A brief summary of our recent paper:
"Five mutational “fingerprints” could help predict how visible tumours are to the immune system"
eurekalert.org/news-release...
Link to our paper:
link.springer.com/article/10.1...
#Cancer #CancerResearch #Science
9/ Takeaway: Protein-level mutation patterns provide a complementary lens to DNA mutational signatures—linking mutagenesis + repair defects to peptide properties, immune contexture, and therapy response.
8/ But there’s nuance inside AAS4:
Among AAS4-driven tumors, specific HLA variants are enriched in immune-hot cases.
So antigen presentation genetics may modulate whether an AAS4 tumor ends up “cold” vs “hot.”
7/ One signature stood out clinically: AAS4.
AAS4 is associated with predominantly immune-cold tumors, poor prognosis, and limited response to immune checkpoint blockade.
6/ That biophysical bias matters for immunology.
By shaping the properties of mutated peptides, AASs can influence neopeptide immunogenicity → and, downstream, the tumor immune microenvironment.
5/ Next: not all amino acid substitutions are equal.
Different AASs preferentially generate amino acids with distinct biophysical properties (think charge, polarity, size).
4/ Why does that matter?
Because it suggests the protein-level consequence can converge even when the DNA-level cause differs.
3/ Importantly, these AASs aren’t a 1:1 readout of any single DNA mutational process.
The same AAS can be produced by multiple, largely unrelated exogenous + endogenous mutagenic processes.
2/ ~82% of tumor samples are dominated by a single AAS.
So despite massive heterogeneity, most cancers have one main “protein-mutation style.”
1/ Cancer mutations look chaotic—different tumors, different genes, different DNA changes.
But at the protein level, we found surprising order.
Introducing amino acid substitution signatures (AASs): 5 recurrent patterns that repeatedly show up across cancers.
Our new paper is out:
Five dominant amino acid substitution signatures shape tumour immunity
link.springer.com/article/10.1...
Thread 🧵⬇
#cancer #tumor #immunity #immunotherapy #oncology
C > U mutations generate immunogenic peptides in SARS-CoV-2
APOBEC enzymes—key players of the innate immune system—induce mutations that become fixed in viral genomes and enhance immune recognition.
nature.com/articles/s41...
#COVID_19 #Immunology #virus #infectiousdiseases #vaccine #Genetics
C > U mutations generate immunogenic peptides in SARS-CoV-2 @natcomms.nature.com @matemanc.bsky.social
@csabapallab.bsky.social
www.nature.com/articles/s41...
I C U mutant!
Our new paper is out! Our immune system doesn’t just fight viruses – it edits them.
APOBEC enzymes introduce C>U mutations that often make viral proteins easier for HLA molecules and T-cells to detect, boosting immune recognition.
nature.com/articles/s41...
#COVID_19
I C U mutant!
Our new paper is out! Our immune system doesn’t just fight viruses – it edits them.
APOBEC enzymes introduce C>U mutations that often make viral proteins easier for HLA molecules and T-cells to detect, boosting immune recognition.
nature.com/articles/s41...
#COVID_19
www.pnas.org/doi/10.1073/...
How cancer arises: Genetics releases, plasticity creates, genetics stabilizes
