F. A. Matsen
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View article: Nucleotide context models outperform protein language models for predicting antibody affinity maturation
Nucleotide context models outperform protein language models for predicting antibody affinity maturation Open
Antibodies play a crucial role in adaptive immunity. They develop as B cell receptors (BCRs): membrane-bound forms of antibodies that are expressed on the surfaces of B cells. BCRs are refined through affinity maturation, a process of soma…
View article: larch: mapping the parsimony-optimal landscape of trees for directed exploration
larch: mapping the parsimony-optimal landscape of trees for directed exploration Open
Phylogenetic inference algorithms for large data sets typically return a single tree. However, there are often many optimal trees, especially when sequence data is closely related. We develop a compact representation of large collections o…
View article: Separating selection from mutation in antibody language models
Separating selection from mutation in antibody language models Open
Antibodies are encoded by nucleotide sequences that are generated by V(D)J recombination and evolve according to mutation and selection processes. Existing antibody language models, however, focus exclusively on antibodies as strings of am…
View article: Inference of germinal center evolutionary dynamics via simulation-based deep learning
Inference of germinal center evolutionary dynamics via simulation-based deep learning Open
B cells and the antibodies they produce are vital to health and survival, motivating research on the details of the mutational and evolutionary processes in the germinal centers (GC) from which mature B cells arise. It is known that B cell…
View article: Thrifty wide-context models of B cell receptor somatic hypermutation
Thrifty wide-context models of B cell receptor somatic hypermutation Open
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, understanding the selective forces guiding affinity maturation, and under…
View article: A Sitewise Model of Natural Selection on Individual Antibodies via a Transformer–Encoder
A Sitewise Model of Natural Selection on Individual Antibodies via a Transformer–Encoder Open
During affinity maturation, antibodies are selected for their ability to fold and to bind a target antigen between rounds of somatic hypermutation. Previous studies have identified patterns of selection in antibodies using B cell repertoir…
View article: Thrifty wide-context models of B cell receptor somatic hypermutation
Thrifty wide-context models of B cell receptor somatic hypermutation Open
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, for understanding the selective forces guiding affinity maturation, and f…
View article: <tt>torchtree</tt>: Flexible Phylogenetic Model Development and Inference Using PyTorch
torchtree: Flexible Phylogenetic Model Development and Inference Using PyTorch Open
Bayesian inference has predominantly relied on the Markov chain Monte Carlo (MCMC) algorithm for many years. However, MCMC is computationally laborious, especially for complex phylogenetic models of time trees. This bottleneck has led to t…
View article: Nucleotide context models outperform protein language models for predicting antibody affinity maturation
Nucleotide context models outperform protein language models for predicting antibody affinity maturation Open
Antibodies play a crucial role in adaptive immunity. They develop as B cell receptors (BCRs): membrane-bound forms of antibodies that are expressed on the surfaces of B cells. BCRs are refined through affinity maturation, a process of soma…
View article: Biological causes and impacts of rugged tree landscapes in phylodynamic inference
Biological causes and impacts of rugged tree landscapes in phylodynamic inference Open
Phylodynamic analysis has been instrumental in elucidating epidemiological and evolutionary dynamics of pathogens. Bayesian phylodynamics integrates out phylogenetic uncertainty, which is typically substantial in phylodynamic datasets due …
View article: Replaying germinal center evolution on a quantified affinity landscape
Replaying germinal center evolution on a quantified affinity landscape Open
Darwinian evolution of immunoglobulin genes within germinal centers (GC) underlies the progressive increase in antibody affinity following antigen exposure. Whereas the mechanics of how competition between GC B cells drives increased affin…
View article: Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies
Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies Open
Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisit…
View article: The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure
The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure Open
RNA viruses like SARS-CoV-2 have high mutation rates, which contribute to their rapid evolution. Mutation rates depend on mutation type and can vary between sites in a virus’s genome. Understanding this variation can shed light on the muta…
View article: Statistical analysis of repertoire data demonstrates the influence of microhomology in V(D)J recombination
Statistical analysis of repertoire data demonstrates the influence of microhomology in V(D)J recombination Open
V(D)J recombination generates the diverse B and T cell receptors essential for recognizing a wide array of antigens. This diversity arises from the combinatorial assembly of V(D)J genes and the junctional deletion and insertion of nucleoti…
View article: Thrifty wide-context models of B cell receptor somatic hypermutation
Thrifty wide-context models of B cell receptor somatic hypermutation Open
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, for understanding the selective forces guiding affinity maturation, and f…
View article: Thrifty wide-context models of B cell receptor somatic hypermutation
Thrifty wide-context models of B cell receptor somatic hypermutation Open
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, understanding the selective forces guiding affinity maturation, and under…
View article: Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-class antibodies
Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-class antibodies Open
Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisit…
View article: Leveraging DAGs to improve context-sensitive and abundance-aware tree estimation
Leveraging DAGs to improve context-sensitive and abundance-aware tree estimation Open
The phylogenetic inference package GCtree uses abundance of sampled sequences to improve the performance of parsimony-based inference, using a branching process model. Our previous work showed that GCtree performs competitively on B-cell r…
View article: PhyloVAE: Unsupervised Learning of Phylogenetic Trees via Variational Autoencoders.
PhyloVAE: Unsupervised Learning of Phylogenetic Trees via Variational Autoencoders. Open
Learning informative representations of phylogenetic tree structures is essential for analyzing evolutionary relationships. Classical distance-based methods have been widely used to project phylogenetic trees into Euclidean space, but they…
View article: Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies
Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies Open
SARS-CoV-2 rapidly evolves to evade human immunity. While the virus's overall resistance to human polyclonal antibody responses has steadily increased over time, the dynamics by which it escaped individual monoclonal antibodies within thes…
View article: The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure
The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure Open
RNA viruses like SARS-CoV-2 have a high mutation rate, which contributes to their rapid evolution. The rate of mutations depends on the mutation type (e.g., A → C , A → G , etc.) and can vary between sites in the viral genome. Understandin…
View article: Thrifty wide-context models of B cell receptor somatic hypermutation
Thrifty wide-context models of B cell receptor somatic hypermutation Open
Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, for understanding the selective forces guiding affinity maturation, and f…
View article: TreeFormer: A transformer-based tree rearrangement operation for phylogenetic reconstruction
TreeFormer: A transformer-based tree rearrangement operation for phylogenetic reconstruction Open
Phylogenetic inference is a fundamental problem in biology, which studies the origins and evolutionary relationships among species. Popular phylogenetic inference methods, such as IQ-TREE, RAxML, and PHYML, typically utilize heuristic tree…
View article: Phylogenetic Tree Instability After Taxon Addition: Empirical Frequency, Predictability, and Consequences For Online Inference
Phylogenetic Tree Instability After Taxon Addition: Empirical Frequency, Predictability, and Consequences For Online Inference Open
Online phylogenetic inference methods add sequentially arriving sequences to an inferred phylogeny without the need to recompute the entire tree from scratch. Some online method implementations exist already, but there remains concern that…
View article: Statistical analysis of repertoire data demonstrates the influence of microhomology in V(D)J recombination
Statistical analysis of repertoire data demonstrates the influence of microhomology in V(D)J recombination Open
V(D)J recombination generates the diverse B and T cell receptors essential for recognizing a wide array of antigens. This diversity arises from the combinatorial assembly of V(D)J genes and the junctional deletion and insertion of nucleoti…
View article: Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff
Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff Open
The cytochrome P450s enzyme family metabolizes ∼80% of small molecule drugs. Variants in cytochrome P450s can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservati…