Sten Linnarsson
@slinnarsson
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Professor of Molecular Systems Biology at Karolinska Institutet. Backup Mastodon account: @slinnarsson @c .im
Joined June 2009
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Sweden is at 8000 new cases per day, and rising; 100+ deaths/day and rising; ICUs in Stockholm are at 101% capacity and rising; high schools are closed but shops, bars and restaurants are open (though not full) and face masks are still discouraged by the government. Wish us luck.
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Just like that, it’s out!
Scalable in situ single-cell profiling by electrophoretic capture of mRNA using EEL FISH
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Aviv Regev appointed new head of Genentech! Hard to think of a better person to lead Genentech - Aviv is one of the smartest people I know, a force of nature who gets things done and a visionary who sees farther than most.
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Hey scientific journals, please make sure every article on your web site has a prominent ”PDF” button. Make sure it leads to a PDF of the paper. Not a PDF embedded in a frame, not a proprietary format that’s not PDF, and not a PDF with a cover page. Just. The. PDF. Thanks.
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Proud to present our atlas of the developing mouse brain now out in Nature! Huge congratulations to first authors
@GioeleLaManno
@kimsiletti
, and all collaborators! 1/n
Free full text:
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Proud to present a comprehensive single-cell atlas of the developing mouse brain from E7 to E18, a total of 292,495 single-cell transcriptomes and 942 distinct clusters. A heroic effort led by
@GioeleLaManno
and
@kimsiletti
with Alessandro Furlan 1/n
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”To stop COVID-19, test everyone, repeatedly.” Me and Jussi Taipale propose a simple strategy to defeat coronavirus, and pose a challenge to the scientific community.
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Inspired by old maps of the earth, we made a figure in the style of an actual atlas, with isocurves for gestational time. We used the circumference to show a dendrogram of all clusters, and the corners to show additional information. 4/n.
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1/n I'm incredibly proud and excited that our paper "RNA Velocity of Single Cells" is out! This was such a fun and rewarding collaboration with
@KharchenkoLab
, and fantastic computational work by my student
@GioeleLaManno
! Thanks also to all collaborators.
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Our first stab at a complete-ish cell atlas of the adult human brain revealed thousands of cell types, organized on developmental principles. Plus a huge number of mysterious ”splatter neurons”. Tweetorial 🪡 below by the immensely talented
@kimsiletti
👇
So excited our single-cell transcriptomic survey of the adult human brain is on bioRxiv!
@slinnarsson
@MossiAlejandro
@ka_wai_rine
@ErnestArenasSWE
A really fun collaboration with Rebecca Hodge, Trygve Bakken, Ed Lein and others at the
@AllenInstitute
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Proud to see our spatial transcriptomic method, EEL FISH, out in bioRxiv! Many years in the making, based on
@LarsBorm
original idea with
@SimoneCodeluppi
as essential co-pilot. 1/n
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1/n Today we celebrate publication of our mouse nervous system atlas by scRNA-seq! Fabulous work by Amit Zeisel, Hannah Hochgerner and many collaborators.
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Underpowered, bullshit studies of human disease infuriate me. Why? Your underpowered study of distant galaxies will harm no-one, but your underpowered autism study will (1) divert future research in bogus directions (2) cause real autistic kids to be enrolled in bogus trials.
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An excellent and highly recommended improvement on algorithms for estimating RNA velocity of single cells! As usual from
@fabian_theis
lab with user-friendly software package, clear docs and tutorials.
Generalizing RNA velocity to transient cell states through dynamical modeling
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Oh, wow: ”GnRH replacement rescues cognition in Down syndrome | Science”
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(1/5) I’m very happy to announce that our preprint “Molecular Architecture of the Mouse Nervous System” was just released at bioRxiv! .
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Human brain atlas papers by
@kimsiletti
@MossiAlejandro
@ka_wai_rine
@ErnestArenasSWE
@EmelieBraun1
@MiriDanan
Rebecca Hodge Trygve Bakken Ed Lein
@LarsBorm
Elin Vinsland Erik Sundström and many others. With a stunning double cover illustration by
@IKapustova
In 21 papers across Science,
@ScienceAdvances
, and
@ScienceTM
, researchers with the
#BICCN
consortium present an atlas of the human and nonhuman primate brain in unprecedented detail.
The results uncover the genetic organization of the human brain.
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Massive opportunity alert! Start your new independent lab in any area of experimental or computational biomedicine, in our department at
@karolinskainst
. We offer a 1.1 M€ ($1.2M) startup package, amazing colleagues and a beautiful lab environment.
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In Sweden, childcare is virtually free ($75/month?), school is free, healthcare is free, college and university is free… and if this sounds good my department is hiring! Oh and we offer 13 MSEK to get you started!
🙏🏼 for some excellent replies about what we must do to fix this ⏬
Childcare is of course a major challenge (but not the only one..)
Do you have examples of institutions that really help w/ affordable, quality
#childcare
- on campus or in the community? Does yours?
Pls share!!
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FACS for fruit
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A few months ago, I got an email: ”Congratulation - Best Paper Award in Theoretical Computer and Information Sciences: Bioinformatics”. Supposedly for our paper ”RNA velocity of single cells” (with Peter Kharchenko
@KharchenkoLab
) 🧵
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Incredibly proud, and a bit nervous, to share the first major cancer paper from my group. For all the details, link to data, code and preprint, see thread below by
@MossiAlejandro
. Here, I will instead discuss one specific insight that was key in making sense of our data. (1/n)
Thrilled to share our work: Glioblastoma is spatially organized by neurodevelopmental programs and a glial-like wound healing response. Led by J. Janusauskas and myself.
.
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One year ago today, WHO declared SARS-CoV-2 a pandemic. By that time, Moderna and NIH had designed its virus candidate, completed GMP manufacturing, submitted an IND and obtained approval from the FDA. Just five days later, the first human was dosed in the phase I trial. 🤯👏
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So, today COVID testing was suspended in Stockholm because of a lack of capacity. The guy in charge says they couldn’t ramp up because of the several-month delivery time for new qPCR machines 🙄. It’s not like anyone could have predicted the need to ramp up testing…
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Det här är ju bara dumt. Dödligheten på 0.5-1% har varit uppenbar sedan i februari () och alla fattar att det betyder tiotusentals döda om smittan sprider sig i hela befolkningen. Precis därför har så många forskare varit kritiska till regeringens strategi
”När det gäller avlidna har vi kommit över 5.000 fall. En förskräckligt hög siffra jag tror ingen hade kunnat drömma om att vi skulle nå”, sade statsepidemiolog Anders Tegnell under torsdagens pressträff med svenska myndigheter.
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Publishers and editors: your periodic reminder to PLEASE place a button on the web page for every paper: Name the button ”PDF”. Make it go to the PDF of the paper. Not to your own fake PDF. Not the PDF in a frame. Not the PDF rendered using javascript. Just. The. PDF. Thank you.
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I just pushed Loompy 3.0 with many improvements to PyPi! Headline feature: one-liner to make a loom from fastq files in half an hour - uses the awesome kallisto from
@lpachter
to replace up to 24 hours of
@10xGenomics
cellranger (and velocyto)! Turorial:
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This. My iranian postdoc is not welcome to a meeting I’m co-organizing in Boston, due to the muslim ban. Had I known at the time, surely we wouldn’t have chosen the US venue. The US definitely is a terrible place for scientific meetings going forward. Sad!
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Current challenges in understanding the role of enhancers in disease | Nature Structural & Molecular Biology
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Just delivered a car full of personal protective equipment to Karolinska Hospital who were running out. Thanks all who helped & donated! Hospital was calm; few patients today. The problem seems to be on the supply side atm. Nurse said they run on just-in-time with zero stocks 😱
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You can make mice autistic by feeding them feces from autistic kids? Haha, right?! No, that’s an actual current Cell paper. And apparently neither the editors
@CellCellPress
nor reviewers bothered to even look at the plots.
O autism-is-caused-by-the-microbiome study!
How shall I nope thee?
Let me count the ways...
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Sadly the ship sailed long ago on the proper use of the word ”epigenetics”. Let’s just stop using it altogether. DNA modification, histone modification etc are perfectly clear and unambiguous. We’ll need a new term for ”heritable cell state” though. Maybe ”heritable cell state”?
Repeat after me. It's not _epitranscriptomics_, it's _RNA modifications_. Similar to the fact that its .. protein modifications not "epiproteomics". And our collective communication would be so much easier if we used DNA modification and histone modification not epigenetics
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”Cell types” are just the tips of the branching manifold from embryogenesis and tissue regeneration/homeostasis. In other words, if your tSNE has neatly separated clusters, it’s just because you’re missing all the ancestral cell states.
Really interesting to combine molecular and morphological readouts (how?) - but not sure that tSNEs would tell you much about cell types besides visualizing clusters (from higher dim analysis).
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After a year of questioning the use of face masks, clearly the swedish govt is finding it hard to convince people to now wear them on public transportation. I’m on the subway first time in months and estimate ~10% compliance.
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That we have not one but two vaccines in phase III already - six months in to the pandemic - is just amazing! The power of science.
Coronavirus vaccine tracker: How close are we to a vaccine?
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This is incredible work by Kenneth Harris at UCL! The whole brain participates in perception, decision and action. With a special role for the midbrain and the zona incerta(?!).
Recordings from 30,000 neurons in 42 brain regions of mice performing a visual discrimination task are reported in Nature. The findings reveal the spatial distribution of neuronal activity underlying vision, choice, action and behavioural engagement.
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This award recognizes the great joint work of
@GioeleLaManno
Ruslan Soldatov
@KharchenkoLab
@CramerLab
and many collaborators in developing RNA Velocity and . Also check out (
@fabian_theis
) and (
@lpachter
)
Congratulations to Sten Linnarsson (
@slinnarsson
) and his group - Laureates of the 2019
#Bioinformatics
Resource Innovation Award!
The award was given to the ressource
#Velocyto
: a new framework for the analysis of RNA velocity in
#SingleCell
#RNAseq
data.
#SIBAwards
#BC2basel
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Very sad to learn of the death of Paul Allen. He was a philantropist who made a real difference in science, funding basic research into brain function with a unique approach. His
@AllenInstitute
has made an outsized impact on neuroscience for which we all owe him our gratitude.
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An amazing trio of papers from Aviv Regev, Alex Schier, Allon Klein (x2!) and many colleagues. ”How one cell gives rise to an entire body” | Science | AAAS
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Aktuellt ikväll, om hur Island hanterat pandemin, gör mig så fruktansvärt sorgsen. De vet vad de gör och varför, har gjort allt rätt, och det funkar. Både (legendariske genetikern) Kari Stefanson och statsepidemiologen Gudnason är så uppenbart kompetenta.
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Single Cell Genomics 2019 is open for registration! Hurry - tickets are limited. Looking forward to welcoming you all in beautiful Stockholm archipelago this September! Don’t miss signing up for the boat ride to the venue through a thousand islands.
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Thread: In this new preprint with
@paulmromer
and Jussi Taipale, we show that population-scale testing and self-quarantine can stop the COVID-19 epidemic.
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Awesome osmFISH is out! Congrats to
@LarsBorm
@SimoneCodeluppi
et al.! ”Spatial organization of the somatosensory cortex revealed by osmFISH | Nature Methods”
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”RNA velocity fully solved”: scvelo from
@fabian_theis
group with
@VolkerBergen
and
@falexwolf
- my favorite kind of velocity!
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Sunrise over Stockholm after the longest night. 9 am and the sun wasn’t quite up yet. -8C and a thin layer of ice had formed overnight.
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We’re hiring! Seeking outstanding candidates to start their new labs at our department. All areas of fundamental biomedicine, but especially: Programmable medicines, Synthetic biology and Metabolomics. Generous startup packages. Apply here: (please RT)
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I think it’s extremely interesting that despite huge efforts to make pure cell TYPES in vitro, the cells still want to make TISSUES. We (
@GioeleLaManno
) saw same in ventral midbrain. Try to make dopaminergic neurons and you’ll get the whole ventral midbrain.
10/ Next, we focused on what ELSE is made alongside β-cells. When we differentiate, only ~30% of the cells become what we want: so what are the other 70%??? Thanks to scRNA-seq we can finally answer this question in as much detail as we want.
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”A large leap forward can be made if the immunotherapy target cells and pathways are characterized at high resolution before and after treatment, in clinical cohorts and model systems” Single-cell biology is about to eat drug development too!
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Big congratulations to
@GioeleLaManno
who defended his thesis today with John Marioni as opponent. I’m biased of course, but I think this must have been the best thesis in a long time
@karolinskainst
! Gioele now skipping postdoc, heading to EPFL as PI (says proud former mentor)!
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🙏paper is here:
Come and look at the best single-cell visualization so far. It is going to be difficult to beat it. By
@slinnarsson
at
@humancellatlas
#HCADevelopmentalNeuronsSessions
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I need your help. What are the best papers that show direct measurement of morphogen gradients, for example Wnt, Bmp, Shh or retinoic acid in the spinal cord? Direct measurement of the actual concentration gradients only, please. And please RT to get a wider audience. Thanks!
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I am shocked at the violence and barbary displayed today by Hamas and its followers. My thoughts are with all my scientist friends in Israel, at Weizmann, Technion and elsewhere. Be safe, be safe.
קהילת מכון ויצמן מתאחדת בצער עמוק על מותם של חפים מפשע ומייחלת להחלמתם של הפצועים ולשובם של השבויים, החטופים והנעדרים בשלום.
בשעה קשה זו, אנו מחזקים את תושבי כל ישראל, כוחות הביטחון וההצלה ומקווים לימים שקטים יותר.
שמרו על עצמכם ועצמכן.
In light of the recent events, the
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I have some experience
Anyone experienced in RNA velocity of scRNAseq data (trajectory analysis) at
@karolinskainst
?
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Eat two servings of salted peanuts per hour, live forever
A study in
@NatureFoodJnl
estimates the impact of certain food choices on a person’s health. For example, the health burden attributable to a serving of beef hotdog is 36 minutes of life lost, largely due to the detrimental effect of processed meat.
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If the button that says ”PDF” on the publisher’s site would go to the actual PDF. Not a frame around the PDF, not an ”enhanced” fake PDF, not a ReadCube or whatever your thing is called. Just. The. PDF.
Name one thing that would instantly revolutionize scientific publishing.
I’ll start:
PDFs that can handle embedded videos.
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On Dec 15 I said 100 people were dying of covid daily. Reply guys were incensed (liar! fear mongerer!). Due to reporting delays of over a month, accurate stats are only now in. Indeed, I was wrong (sorry!), we reached 100 only on the 16th. Since then, ICU admissions are up 40%.
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Haha no, because everyone is covered by the general welfare state (one year parental leave with 80% of full salary). Also, free health care, free university and pretty-much free daycare. Oh and unemplyoment insurance, dental care and retirement benefits.
Does your institution cover family health insurance benefits for trainees?
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Woke up to these ominous posters all over the apartment. If I go silent, now you know what happened. Please come and visit me in jail.
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Germany & Italy won’t be able to block banning Russia from Swift much longer. Let’s get it done, and allocate oil and gas reserves to those who need it most; e.g. balkans, Latvia, Bulgaria. The Germans made a bet on russian gas and lost, they should eat their loss in silence.
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A fantastic resource and great service to the community by
@vallens
! I use it all the time to find relevant papers and datasets.
Our database of scRNA-seq studies is now out in Database! -
I use this resource a lot to find datasets for tissues or diseases I want to investigate.
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Even if you have zero interest in Brexit or UK law (mine is non-zero, but not by much), David Allen Green is a joy to follow just because of his exquisite parsing of language. This here is a masterclass (for full effect read it in a Brummie accent).
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Raid on MSF hospital looks increasingly deliberate; a war crime that cannot go unpunished
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Cool Google data shows social distancing in real time: ”COVID-19 Community Mobility Reports”. Challenge: Find a country with less reduction in mobility than Sweden!
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Tick-tock, it’s RNA o’clock | Nature Methods
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”reviewer 2 is not persuaded that they represent a sufficient advance in our understanding of the mechanisms of genetic response to hypoxia to justify publication in Nature”
Professor Peter J Ratcliffe won the Nobel Prize this week for discovering the mechanisms that our cells use to detect and respond to low oxygen levels, known as 'hypoxia. This is a rejection letter he received when he submitted an article to
@nature
magazine. Don’t ever give up
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Up to three positions as Assistant Professor in Molecular Life Science at Karolinska Institute (SciLifeLab): 4+2 years, almost 2 M€ package - a great start for your career!
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Highly recommended software for RNA velocity! The differential kinetics test looks very powerful.
scVelo 0.2 is out ! Amongst others with
- new vignettes to facilitate interpretation of RNA velocities
- likelihood-ratio test for differential kinetics
- largely extended plotting functionality
with great contributions from S. Peidli, V. Marot & the GitHub community.
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Job opportunity: Help us develop drugs for brain cancer! We’re looking for an experienced staff scientist to develop and run advanced animal models of human brain cancer. Please RT.
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Big news -
@HansClevers
to head Roche early R&D (pRED)! After Aviv Regev took over research at Genentech (gRED) last year, are we seeing a trend here?
Entered my first academic lab in 1978. Fond memories of >40 years in science with great colleagues at public institutions in Kenya, the US and in my country, the Netherlands. Excited to step into the pharma world as head of research/early development at Roche, Basel in March
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@dana_peer
@arjunrajlab
We’re veering off Arjun’s topic here but just want to add that it’s very useful to plot the KNN on the tSNE or UMAP embedding (as edges between points). It reveals clearly when tSNE has got a cluster stuck behind another. We plot like this by default in my lab (not in papers)
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Starfish enterprise: finding RNA patterns in single cells
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Very happy to announce that we found a great home for our highly multiplexed RNA FISH method, EEL! Much more to come soon, from
@LarsBorm
and team. We look forward to working with
@rebusbio
to make EEL widely available. (COI: I’m now a paid scientific advisor for Rebus)
Rebus Bio Continues Expansion of Industry-leading Spatial Omics Platform with Breakthrough High-Plex Technology
#rebus
#spatialomics
#enhancedelectricfish
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MARS-seq, one of the original, great scRNA-seq methods, has been updated! Great hard work by
@HadasKerenShaul
@IdoAmitLab
! Cheap, index sorting, extremely few doublets…
MARS-seq2.0: an experimental and analytical pipeline for indexed sorting combined with single-cell RNA sequencing.
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Anders Björkman, DN Debatt 31/3 ”maximalt 1.000 dödsfall innan vi nått mer än 50 procent flockimmunitet” (), Björkman i Läkartidningen 28 april: 3000 döda vid flockimmunitet (); verklig siffra idag, 3175 döda
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Instead of a catalog of types, we should seek compact descriptions of the manifold going back to the zygote, in the spirit of
@fabian_theis
graph abstraction (and others like it). Even ignoring development, most cell types are dynamic, so rigid ”types” make little sense.
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After abrupt course correction in UK, Sweden is now alone in trying to achieve a controlled trajectory towards herd immunity. We’re riding an exponential tiger - wish us luck, we’re going to need it.
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Super-excited to see this project out, by
@GioeleLaManno
! All you need is a cryostat and any molecular method that works in tubes & now you have a highly resolved spatial omics method. We’ll soon see spatial versions of DNA sequencing, ChIP-seq, ATAC-seq and proteomics!
Excited to release the first preprint from my lab: a new framework to convert existing NGS tube-reactions into spatial techniques using compressed sensing principles and a probabilistic algorithm that we call
#Tomographer
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Having a research group is like having superpowers. Throw out an idea, two days later it’s solved! A quick request on Friday evening, two hours, done. I’m humbled by these powers. And grateful.
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SARS-CoV-2 biology is unravelling fast now: here’s both a mechanism of entry and a potential treatment, and we’re only two and a half months in!
New Article online now at Cell: SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
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Hot on the heels of our adult human cell atlas, we present the emergence of human brain cell types during the critical first trimester! Fabulous work led by
@EmelieBraun1
and
@MiriDanan
with many collaborators. Tweetorial 🧵below 👇🏼with links to preprint, data, and code.
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So, you’re a journal and you want me to review a paper? Pls just give me a link to quickly respond yes or no, or let me reply to the email directly. Don’t make me ”register” or ”reset password” every time. Play nice with password managers (looking at you, )
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Today our govt finally started to move on COVID-19. For the first time, social distancing is advised (but not mandated), and testing will be ramped up with a 1 bn SEK grant (€100 mn). Hope it isn’t too late!
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”Sweden shows what happens when you place too much trust in a handful of administrators, without first protecting yourself with a robustly argumentative culture that allows you to question whether they are right.”
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With Axon-seq, Eva Hedlund addresses a question I get all the time: are some mRNAs missed in scRNA-seq because they localize to axons (or dendrites)?
Our new paper is out: Axon-Seq Decodes the Motor Axon Transcriptome and Its Modulation in Response to ALS - E.H.
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Comprehensive single-cell transcriptome lineages of a proto-vertebrate: ”12-fold coverage for every cell at every stage of development”
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I opened an old radio to replace the fuse, and inside was a neatly folded piece of paper with the full schematics! That makes me very happy.
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Der Spiegel has the scoop on the slow EU vaccine rollout. Apparently due to screwup at the European Commission, possibly made worse by French lobbying for Sanofi (whose vaccine is anyway not due until Q4 2021!). This is a major scandal for EU.
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But it will be *very* important to have that autism paper retracted/rebutted before it does as much damage as the equally bogus vaccines-cause-autism papers.
@CellCellPress
editors have a grave responsibility and need to act quickly. Real kids with autism are at risk.
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BioNTech is on a roll
Researchers have designed an
#mRNA
vaccine that delayed the onset of and reduced the severity of multiple sclerosis-like disease in mice.
The vaccine restores the body’s tolerance to its own proteins, suppressing the disease's immune overreactivity. ($)
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I’ve played with scvelo for a while and it looks great!
Excited to share our scVelo manuscript - led by
@VolkerBergen
and
@falexwolf
, we generalize the beautiful RNA velocity concept from
@KharchenkoLab
and
@slinnarsson
to transient cell states through dynamical modeling. and
#scRNAseq
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I’m in Silicon Valley. I can order coffee with an app in my pocket supercomputer. But my US bank tells me it takes 7 days to make a payment to another bank. So I get to write a paper check instead, for the first time in my life. I’m feeling sooo 19th century modern!
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This is the proper way to count cells! It’s, like, actually counting each cell. Not much to argue with there.
Many work with microglia
How many microglia are there in the brain?
We found the answer with our most advance technology:
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This is why we always submit the preprint when we first submit the paper, and make all data available with the preprint. Science goes faster this way.
This is an amazing resource! It is important to note that the data have been available through for quite some time and have been very useful for many studies. I have used it quite a few times. The
@biorxivpreprint
preprint has been cited 22 times already.
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@ItaiYanai
I analyzed a
@CellCellPress
paper about ependymal cells and was surprised to find that the cells were actually endothelial. So the whole paper was basically completely bogus. It’s like reading a paper about cats but the authors failed to notice that the cats are actually salmon.
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RNA velocity in situ! Good stuff.
Check out our
@PNASNews
paper on 10K gene
#spatialtranscriptomics
by
#MERFISH
with ∼80% detection efficiency:
We infer
#RNAvelocity
in situ + pseudotime to reveal genes with
#cellcycle
dependent expression + more
#singlecell
#bioinformatics
#BigData
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