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Prikvačeni tweet
One of my PhD papers is published today
@eLife ! I’ll write a thread about this story later, but one funny bit I’ll share now is that I got a mini heart attack every time we got an email about the manuscript because of “rejection” in the title.https://elifesciences.org/articles/41090Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
Ron Gejman proslijedio/la je Tweet
Alright. Inspired by this tweet, I decided to read all relevant
#Coronavirus preprints (about 30 in all). Here's what I've found, a thread. 1/15https://twitter.com/ryneches/status/1223439143503482880 …
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We are inching towards autocracy.
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Ron Gejman proslijedio/la je Tweet
That’s the point, they are not drivers and our tissues are not cars: we’ve fallen victim to metaphor that obscures mechanism
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The discussion is beautiful: "The simplicity of the notion that cigarette smoking causes lung cancer through its mutagenic effects belies the underlying complexity of how tobacco shapes clonal dynamics, mutation acquisition and the selective environment in the bronchus"
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These findings continue to be astonishing. "In current smokers, at least 25% of cells carried driver mutations and 0–6% of cells had two or even three drivers." What is restraining these hopeful tumors?https://www.nature.com/articles/s41586-020-1961-1 …
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Ron Gejman proslijedio/la je Tweet
10 miles. Wow. Hard to believe how low NYC leaders can set the bar in 2020, but here we are. A *city* with the population and density of Brooklyn building only 10 miles of protected bike lanes per year is pathetic.https://twitter.com/andrewsiff4NY/status/1222539275436199945 …
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Listening to the
@nytimes@mikiebarb this morning interviewing@SenSchumer on impeachment drama when what do I hear? Schumer: "what did we used to learn in biology? Ontogeny recapitulates phylogeny." Barbaro: "Pardon?" Schumer: "I don't know.... forget it." Dying.Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
I don't want to get into the weeds about the model they propose. Instead, I just want to remind myself (and anyone reading) that the language we use to describe our experiments and the conceptual frameworks we use to interpret data can be as limiting as they are helpful. 12/n
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The authors of the "criterion of immunogenicity" article propose a completely different conceptual framework for immunogenicity that is based on discontinuities in the normal pattern of antigens encountered by the immune system. 11/n
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I freely admit to at times focusing far more attention on the narrow, tractable question of which mutations lead to immunogenic epitopes than on the broader question of what makes a cell immunogenic overall. 10/n
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The MHC bound peptides are just a few shapes on the surface of the cell. In pursuit of simplicity, we have ignored the broader question of what makes a tumor recognizable to the immune system: which is a function of the hundreds to thousands of alterations in cancer cells. 9/n
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Isn't there a little bit of hubris in believing that we can explain outcomes in oncology on the basis of this small set of differences compared to the massive number of total differences between a cancer cell and a non-cancer cell? 8/n
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But what we are also doing is relying on the crutch of "self" vs "non-self." Indeed, a short wild type ("self") peptide vs. a short mutated ("non-self") peptide is about the simplest example of self vs. non-self you can find. 7/n
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Partially we do this because we have reasonably good computational tools to predict whether peptides will bind to an MHC molecule and reasonably reliable assays to test immunogenicity. 6/n
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An example: In the field of T cell immunogenicity in cancer we have focused tremendous effort on characterizing MHC bound neoantigens which differ from their wild-type counterparts by only a single amino acid. 5/n
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We still use the self/non-self language even though it is no longer factually correct and is even more conceptually wrong. Why do we do this? Perhaps because the idea of self/non-self is seductively simple. 4/n
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Specifically, they point out that it's not the *endogenous* vs *exogenous* origin of an antigen that is critical, but rather the *shape* of the antigen that matters. But wait, isn't this obvious (in 2020)? Yes! It is... and yet 3/npic.twitter.com/4mXjI2qTrR
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wherein they criticize the self/non-self paradigm (and language) of immunology.pic.twitter.com/SIcDqxXlBz
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Interestingly, one of the examples was in clarifying the concept of immunogenicity and referenced this beautiful article by
@pradeu and Carosella that was new to me https://www.pnas.org/content/103/47/17858?ijkey=1116e668dcb13921f941348643c7e24848458b72&keytype2=tf_ipsecsha … "On the definition of a criterion of immunogenicity" 2/nPrikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi
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