Two-dimensional semi-parametric alignment of chromatograms.

We present a comprehensive alignment algorithm that extends the semi-parametric approach to two dimensions. The algorithm is based on modeling shifts with a two-dimensional "warp function" such that the sample chromatogram - its shifts corrected with the warp function - is adjusted to the reference chromatogram by minimizing the squared intensity difference. A warp function approach has the advantage that overlapping peaks are easily dealt with compared to other proposed two-dimensional algorithms. Another advantage is that missing peaks are allowed if the absence of these peaks has little numerical effect on the warp function computation and if these peaks occur between existing peaks. Performance of the algorithm is demonstrated using GC×GC data from three batches of three diesel oil samples and LC-MS data from a mouse breast cancer data set.

Microarray analysis of bleomycin-exposed lymphoblastoid cells for identifying cancer susceptibility genes.

The uncovering of genes involved in susceptibility to the sporadic cancer types is a great challenge. It is well established that the way in which an individual deals with DNA damage is related to the chance to develop cancer. Mutagen sensitivity is a phenotype that reflects an individual's susceptibility to the major sporadic cancer types, including colon, lung, and head and neck cancer. A standard test for mutagen sensitivity is measuring the number of chromatid breaks in lymphocytes after exposure to bleomycin. The aim of the present study was to search for the pathways involved in mutagen sensitivity. Lymphoblastoid cell lines of seven individuals with low mutagen sensitivity were compared with seven individuals with a high score. RNA was isolated from cells exposed to bleomycin (4 hours) and from unexposed cells. Microarray analysis (19K) was used to compare gene expression of insensitive and sensitive cells. The profile of most altered genes after bleomycin exposure, analyzed in all 14 cell lines, included relatively many genes involved in biological processes, such as cell growth and/or maintenance, proliferation, and regulation of cell cycle, as well as some genes involved in DNA repair. When comparing the insensitive and sensitive individuals, other differentially expressed genes were found that are involved in signal transduction and cell growth and/or maintenance (e.g., BUB1 and DUSP4). This difference in expression profiles between mutagen-sensitive and mutagen-insensitive individuals justifies further studies aimed at elucidating the genes responsible for the development of sporadic cancers.

Morphine exposure and abstinence define specific stages of gene expression in the rat nucleus accumbens.

Intermittent exposure to addictive drugs causes long-lasting changes in responsiveness to these substances due to persistent molecular and cellular alterations within the meso-corticolimbic system. In this report, we studied the expression profiles of 159 genes in the rat nucleus accumbens during morphine exposure (14 days, 10 mg/kg s.c.) and drug-abstinence (3 weeks). We used real-time quantitative PCR to monitor gene expression after establishing its sensitivity and resolution to resolve small changes in expression for genes in various abundance classes. Morphine-exposure (5 time points) and subsequent abstinence (6 time points) induced phase-specific temporal gene expression of distinct functional groups of genes, for example, short-term homeostatic responses. Opiate withdrawal appeared to be a new stimulus in terms of gene expression and mediates a marked wave of gene repression. Prolonged abstinence resulted in persistently changed expression levels of genes involved in neuronal outgrowth and re-wiring. Our findings substantiate the hypothesis that this new gene program, initiated upon morphine-withdrawal, may subserve long-term neuronal plasticity involved in the persistent behavioral consequences of repeated drug-exposure.