An integrated Bayesian analysis of LOH and copy number data

BACKGROUND Cancer and other disorders are due to genomic lesions. SNP-microarrays are able to measure simultaneously both genotype and copy number (CN) at several Single Nucleotide Polymorphisms (SNPs) along the genome. CN is defined as the number of DNA copies, and the normal is two, since we have two copies of each chromosome. The genotype of a SNP is the status given by the nucleotides (alleles) which are present on the two copies of DNA. It is defined homozygous or heterozygous if the two alleles are the same or if they differ, respectively. Loss of heterozygosity (LOH) is the loss of the heterozygous status due to genomic events. Combining CN and LOH data, it is possible to better identify different types of genomic aberrations. For example, a long sequence of homozygous SNPs might be caused by either the physical loss of one copy or a uniparental disomy event (UPD), i.e. each SNP has two identical nucleotides both derived from only one parent. In this situation, the knowledge of the CN can help in distinguishing between these two events. RESULTS To better identify genomic aberrations, we propose a method (called gBPCR) which infers the type of aberration occurred, taking into account all the possible influence in the microarray detection of the homozygosity status of the SNPs, resulting from an altered CN level. Namely, we model the distributions of the detected genotype, given a specific genomic alteration and we estimate the parameters involved on public reference datasets. The estimation is performed similarly to the modified Bayesian Piecewise Constant Regression, but with improved estimators for the detection of the breakpoints.Using artificial and real data, we evaluate the quality of the estimation of gBPCR and we also show that it outperforms other well-known methods for LOH estimation. CONCLUSIONS We propose a method (gBPCR) for the estimation of both LOH and CN aberrations, improving their estimation by integrating both types of data and accounting for their relationships. Moreover, gBPCR performed very well in comparison with other methods for LOH estimation and the estimated CN lesions on real data have been validated with another technique.This work was supported by Swiss National Science Foundation (grants 205321-112430, 205320-121886/1); Oncosuisse grants OCS-1939-8-2006 and OCS - 02296-08-2008; Cantone Ticino ("Computational life science/Ticino in rete” program); Fondazione per la Ricerca e la Cura sui Linfomi (Lugano, Switzerland)

Integrated analysis and applications

A select overview is provided of ongoing research focusing on the development and verification of integrated structural analysis and optimal design capabilities for advanced aerospace propulsion and power systems. Subjects discussed include the following: (1) Composites - analytical models (composite mechanics), integrated computational methods, and characterization of composite structural response and durability for resin-, metal-, and ceramic-matrix systems; (2) Advanced inelastic analysis - algorithm/numerical methods for more accurate and efficient analysis; (3) Constitutive modeling - theoretical formulation and characterization of thermoviscoplastic material behavior; (4) Computational simulation - engine structures from components to assembly, and up to an entire engine system subjected to simulated test-stand and mission load histories; (5) Probabilistic structural analysis - quantification of the effects of uncertainty in geometry, material, loads, and boundary conditions on structural response for true reliability assessment; and (6) Interdisciplinary optimization - incorporation of mathematical optimization and multidisciplinary analyses to provide streamlined, autonomous optimal design systems

Annual Energy Outlook

The Annual Energy Outlook 1997 (AEO97) presents midterm forecasts of energy supply, demand, and prices through 2015 prepared by the Energy Information Administration (EIA). These projections are based on results of EIA`s National Energy Modeling System (NEMS). This report begins with a summary of the reference case, followed by a discussion of the legislative assumptions and evolving legislative and regulatory issues. ``Issues in Focus`` discusses emerging energy issues and other topics of particular interest. It is followed by the analysis of energy market trends. The analysis in AEO97 focuses primarily on a reference case and four other cases that assume higher and lower economic growth and higher and lower world oil prices than in the reference case. Forecast tables for these cases are provided in Appendixes A through C. Appendixes D and E present summaries of the reference case forecasts in units of oil equivalence and household energy expenditures. Twenty-three other cases explore the impacts of varying key assumptions in NEMS--generally, technology penetration, with the major results shown in Appendix F. Appendix G briefly describes NEMS and the major AEO97 assumptions, with a summary table. 114 figs., 22 tabs

Annual Energy Outlook

The Annual Energy Outlook 1998 (AEO98) is the first AEO with projections to 2020. Key issues for the forecast extension are trends in energy efficiency improvements, the effects of increasing production and productivity improvements on energy prices, and the reduction in nuclear generating capacity. Projections in AEO98 also reflect a greater shift to electricity market restructuring. Restructuring is addressed through several changes that are assumed to occur in the industry, including a shorter capital recovery period for capacity expansion decisions and a revised financial structure that features a higher cost of capital as the result of higher competitive risk. Both assumptions tend to favor less capital-intensive generation technologies, such as natural gas, over coal or baseload renewable technologies. The forecasts include specific restructuring plans in those regions that have announced plans. California, New York, and New England are assumed to begin competitive pricing in 1998. The provisions of the California legislation for stranded cost recovery and price caps are incorporated. In New York and New England, stranded cost recovery is assumed to be phased out by 2008

Career Development: An Integrated Analysis

Career theories are developed to help us make sense of the complexity of career choice and development. The intricacy of the subject matter is such that career theories most often focus on one or two aspects of the phenomenon. As such the challenges of integrating the theories with each other, and integrating them within career practice, are not insignificant. In this chapter, I offer an overview of the theoretical landscape which illustrates how the theories align with each other to build up a comprehensive picture of career choice and development. The chapter will introduce a wide range of theoretical frameworks, spanning seven decades and numerous academic disciplines, and will discuss the most well-known theorists alongside less familiar names. The chapter will be structured around four concepts: identity, environment, career learning, and psychological career resources, and suggestions are offered for the incorporation of theories in career practice

Integrated analysis of engine structures

The need for light, durable, fuel efficient, cost effective aircraft requires the development of engine structures which are flexible, made from advaced materials (including composites), resist higher temperatures, maintain tighter clearances and have lower maintenance costs. The formal quantification of any or several of these requires integrated computer programs (multilevel and/or interdisciplinary analysis programs interconnected) for engine structural analysis/design. Several integrated analysis computer prorams are under development at Lewis Reseach Center. These programs include: (1) COBSTRAN-Composite Blade Structural Analysis, (2) CODSTRAN-Composite Durability Structural Analysis, (3) CISTRAN-Composite Impact Structural Analysis, (4) STAEBL-StruTailoring of Engine Blades, and (5) ESMOSS-Engine Structures Modeling Software System. Three other related programs, developed under Lewis sponsorship, are described

Analysis of integrated single-electron memory operation

Various aspects of single-electron memory are discussed. In particular, we analyze the single-electron charging by Fowler-Nordheim tunneling, propose the idea of background charge compensation, and discuss the defect-tolerant architecture based on nanofuses.Comment: 6 page