancer RNA expression.

Excited to share our latest preprint by Alexis Yang and Gary Lee, in collab with the @jberchuck lab: https://t.co/cb3pRjketO. We found that transcription of enhancers (a mark of activation) causes distinct fragmentation patterns in #cfDNA.

Excited to share this molecular case report in @Nature_NPJ led by @KarlSemaan and @RashadNawfal. I expect to see more of this rare resistance mechanism with advances in AR-targeting therapy. Great colab with @Jberchuck, @DrChoueiri, and #MattFreedman. https://t.co/o71635XMy2

Great poster presentations at #AACR25 by @zezhangzzz and @marc_eid on computational methods for epigenomic liquid biopsy and circulating signatures of pancreatic cancer subtypes.

So excited for you, @KarlSemaan and thrilled you'll be staying in the neighborhood at @BrighamMedRes. It's a testament to the incredible hard work you've put in over the last two years in lab. Looking forward to collaborations to come!

So proud of mentees @RazaneHChehade, @KarlSemaan, @RashadNawfal, and @marc_eid for their fantastic talks at ASCO #GU25. Their translational projects should lead to better outcomes for patients with kidney or prostate cancer.

Great work, @RashadNawfal!

Thank you @DanaFarber_GU! Congrats to @JeremiahWala and @bill_lotter, and my deep gratitude to the Wong Family for helping us improve cancer care!

Beautiful work on profiling prostate cancer epigenomes from plasma to reveal clinical subtypes: https://t.co/ToKoyhs2Qy Congratulations, @researchwyatt, @TakedaDavid, and team! Still amazes me what a detailed view of gene regulation in cancer cfChIP-seq provides.