Very excited (enough to get up at 5am) about this Temporal Single Cell Analysis organized by @singlecellomics. First talk by the amazing Caroline Uhlers, recently snagged from MIT by @ETH_en#SCOGtempSC#SingleCell
Livetweets here. Apologies in advance to any sophisticated 'ML on scSeq/spatial' presenters whose work I misinterpret/misrepresent, still a novice to that field.
Very nice talk by Caroline. Two parts: 1) mapping RNAseq and images to the same latent space, to enable timecourse measurements (w images) of (inferred) RNA state. Seems like WIP but cool.
2) predicting cell responses. Her group tried to apply scGen (cool tool from @MohammadLotfol1) to the Broad CMAP but found it didn't work well. Turns out contractive elements of training set take over, unless you over-parameterize. Moderator @fabian_theis took this very well😄
@GioeleLaManno talks about (of course) #RNAVelocity. Brings up need for negative (randomized unspliced) control for latent space bias before applying to real data. Answering a lot of audience Qs about velocity. What does length of arrow mean in UMAPs? Does it work for #snucSeq?
More #RNAvelocity from @VolkerBergen. He's working on a model with dynamic learning with subpopulations rather than classic steady-state model. Seems to work better for cycling progenitors, and IDs genes likely contributing to velocity. Also nice cell fate collab w @dana_peer.
Now @dana_peer on about recent work by @SettyM, & work expanding on #RNAvelocity with CellRank: Markov modeling the propagation of velocities across #CellState manifold. This improves certainty about eventual fates when states overlap. Applying to lung cancer dedifferentiation.
Great job organizing and moderating @fabian_theis!
Nice inclusion of speaker breakout rooms with during coffee break. Closer to feeling like a live conference (Is a throng throng of human bodies or dozens of video tiles more overwhelming for speakers?🤔). Wetlab session up next.
Had to do some work and missed talked by Florian Erhard. Now @AlexandervanOu1 talks about ways to gain information about the distant past of RNAsequenced cells: Copy number variations (in tumor organoids), SNP-linked somatic mutations, lentivirus marking. Very cool ideas.
*Uhler not Uhlers
Final talk by Nikolaus Rajewsky, about metabolic labeling for timecourse data, looking at transcriptome in gene expression not latent space, and also about @LifeTimeIni. Latter is extremely cool and will be topic of another thread. Great job moderating & organizing @AE_Saliba.
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I'm struggling to wrap my head around the new Weissman lab myHSC depletion paper:
The first authors don't seem to be on twitter but hoping I can crowdsource a fun discussion. @dbgoodman @ImmunoFever @Jeff_Mold @Satpathology @CalebLareau...nature.com/articles/s4158…
The premise of the paper is that immune function declines with age in part because a haematopoetic stem cell (HSC) population skewed towards myeloid lineage increases in prevalence, and that targeting this population with antibodies can restore function. Cool idea!
❓1⃣: How well defined are myHSCs?
Here myHSC seems to be defined as CD150 high, based mainly on Beerman 2010 .
But looking at Figure 3, CD150 expression is a continuous distribution. Is this a clear cell population with somewhat understood behavior? pnas.org/doi/full/10.10…
If you want to build a career in biotech, should you get a PhD after college or join a company directly (as a Research Associate/RA, usually)?
There's no single answer, but I have the conversation often enough that I thought I'd share some pros/cons... (1/n)
First, see this thread about different types of biopharma companies. For reasons I'll get into, I think early stage (probably founder led) biotech is your best bet unless you still want to do PhD later.
(PS if you want to be a professor, it's 💯 PhD) 2/n
PhD will give you more options.
Some companies (incl. @GordianBio) will help you grow from RA to Scientist role (and beyond). But many, esp larger, companies have a glass ceiling if you don't have a PhD. Even if you pick one w/o glass ceiling, you'll be worse off it if fails. 3/n
All these points resonate, for early stage biotech at least. @erlichya touches on this, but I think worth separating "industry" into different clusters that will feel quite different to someone coming from academia (still oversimplified, of course):
Pharma (eg Pfizer) vs biotech:
You wear fewer hats, see less of the company but company as a whole spans wider range of expertise, fewer changes in direction, often higher income but no chance of getting rich. Both have job insecurity: pharma doesn't go die but programs do.
Clinical vs R&D stage biotech:
Clinical may still have R&D but it's no longer the biggest driver of success vs failure. Assay validation/rigor > assay development/invention. Clinical can feel more like pharma, but with more urgency/stakes: one program = life or death of co.
#SciTwitter After a lot of research and asking around, I'm making the lab equipment recommendations 🧵 I wish I'd had 2 months ago. RT/share with a #newPI or startup 🔬⚗️🛒
Note, much of the equipment hasn't arrived yet, will add comments after actual use.
-20 #freezer
Less clear, many viable options. We ended up getting a split of PHC MDF -30 (recommended as quieter) and much cheaper Corepoint Scientific/@VWR, will see which we prefer. Thermo hasn't failed #MBCbiolabs, but $$$ and several people said poor customer support.
As with all experiments, I expect that some of these will disappear and that others will be a central part of science in ten years.
But them happening at all is enough to renew a conversation about how science is funded and conducted.
🦸🏽 While I've been doing most of the tweeting, the Longevity Apprentices @LNuzhna@kush__sharma@edmarferreira & Tara Mei are the real heroes for running the operations.
This has been a great Apprenticeship project, merging action and exposure to research martinborchjensen.com/apprenticeship
🚅 The review + awards process was fairly smooth, thanks in part to @kush__sharma's custom reviewer UI. Several reviewers told us unprompted that it was their best review experience ever; the UI took 2 wks to make, so there's low hanging fruit for other agencies in that area.