Discovering Genetic Modulators of the Protein Homeostasis System through Multilevel Analysis.

Every protein progresses through a natural lifecycle from birth to maturation to death; this process is coordinated by the protein homeostasis system. Environmental or physiological conditions trigger pathways that maintain the homeostasis of the proteome. An open question is how these pathways are modulated to respond to the many stresses that an organism encounters during its lifetime.

Model-based identification of conditionally-essential genes from transposon-insertion sequencing data.

The understanding of bacterial gene function has been greatly enhanced by recent advancements in the deep sequencing of microbial genomes. Transposon insertion sequencing methods combines next-generation sequencing techniques with transposon mutagenesis for the exploration of the essentiality of genes under different environmental conditions. We propose a model-based method that uses regularized negative binomial regression to estimate the change in transposon insertions attributable to gene-environment changes in this genetic interaction study without transformations or uniform normalization.

A BAYESIAN NONPARAMETRIC MODEL FOR INFERRING SUBCLONAL POPULATIONS FROM STRUCTURED DNA SEQUENCING DATA.

There are distinguishing features or "hallmarks" of cancer that are found across tumors, individuals, and types of cancer, and these hallmarks can be driven by specific genetic mutations. Yet, within a single tumor there is often extensive genetic heterogeneity as evidenced by single-cell and bulk DNA sequencing data. The goal of this work is to jointly infer the underlying genotypes of tumor subpopulations and the distribution of those subpopulations in individual tumors by integrating single-cell and bulk sequencing data.

SCSIM: Jointly simulating correlated single-cell and bulk next-generation DNA sequencing data.

Background: Recently, it has become possible to collect next-generation DNA sequencing data sets that are composed of multiple samples from multiple biological units where each of these samples may be from a single cell or bulk tissue. Yet, there does not yet exist a tool for simulating DNA sequencing data from such a nested sampling arrangement with single-cell and bulk samples so that developers of analysis methods can assess accuracy and precision.

Results: We have developed a tool that simulates DNA sequencing data from hierarchically grouped (correlated) samples where each sample is designated bulk or single-cell.

Methods to estimate aspects of physical activity and sedentary behavior from high-frequency wrist accelerometer measurements.

This investigation developed models to estimate aspects of physical activity and sedentary behavior from three-axis high-frequency wrist-worn accelerometer data. The models were developed and tested on 20 participants (n = 10 males, n = 10 females, mean age = 24.1, mean body mass index = 23.