Artem Mikelov

Somatic mutation and selection at population scale - Nature A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Our latest work is out in Nature today. In this paper, we introduce an improved version of NanoSeq, a duplex sequencing protocol with <5 errors per billion bp in single DNA molecules, and use it to study the somatic mutation landscape of oral epithelium in >1000 people www.nature.com/articles/s41...

I wonder if it is true for humans as well - the work shows it in a very particular mouse model in a very particular immunization setting (and lacks Methods section at this stage).

The term 'affinity maturation' understates the influence of somatic hypermutation Three recent papers quantify how nucleotide-level mutation processes drive antibody evolution.

Why does selection feel so weak relative to mutation in affinity maturation? A new blog post giving three perspectives, including our new transformer-based model of natural selection on antibodies: matsen.group/general/202...

Origins and diversity of Greenland’s Qimmit revealed with genomes of ancient and modern sled dogs The Qimmeq (Greenland sled dog) has worked continuously with the Inuit in Greenland for more than 800 years. However, they now face drastic population declines caused by climate change, urbanization, ...

Read our study here:

doi.org/10.1126/scie...

Happy to announce that our study examining the genetic history of the Qimmeq (Greenland Sled Dog) came out today in Science.

@mhssinding.bsky.social
#qimmeq #dogs #palaeogenetics #greenland #greenlandsleddog @science.org #Ilisimatusarfik #globeinstitute #ucph #nih

Challenges for the Immunoglobulin and T cell receptor gene nomenclatures in the modern genomics era Antibodies were at the forefront of protein and gene research in the 1970s and 1980s [1–3]. At that time, every report of a new antibody gene or even a partial antibody gene was eagerly awaited, and s...

An overview of the future of IG and TR gene nomenclature www.immunoinformaticsjournal.com/article/S266...

@yanasafonova.bsky.social @elisarosix.bsky.social

Germline polymorphism in the immunoglobulin kappa and lambda loci explain variation in the expressed light chain antibody repertoire Variation in antibody (Ab) responses contributes to disease outcomes and therapeutic responsiveness, the determinants of which remain incompletely understood. This study demonstrates that polymorphism...

Turns out...just like in the antibody heavy chain repertoire, germline variants in the immunoglobulin lambda and kappa loci influence the composition of light chain B cell receptors!
Way to go Eric @e-engelbrecht1.bsky.social !!!!
www.biorxiv.org/content/10.1...

Cool germinal center acrobatics from Juhee Pae et al, check it out!

www.nature.com/articles/s41...

Trying out dplyr::consecutive_id() for a project today. #rstats

It generates a unique identifier that increments every time a variable (or combination of variables) changes.

It seems the registration link is dead, I get 404

This is a wonderful approach to an important question.
Many thanks!

The human immunoglobulin heavy chain constant gene locus is enriched for large complex structural variants and coding polymorphisms that vary in frequency among human populations The immunoglobulin heavy chain constant (IGHC) domain of antibodies (Ab) is responsible for a variety of effector functions critical to Ab mediated immunity. In human, this domain is encoded by genes ...

Did you know that human immunoglobulin constant genes are crazy diverse? It's got me thinking...Proud of Uddalok Jana! And grateful for collabs @guryaari.bsky.social @williamlees.bsky.social @ayeletperes.bsky.social @e-engelbrecht1.bsky.social @yscientist.bsky.social
www.biorxiv.org/content/10.1...

souporcell guys have introduced a feature to use known genotypes, so I thought the script for correlating clusters with the genotypes in Demuxafy became redundant. But I cannot figure out what souporcell is actually doing, when you supply those genotypes, so it's good the script is still there

Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid-onset dementia and death. However, elimination of endogenous PrP halts...

Insanely good news if this holds up.

Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor

www.science.org/doi/10.1126/...

Demuxafy: improvement in droplet assignment by integrating multiple single-cell demultiplexing and doublet detection methods - Genome Biology Recent innovations in single-cell RNA-sequencing (scRNA-seq) provide the technology to investigate biological questions at cellular resolution. Pooling cells from multiple individuals has become a com...

Words of appreciation for @drneavin.bsky.social and all of the contributors for Demuxafy.
They benchmarked and combined tools for demultiplexing SC RNA-seq using genotypes. Supplied evrth in a singularity container and (!!!) wrote CLEAR documentation

genomebiology.biomedcentral.com/articles/10....

AIRR Community Seminar Series - The Antibody Society Join the AIRR Community for a 90 minute “lab-style” virtual seminar. Each month an established and an early career scientist will discuss their AIRR-seq related research. Seminar time will be 16:00 – ...

First AIRR-C seminar of the year🎉 on January 30th at 4pm CET, 10am ET, 7am PT. antibodysociety.org/the-airr-com... With
Mikhail Pogorelyy (TIRTL-seq) and Eglantine Hector (inference of phylogeny and selection pressure in BCR sequences).

My guess is that it is done to normalize this kind of discussion, because before, it was simply unspeakable. Maybe also they're trying to evaluate the reaction

Why is he even doing this? That's not possible for it to make through Congress (2/3 majority in House and Senate), even less so to get it ratified by state legislatures.

Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut - Nature Microbiology Metagenomic immunoglobulin sequencing (MIg-seq) uncovered patterns of IgA antibody binding of bacterial strains in the healthy human gut microbiome.

Our technique for studying strain-level IgA binding in the microbiome is out now at @naturemicrobiol.bsky.social! Fascinated by IgA since Sean Spencer told me about it, here we make some fundamental discoveries about strain-level IgA dynamics in the healthy human gut (1/5) doi.org/10.1038/s415...

Happy to share our new collaborative work! 🚨 We analyzed 2250 TCR repertoires to uncover how HLA risk alleles shape immune autoreactivity in T1D. T1D-specific HLA-motifs were also validated in pancreatic lymph nodes (pLN) & spleen. 🧬🧵 #T1D #Immunology #TCR 1/9

Pinning this for myself: I am determined to be kinder, gentler on this site compared to the netherworld we left - more like how we behave in the real world. Will still have a lot of (ideally constructively) critical things to say & have plenty of arguments especially on controversial topics. But 1/

I’ve tried to put together a starter pack of immunologists/scientists exploring B Cell Repertoires and Antibody Affinities.

Please feel free to share/join!

go.bsky.app/4P64DmM

TIRTL-seq: Deep, quantitative, and affordable paired TCR repertoire sequencing α/β T cells are key players in adaptive immunity. The specificity of T cells is determined by the sequences of the hypervariable T cell receptor (TCR) α and β chains. Although bulk TCR sequencing offe...

We keep improving TIRTL-seq, see the updated preprint (www.biorxiv.org/content/10.1...)! New additions include: a manual 96-well protocol, code and raw data now available, and successful in vitro validation of EBV and SARS-CoV-2 TCRs.

#IUIS2025 is happening next year in Vienna, Austria, from August 17-22. Join us for a week of cutting-edge immunology, groundbreaking research, and global collaboration.
Early registration and abstract submissions are now OPEN at www.iuis2025.org! See you there! 🌍