Matt Mulè

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!

Posit We’re happy to announce that we’re supporting Typst by funding one of their full-time engineers.

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

Parse Bio GigaLab and Vevo Therapeutics Tahoe-100 experiment 100 million cells assayed over 60,000 conditions and 1,200 drug treatments across 50 different tumor models

Parse Bio GigaLab and Vevo Therapeutics Tahoe-100 experiment open.substack.com/pub/albertvi...

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...

Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques Multi-modal datasets can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. We applied Markov fields to eliminate spurious correlations in a d...

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 !

Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation - PubMed We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (...

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.

Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus - Nature Medicine Simultaneous single-cell protein and transcriptome analysis identifies a baseline immune circuit associated with antibody responses to vaccination in healthy individuals and the severity of disease fl...

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...

Contrasting autoimmune and treatment effects reveals baseline set points of immune toxicity following checkpoint inhibitor treatment Immune checkpoint inhibitors (ICIs) have changed the cancer treatment landscape, but severe immune-related adverse events (irAEs) can be life-threatening or fatal and may prohibit patients from receiv...

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...

If we can identify a baseline immune state linked to later outcomes, we can risk-stratify patients and intervene earlier. For example, oncologists would benefit from knowing the likelihood of a patient developing immune-related adverse events (e.g. severe autoimmunity) after checkpoint inhibition.

Using the dsb method and mixed modeling/network analysis, we found that high responders to seasonal flu vaccines have a "Naturally Adjuvanted" baseline immune setpoint—mimicking the cell states specifically induced by an adjuvanted vaccine. doi.org/10.1016/j.im...

Utilizing population variation, vaccination, and systems biology to study human immunology - PubMed The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent invo...

With @tsanglab.bsky.social, I focused on advancing the concept of measuring homeostatic baseline immune system setpoints in humans. This framework was a cornerstone for how I thought about advancing precision medicine in immunology (far beyond vaccination alone). pubmed.ncbi.nlm.nih.gov/26187853/

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19 - Nature Immunology Smith and colleagues find that a multivariate signature of unresolved inflammation and altered iron homeostasis detected beyond 2 weeks following acute COVID-19 onset was the strongest early different...

I used dsb in Ken Smith's lab, where Aimee Hanson and I observed stress erythropoiesis and the multicell circuitry of inflammatory anemia in humans, which was related to long-term symptoms post-viral infection. www.nature.com/articles/s41...

GitHub - niaid/dsb: Normalize CITEseq Data Normalize CITEseq Data. Contribute to niaid/dsb development by creating an account on GitHub.

These experiments inspired our simple method for ADT denoising, dsb, which has been widely adopted and is available for R and Python github.com/niaid/dsb

Normalizing and denoising protein expression data from droplet-based single cell profiling - Nature Communications Current single cell protein expression profiling approaches come with substantial measurement noise. Here the authors discover the sources of this noise and develop a denoising algorithm that improves...

I trained with John Tsang & Ken Smith for my PhD at Cambridge w/ the Oxcam program. Early on, Andrew Martins & I uncovered significant noise in CITE-seq during optimization. This sparked a deep dive into experimental & computational noise deconvolution. www.nature.com/articles/s41...

Hello, world! We don’t routinely measure the immune system in the clinical laboratory. I’m working to make immune-based clinical tests a cornerstone of treatment selection, prognostication, and strategies to reprogram immunity across immune-mediated disease. Snapshot of my past work so far:

LTβR deficiency causes lymph node aplasia and impaired B cell differentiation Loss-of-function mutations in LTBR result in a stromal defect, leading to dysfunctional secondary lymphoid organs and combined immunodeficiency in humans.

New in #ScienceImmunology:

Research from @boztugk.bsky.social and team identifies an inborn error of #immunity caused by human LTβR deficiency, resulting in defective stromal cell signaling and impaired humoral immune responses.

Read more: www.science.org/doi/10.1126/...

Anyone knows a good set of validated T-cell epitopes? Meaning epitopes that definitely showed a good T-cell response.

I've used IEDB in the past but maybe there are other valuable resources?

#Immunosky

Curious about what a blood sample can reveal about humoral immunity? Our latest work combined sequencing methods and mass spectrometry to explore BCR and antibody repertoires and assess their synergistic potential. www.biorxiv.org/content/10.1...

I created a starter pack for systems immunology - let me know if you would like to be added. Excited to be here on
@bsky.app

go.bsky.app/PjH2Fuj