Biological sequences do not come at random. Instead, they appear with particular frequencies that reflect properties of the associated system or phenomenon. Knowing how biological sequences are distributed in sequence space is thus a natural first step toward understanding the underlying mechanisms.
View Article and Find Full Text PDFBiological sequences do not come at random. Instead, they appear with particular frequencies that reflect properties of the associated system or phenomenon. Knowing how biological sequences are distributed in sequence space is thus a natural first step toward understanding the underlying mechanisms.
View Article and Find Full Text PDFSialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications and diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy and metastasis. Sialyltransferases thus represent emerging targets for the development of small molecule cancer drugs.
View Article and Find Full Text PDFContemporary high-throughput mutagenesis experiments are providing an increasingly detailed view of the complex patterns of genetic interaction that occur between multiple mutations within a single protein or regulatory element. By simultaneously measuring the effects of thousands of combinations of mutations, these experiments have revealed that the genotype-phenotype relationship typically reflects not only genetic interactions between pairs of sites but also higher-order interactions among larger numbers of sites. However, modeling and understanding these higher-order interactions remains challenging.
View Article and Find Full Text PDFDensity estimation in sequence space is a fundamental problem in machine learning that is also of great importance in computational biology. Due to the discrete nature and large dimensionality of sequence space, how best to estimate such probability distributions from a sample of observed sequences remains unclear. One common strategy for addressing this problem is to estimate the probability distribution using maximum entropy (i.
View Article and Find Full Text PDFEmerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENV) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIKV) has created an international public health emergency because ZIKV infection has been linked to congenital defects and Guillain-Barré syndrome.
View Article and Find Full Text PDFHow might a smooth probability distribution be estimated with accurately quantified uncertainty from a limited amount of sampled data? Here we describe a field-theoretic approach that addresses this problem remarkably well in one dimension, providing an exact nonparametric Bayesian posterior without relying on tunable parameters or large-data approximations. Strong non-Gaussian constraints, which require a nonperturbative treatment, are found to play a major role in reducing distribution uncertainty. A software implementation of this method is provided.
View Article and Find Full Text PDFRecent progress in the determination of both masses and radii of neutron stars is starting to place stringent constraints on the dense matter equation of state. In particular, new theoretical developments together with improved statistical tools seem to favor stellar radii that are significantly smaller than those predicted by models using purely nucleonic equations of state. Given that the underlying equation of state must also account for the observation of 2M⊙ neutron stars, theoretical approaches to the study of the dense matter equation of state are facing serious challenges.
View Article and Find Full Text PDF