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Antibodies, an essential part of our immune system, develop through an intricate process to bind a wide array of pathogens. This process involves randomly mutating DNA sequences encoding these antibodies to find variants with improved binding, though mutations are not distributed uniformly across sequence sites. Immunologists observe this nonuniformity to be consistent with mutation motifs, which are short DNA subsequences that affect how likely a given site is to experience a mutation. Quantifying the effect of motifs on mutation rates is challenging: a large number of possible motifs makes this statistical problem high dimensional, while the unobserved history of the mutation process leads to a nontrivial missing data problem. We introduce an $ell_1$-penalized proportional hazards model to infer mutation motifs and their effects. In order to estimate model parameters, our method uses a Monte Carlo EM algorithm to marginalize over the unknown ordering of mutations. We show that our method performs better on simulated data compared to current methods and leads to more parsimonious models. The application of proportional hazards to mutation processes is, to our knowledge, novel and formalizes the current methods in a statistical framework that can be easily extended to analyze the effect of other biological features on mutation rates.
The fitness of a biological strategy is typically measured by its expected reproductive rate, the first moment of its offspring distribution. However, strategies with high expected rates can also have high probabilities of extinction. A similar situa
In the process of clinical diagnosis and treatment, the restricted mean survival time (RMST), which reflects the life expectancy of patients up to a specified time, can be used as an appropriate outcome measure. However, the RMST only calculates the
Smooth backfitting has proven to have a number of theoretical and practical advantages in structured regression. Smooth backfitting projects the data down onto the structured space of interest providing a direct link between data and estimator. This
The success of DNA nanotechnology has been driven by the discovery of novel structural motifs with a wide range of shapes and uses. We present a comprehensive study of the T-motif, a 3-armed, planar, right-angled junction that has been used in the se
Motivated by the classical Susceptible-Infected-Recovered (SIR) epidemic models proposed by Kermack and Mckendrick, we consider a class of stochastic compartmental dynamical systems with a notion of partial ordering among the compartments. We call su