I essentially took the entirety of the first 2.5 years of my PhD, 55 hours/week and set them on fire. Nothing productive or useful arose.
Those years are also the years that made me a very good scientist.
Grunt work and failure and friction IS the work. There is no way around learning.
“I shall send off the manuscript today or Monday. It is an extremely poor affair; I must say something & have nothing worth saying. Lock it up carefully, I hate it to that extent it would break my heart to write it again.”
Charles Darwin captures the joy of academia in a letter to his daughter, 1871
Nature Genetics: The polygenic, omnigenic and stratagenic models of complex disease risk www.nature.com/articles/s41... 🧬💻🧪 read free: rdcu.be/eZ2AE
The central limit theorem is a mathematical truth so powerful that it often strikes newcomers as impossible, like a magic trick of nature. Through it, the most random chaos can lead to striking predictability.
Today in @nature.com, we describe how discarded reads in biobank-scale WGS can help resolve the genetic predictors and consequences of Epstein-Barr Virus (EBV) infection.
Wonderful working with @ryandhindsa.bsky.social @sherrynyeo.bsky.social @erinmayc.bsky.social
www.nature.com/articles/s41...
More interesting findings from the Casanova group on IFN neutralizing antibodies
1/ We are excited to share our new report in PNAS: all three cases of encephalitis triggered by the live-attenuated chikungunya (CHIKV) vaccine (IXCHIQ®) are due to pre-existing autoantibodies neutralizing type I IFN (AAN-I-IFN) (doi.org/10.1073/pnas...).
Great story from the Nieswandt lab in Science: uncovering a non-classical platelet mechanism that drives inflammation via integrin- and tetraspanin-rich tethers. A fresh angle on thrombo-inflammation. Happy to be part of this work!
www.science.org/doi/10.1126/...
PCA is one of those techniques that sounds unreasonable (yeah sure we all want to fit a p-dimensional ellipsoid to our data) but turns out to be a reasonable solution to a wide range of problems.
Also: I do hope stackexchange has been archived, because it is my gen's library of alexandria
Can confirm.
Dear single-cell bluesky community: We’re running Cell Ranger (5’ scRNA-seq) on sorted human CD8+ T cells with a custom library. Custom seqs (27–133 bp) appear in FASTQs + BAM but aren’t mapped. They are filtered out by STAR for being too short—any way to lower the length limit or workaround?
You may be able to make them “feature barcodes” like an ADT library by putting them into a csv and referencing that with -feature_ref and running the CITE-seq workflow. That would bypass star but would require the custom library has the same structure as the ADT with barcode and UMI in R1.
An image of a wiring diagram showing a 2-line to 4-line decoder
Which output is on when both switches are open? And can you guess why ChatGPT's 03 reinforcement learning model got this wrong initially? #reinforcementlearning #ai
"We are speaking on behalf of hundreds of NIH staff who are standing up together to say: WE DISSENT.
I am so scared about doing this but I am trying to be brave for my kids because it's only gonna get harder to speak up."
Thank you to Dr. Jenna Norton and NIH scientists for your courage!
At Posit, we love @typst.app:
⚡ Make PDFs in milliseconds, not minutes
✨ The power of LaTeX with today's technologies
✍️ Modern typography (including emojis!)
🧠 Clear mental model
So I'm thrilled to announce that we're now supporting its development: posit.co/blog/posit-a...
#rstats
I've been developing a semantic search tool that covers not just bioRxiv and medRxiv, but the entire PubMed database. This means you can search across a massive collection of biomedical research using keywords, questions, hypotheses, or even full abstracts. Try it out: mssearch.xyz
scRepertoire 2: Enhanced and Efficient Toolkit for Single-Cell Immune Profiling
www.biorxiv.org/content/10.1...
The measles vaccine is given as a shot but it is surprisingly good at inducing protective immunity in the respiratory tract (mucosal IgA). Our new study provides some clues about why...a thread (1/8) #IDSky #MedSky #lungs #immunology #ImmunoSky academic.oup.com/jid/advance-...
Graphical summary of our paper. In mice, prior lower airway exposure to diverse inflammatory stimuli, including chronic bacterial infections such as M. tuberculosis, acute bacterial infections such as pulmonary S. aureus, viral infections such as Influenza A, type-II allergic responses such as the OVA-Alum model, activation of pulmonary TLR9 by CpG or pulmonary TLR1/2 by Pam3CSK4 leads to reduced viral burden upon subsequent infection with SARS-CoV-2 (SCV2). (2) This SCV2 restriction occurs prior to induction of SCV2-specific adaptive immune responses and is mediated through innate immune responses, including the induction of IFN-I, TNFα and IL-1 and sustained changes to the TRM (Tissue resident macrophage) cellular compartment and the pulmonary epithelium. (3) Innate cytokine and TLR signaling to both recruited immune cells and the pulmonary epithelium creates a microenvironment in the lung that limits early replication of SCV2. IFN-I signaling to pulmonary ECs (epithelial cells) increases expression of interferon-stimulated genes, that likely cell-intrinsically limit viral replication. TNF- or IL-1 suppress SCV2 independently of IFN-I signaling. TNF acts exclusively through radio-resistant cell types such as the lung epithelium, whereas IL-1 affords control both direct and indirectly, through either stromal and hematopoietic cell types, to restrict overall early SCV2 burden.
Best #Nikolaus 🎅! Our paper on how the 🫁 microenvironment can shape #innate immunity against #viruses is out @sciimmunology.bsky.social This was a herculean effort brilliantly led by @pauljbaker.bsky.social who singlehandedly established the model in the lab during the pandemic. 🧪 #Immunosky 1/9
would love to be added!
Re-pinging for new arrivals: here's a starter pack of researchers who work on variable immune receptors: let's all have nice repertoire chats together.
go.bsky.app/Gi2dcGd
Prioritized mass spec data acquisition increases proteomic data completeness & coverage depth.
The increase is largest for the most challenging proteins.
When using TMTpro, data completeness reaches 93% for all proteins across multiple sets.
nature.com/articles/s41...
Amazing starter pack, would love to join the list!
New de-novo TCR design preprint from @dkarthikey1.bsky.social just dropped:
TCR-TRANSLATE: Conditional Generation of Real Antigen Specific T-cell Receptor Sequences
www.biorxiv.org/content/10.1...
Nice paper using an inverse covariance / partial correlation network analysis with graphical Lasso to identify direct associations with an outcome variable.
Hoping to engage with everyone on here to discuss science. Reach out for collaboration. If you made it this far, PDFs of everything and links to open source software are on this website mattpm.net !
Prior to all this I focused on clinical diagnostics with @drchrishourigan.bsky.social pubmed.ncbi.nlm.nih.gov/27544285/. I'm returning to the clinical lab for residency training where I aim to develop clinical tools to prognosticate, treat and reprogram immune system subtypes across diseases.
This pairs well conceptually w/ our earlier work showing how the same temporally stable immune setpoint correlates with later plasmablast activity with differing context-dependent outcomes:
- productive vaccine response in healthy people
-disease flares in SLE patients
www.nature.com/articles/s41...
With Chen Zhao, Arun Rajan, & colleagues at NCI, we identified a stable immune setpoint featuring TEMRA cells, metabolic rewiring, and elevated resting inflammatory tone in DCs—all linked to myositis following anti PD-L1. (updates soon)
www.biorxiv.org/content/10.1...
jitc.bmj.com/content/9/Su...
