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Prikvačeni tweet
Really excited to share the first chapter of my PhD on how genome-wide linkage in cancer reduces the efficacy of selection via Hill-Robertson interference (HRI), with mentors
@cd_mcfarland,@PetrovADmitri and@cncurtis. https://bit.ly/2lTDQnT (1/10)Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
Susanne Tilk proslijedio/la je Tweet
Ever wonder which tumor suppressor alterations impact drug responses in vivo? Check out our recent work on using improved Tuba-seq to quantify genotype-specific treatment responses in lung cancer.https://www.biorxiv.org/content/10.1101/2020.01.28.923912v1 …
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Susanne Tilk proslijedio/la je Tweet
Check out the paper on G3 by the amazing
@SusanneTilk &@sharGblum and coauthors. https://www.g3journal.org/content/9/12/4159 … 1/nPrikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
Susanne Tilk proslijedio/la je Tweet
My first study on somatic mutations in corals! We found heterogeneity among different branches of individual corals. This occurs at a similar frequency as has been reported in humans. Intriguingly, for corals the most common form of that heterogeneity is losses of heterozygosity.https://twitter.com/OfficialSMBE/status/1194647995876139008 …
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Susanne Tilk proslijedio/la je Tweet
I am extremely excited about this work on the way natural selection succeeds and crucially fails to weed out deleterious mutations in cancer due to the constraints posed by linkage and Hill-Robertson interference. https://www.biorxiv.org/content/10.1101/764340v2 … 1/n
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How successful tumors overcome this deleterious load is an exciting, open question. Similar to constraints in germ-line evolution, we think that preventing protein mis-folding is an important first step. We’d love to hear what you think! (10/10)
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Thus, this allowed us to estimate that in elevated mutational burden tumors (>95% of cancers), deleterious passengers accumulate and confer an individually-weak, but collectively-substantial fitness cost of ~40% that impacts tumor progression. (9/10)
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Finally, we demonstrate that a simple evolutionary model incorporating HRI can explain these observed patterns of selection and allowed us to estimate the mean fitness effects of passengers (~1%) and drivers (~18%) – much larger than previously estimated. (8/10)
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Importantly, we see that attenuated selection on CNAs and SNVs is generic to tumor evolution. This pattern persists across broad and specific tumor sub-type categories. (7/10)pic.twitter.com/bKJ8vSbQUV
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We see the same trend in somatic CNAs. Using a dN/dS-style statistic called dE/dI (fractional overlap of CNAs in [E]xonic versus [I]ntergenic/[I]ntronic regions) – we similarly see that selection on CNAs attenuates as the mutational burden increases. (6/10)pic.twitter.com/LUg6hlRJFk
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To test this idea, we calculated dN/dS in tumors stratified by their mutational burden and observe that negative and positive selection attenuates as more mutations accumulate in tumors. (5/10)pic.twitter.com/WF1WIJ02mV
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Since linkage effects get stronger as mutation rates increase, tumors with elevated mutational burdens should be particularly inefficient at removing deleterious passengers due to genetic hitchhiking and Muller’s Ratchet. (4/10)pic.twitter.com/vVW4z6C6q1
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We hypothesized that since tumors evolve asexually, under the constraints of genome-wide linkage, mutations are unable to be removed by negative selection (or favored by positive selection). (3/10)
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Here, we try to resolve why signals of negative selection are largely absent in cancer, yet pre-dominant in the human germ-line. (2/10)
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Susanne Tilk proslijedio/la je Tweet
Today at petrov lab meeting we explored a very important question...which spicy Cheeto is spicier? We double blinded and controlled for Cheeto size but we’re still really confused about whos spicier.
@ChesterCheetah, can you help us out?pic.twitter.com/gflnUsHAu7
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Susanne Tilk proslijedio/la je Tweet
Excited to share our new paper
@NatureComms on clonal replacement and heterogeneity through neoadjuvant therapy in Her2+ breast cancer: https://rdcu.be/blOEK . Great work from@caswell_jin and Katherine McNamara and the rest of the team!Hvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
Susanne Tilk proslijedio/la je Tweet
We have a new paper on bioRxiv today. It’s not a paper I was planning to write during my first semester as a postdoc. https://www.biorxiv.org/content/early/2018/12/13/495275 … (1/n)
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Susanne Tilk proslijedio/la je Tweet
The Geiler-Samerotte lab is recruiting graduate students and postdocs! Graduate students apply here by December 1rst: https://sols.asu.edu/degrees/grad/evolutionary-biology-phd … Postdocs apply here: https://postdocjobs.com/posting/7054334 pic.twitter.com/9dO9UKWNOF
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Susanne Tilk proslijedio/la je Tweet
COLBERT (control of lineages by barcode enabled recombinant transcription) for cancer research!
#sacb2018@colbertlateshow@AmyBrock_PhD http://sacbmeeting.org pic.twitter.com/jnb8qpY3hJ
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Susanne Tilk proslijedio/la je Tweet
Christopher McFarland of
@Stanford talks about using TuBa-Seq + CRISPR/Cas9 + modeling to study genetic drivers of lung cancer evolution#SACB2018pic.twitter.com/T9887Pd8Am
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