Representing and decomposing genomic structural variants as balanced integer flows on sequence graphs

The study of genomic variation has provided key insights into the functional role of mutations. Predominantly, studies have focused on single nucleotide variants (SNV), which are relatively easy to detect and can be described with rich mathematical models. However, it has been observed that genomes are highly plastic, and that whole regions can be moved, removed or duplicated in bulk. These structural variants (SV) have been shown to have significant impact on the phenotype, but their study has been held back by the combinatorial complexity of the underlying models. We describe here a general model of structural variation that encompasses both balanced rearrangements and arbitrary copy-numbers variants (CNV). In this model, we show that the space of possible evolutionary histories that explain the structural differences between any two genomes can be sampled ergodically

Genome-wide Protein-chemical Interaction Prediction

The analysis of protein-chemical reactions on a large scale is critical to understanding the complex interrelated mechanisms that govern biological life at the cellular level. Chemical proteomics is a new research area aimed at genome-wide screening of such chemical-protein interactions. Traditional approaches to such screening involve in vivo or in vitro experimentation, which while becoming faster with the application of high-throughput screening technologies, remains costly and time-consuming compared to in silico methods. Early in silico methods are dependant on knowing 3D protein structures (docking) or knowing binding information for many chemicals (ligand-based approaches). Typical machine learning approaches follow a global classification approach where a single predictive model is trained for an entire data set, but such an approach is unlikely to generalize well to the protein-chemical interaction space considering its diversity and heterogeneous distribution. In response to the global approach, work on local models has recently emerged to improve generalization across the interaction space by training a series of independant models localized to each predict a single interaction. This work examines current approaches to genome-wide protein-chemical interaction prediction and explores new computational methods based on modifications to the boosting framework for ensemble learning. The methods are described and compared to several competing classification methods. Genome-wide chemical-protein interaction data sets are acquired from publicly available resources, and a series of experimental studies are performed in order to compare the the performance of each method under a variety of conditions

Current Challenges in Modeling Cellular Metabolism

Mathematical and computational models play an essential role in understanding the cellular metabolism. They are used as platforms to integrate current knowledge on a biological system and to systematically test and predict the effect of manipulations to such systems. The recent advances in genome sequencing techniques have facilitated the reconstruction of genome-scale metabolic networks for a wide variety of organisms from microbes to human cells. These models have been successfully used in multiple biotechnological applications. Despite these advancements, modeling cellular metabolism still presents many challenges. The aim of this Research Topic is not only to expose and consolidate the state-of-the-art in metabolic modeling approaches, but also to push this frontier beyond the current edge through the introduction of innovative solutions. The articles presented in this e-book address some of the main challenges in the field, including the integration of different modeling formalisms, the integration of heterogeneous data sources into metabolic models, explicit representation of other biological processes during phenotype simulation, and standardization efforts in the representation of metabolic models and simulation results

Computer Science Research Institute 2004 annual report of activities.

This report summarizes the activities of the Computer Science Research Institute (CSRI) at Sandia National Laboratories during the period January 1, 2004 to December 31, 2004. During this period the CSRI hosted 166 visitors representing 81 universities, companies and laboratories. Of these 65 were summer students or faculty. The CSRI partially sponsored 2 workshops and also organized and was the primary host for 4 workshops. These 4 CSRI sponsored workshops had 140 participants--74 from universities, companies and laboratories, and 66 from Sandia. Finally, the CSRI sponsored 14 long-term collaborative research projects and 5 Sabbaticals