Random Partition Distribution Indexed by Pairwise Information.

We propose a random partition distribution indexed by pairwise similarity information such that partitions compatible with the similarities are given more probability. The use of pairwise similarities, in the form of distances, is common in some clustering algorithms (e.g.

KScons: a Bayesian approach for protein residue contact prediction using the knob-socket model of protein tertiary structure.

Motivation: By simplifying the many-bodied complexity of residue packing into patterns of simple pairwise secondary structure interactions between a single knob residue with a three-residue socket, the knob-socket construct allows a more direct incorporation of structural information into the prediction of residue contacts. By modeling the preferences between the amino acid composition of a socket and knob, we undertake an investigation of the knob-socket construct's ability to improve the prediction of residue contacts. The statistical model considers three priors and two posterior estimations to better understand how the input data affects predictions.

Bayesian model of protein primary sequence for secondary structure prediction.

Determining the primary structure (i.e., amino acid sequence) of a protein has become cheaper, faster, and more accurate.

Understanding the general packing rearrangements required for successful template based modeling of protein structure from a CASP experiment.

As an alternative to the common template based protein structure prediction methods based on main-chain position, a novel side-chain centric approach has been developed. Together with a Bayesian loop modeling procedure and a combination scoring function, the Stone Soup algorithm was applied to the CASP9 set of template based modeling targets. Although the method did not generate as large of perturbations to the template structures as necessary, the analysis of the results gives unique insights into the differences in packing between the target structures and their templates.

A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response.

Background: Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly affecting the health and well-being of the host. Thus, it is important to develop a synthetic approach to study the host transcriptome and the microbiome simultaneously. Early microbial colonization in infants is critically important for directing neonatal intestinal and immune development, and is especially attractive for studying the development of human-commensal interactions.

Near-native protein loop sampling using nonparametric density estimation accommodating sparcity.

Unlike the core structural elements of a protein like regular secondary structure, template based modeling (TBM) has difficulty with loop regions due to their variability in sequence and structure as well as the sparse sampling from a limited number of homologous templates. We present a novel, knowledge-based method for loop sampling that leverages homologous torsion angle information to estimate a continuous joint backbone dihedral angle density at each loop position. The φ,ψ distributions are estimated via a Dirichlet process mixture of hidden Markov models (DPM-HMM).

Characterizing the regularity of tetrahedral packing motifs in protein tertiary structure.

Motivation: While protein secondary structure is well understood, representing the repetitive nature of tertiary packing in proteins remains difficult. We have developed a construct called the relative packing group (RPG) that applies the clique concept from graph theory as a natural basis for defining the packing motifs in proteins. An RPG is defined as a clique of residues, where every member contacts all others as determined by the Delaunay tessellation.

A DIRICHLET PROCESS MIXTURE OF HIDDEN MARKOV MODELS FOR PROTEIN STRUCTURE PREDICTION.

By providing new insights into the distribution of a protein's torsion angles, recent statistical models for this data have pointed the way to more efficient methods for protein structure prediction. Most current approaches have concentrated on bivariate models at a single sequence position. There is, however, considerable value in simultaneously modeling angle pairs at multiple sequence positions in a protein.

Density Estimation for Protein Conformation Angles Using a Bivariate von Mises Distribution and Bayesian Nonparametrics.

Interest in predicting protein backbone conformational angles has prompted the development of modeling and inference procedures for bivariate angular distributions. We present a Bayesian approach to density estimation for bivariate angular data that uses a Dirichlet process mixture model and a bivariate von Mises distribution. We derive the necessary full conditional distributions to fit the model, as well as the details for sampling from the posterior predictive distribution.

The contributions of molecular framework to IMS collision cross-sections of gas-phase peptide ions.

Molecular dynamics (MD) is an essential tool for correlating collision cross-section data determined by ion mobility spectrometry (IMS) with candidate (calculated) structures. Conventional methods used for ion structure determination rely on comparing the measured cross-sections with the calculated collision cross-section for the lowest energy structure(s) taken from a large pool of candidate structures generated through multiple tiers of simulated annealing. We are developing methods to evaluate candidate structures from an ensemble of many conformations rather than the lowest energy structure.

Spiked Dirichlet Process Prior for Bayesian Multiple Hypothesis Testing in Random Effects Models.

We propose a Bayesian method for multiple hypothesis testing in random effects models that uses Dirichlet process (DP) priors for a nonparametric treatment of the random effects distribution. We consider a general model formulation which accommodates a variety of multiple treatment conditions. A key feature of our method is the use of a product of spiked distributions, i.

Assessing side-chain perturbations of the protein backbone: a knowledge-based classification of residue Ramachandran space.

Grouping the 20 residues is a classic strategy to discover ordered patterns and insights about the fundamental nature of proteins, their structure, and how they fold. Usually, this categorization is based on the biophysical and/or structural properties of a residue's side-chain group. We extend this approach to understand the effects of side chains on backbone conformation and to perform a knowledge-based classification of amino acids by comparing their backbone phi, psi distributions in different types of secondary structure.

Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma.

To identify the molecular mechanisms by which EBV-associated epithelial cancers are maintained, we measured the expression of essentially all human genes and all latent EBV genes in a collection of 31 laser-captured, microdissected nasopharyngeal carcinoma (NPC) tissue samples and 10 normal nasopharyngeal tissues. Global gene expression profiles clearly distinguished tumors from normal healthy epithelium. Expression levels of six viral genes (EBNA1, EBNA2, EBNA3A, EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely correlated with the expression of a large subset of host genes.

Accommodative ciliary body and lens function in rhesus monkeys, I: normal lens, zonule and ciliary process configuration in the iridectomized eye.

Purpose: The underlying causes of presbyopia, and the functional relationship between the ciliary muscle and lens during aging are unclear. In the current study, these relationships were studied in rhesus monkeys, whose accommodative apparatus and age-related loss of accommodation are similar to those in humans.

Methods: Centripetal ciliary body and lens equator movements were measured during accommodation in 28 eyes of 21 rhesus monkeys (ages, 5.

Vitreous glutamate concentration and axon loss in monkeys with experimental glaucoma.

Objective: To evaluate vitreous glutamate concentration and axon loss in monkeys with experimental glaucoma.

Methods: We induced unilateral chronic glaucoma by means of laser trabecular destruction in 14 rhesus and 6 cynomolgus monkeys. Intraocular pressure (IOP) was monitored weekly.