I officially started my postdoc in @BeEngelhardt 's lab at @GladstoneInst last month!! I’m working with some phenomenal collaborators to improve cancer immunotherapy using genomic and spatiotemporal data. Excited to meet those at the @UCSF Mission Bay and @Stanford campuses!

Lastly, I’m grateful to NIH for funding this project through my F31 fellowship, to editor Dr. Nele Hug, and to all reviewers. Hope you all enjoy the paper! end/.

Thanks to all my co-authors including @marcjwills_, Hongyu Shi, @ivazquezgarcia, @GreedyApple, @SohrabShah, Andrew McPherson, and the rest of the Shah Lab. I learned so much from all of you along the way. 10/.

These results tell us that cell cycle fractions alone don’t approximate clone fitness/prolif rates in genomically unstable (high CIN) tumors. This limitation is likely due to different levels of replication stress and cell death between clones. Negative selection matters!! 9/.

The lack of correlation between SPE and expansion was most extreme in whole genome doubled (WGD) clones which were significantly depleted of S-phase cells relative to diploid clones despite having higher fitness. We found evidence of this both in vitro and in vivo. 8/

Our data showed that while SPE positively correlated with expansion between TP53 WT clones and doubling time between different gastric cancer cell lines, SPE didn’t correlate with expansion in TP53-/- mammary epithelial cell line or TNBC clones. 7/

The second new piece of the paper was our investigation into which contexts we could “predict” the expansion (i.e. proliferative fitness) of a given clone using its S-phase enrichment (SPE). We leveraged cell lines and PDXs with time-series scWGS data to answer this question. 6/

Interestingly, there were some tumor Xp arms with earlier RT than we expected based on their 1:1 ratio of A:B alleles. Turns out these Xp arm B alleles were “reactivated” after loss of the Xq arm B allele which contained the XIST locus responsible for in cis inactivation. 5/

Given that inferred RT allowed us to phase the inactive chrX allele onto A/B haplotype labels, we recurrently found more Xa than Xi alleles in our cohort of TNBC and HGSOC tumors. 4/

While most of the paper is similar to the preprint (thread here . I want to draw attention to two new results in Figs 5 & 6 that matured during the peer review process. 3/.

PERT directly infers copy number, replication timing, GC bias params from each scWGS sample read matrix. This makes PERT robust to biological (CNA or RT) and technical (GC) batch effects when classifying S-phase cells unlike pretrained models which can’t account for variation. 2/

Happy to announce that PERT is now published in @NatureComms ! With PERT, we explore replication timing variability (Fig 3-4), chrXi reactivation (Fig 5), and how S-phase fractions struggle to approximate clone fitness (Fig 6). 1/n.

RT @marcjwills_: We posted a couple of preprints recently, quick summary below 👇.

RT @MaryamPourm: Very excited to share our article detailing spatial features of Epstein-Barr virus positive and negative classic Hodgkin l….

Come for the linear time OT, stay for the interpolation bw lamp & toilet. Great work Doron!.

I’m happy to announce that I will be defending my PhD thesis two weeks from now! My defense will be a tour of all my favorite bits of research over the past 4.5 years, spanning both ML algorithm development and single-cell analysis. Register below:.

RT @minsoo_kim1: Thrilled to announce that my PhD thesis work has been published in Nature Genetics! 🎉 Huge thanks to my advisors, @SohrabS….

This is one of the better reviews I've read. We have to think about both formation rates and fitness impacts to understand how complex events contribute to tumorigenesis, mets, drug resistance, etc. Worth the read even if you've been thinking about these problems for a while.

RT @MildredUnti: So excited to announce that my most recent work has been published. If you’re interested in genetically encoding circular….

RT @mmdarmofal: Treatment options are limited for the 3-5% of patients who have cancers of unknown primary. So, we are excited to present 💥….