Genes related to emphysema are enriched for ubiquitination pathways.

Background: Increased small airway resistance and decreased lung elasticity contribute to the airflow limitation in chronic obstructive pulmonary disease (COPD). The lesion that corresponds to loss of lung elasticity is emphysema; the small airway obstruction is due to inflammatory narrowing and obliteration. Despite their convergence in altered physiology, different mechanisms contribute to these processes.

Biomarkers of the Hedgehog/Smoothened pathway in healthy volunteers.

The Hedgehog (Hh) pathway is involved in oncogenic transformation and tumor maintenance. The primary objective of this study was to select surrogate tissue to measure messenger ribonucleic acid (mRNA) levels of Hh pathway genes for measurement of pharmacodynamic effect. Expression of Hh pathway specific genes was measured by quantitative real time polymerase chain reaction (qRT-PCR) and global gene expression using Affymetrix U133 microarrays.

A gene expression signature that classifies human atherosclerotic plaque by relative inflammation status.

Background: Atherosclerosis is a complex disease requiring improvements in diagnostic techniques and therapeutic treatments. Both improvements will be facilitated by greater exploration of the biology of atherosclerotic plaque. To this end, we carried out large-scale gene expression analysis of human atherosclerotic lesions.

Gene expression profiling in patients with chronic obstructive pulmonary disease and lung cancer.

Rationale: Chronic obstructive lung disease (COPD) is a common and disabling lung disease for which there are few therapeutic options.

Objectives: We reasoned that gene expression profiling of COPD lungs could reveal previously unidentified disease pathways.

Methods: Forty-eight human lung samples were obtained from tissue resected from five nonsmokers, 21 GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0, 9 GOLD stage 1, 10 GOLD stage 2, and 3 GOLD stage 3 patients.

Pathway and gene-set activation measurement from mRNA expression data: the tissue distribution of human pathways.

Background: Interpretation of lists of genes or proteins with altered expression is a critical and time-consuming part of microarray and proteomics research, but relatively little attention has been paid to methods for extracting biological meaning from these output lists. One powerful approach is to examine the expression of predefined biological pathways and gene sets, such as metabolic and signaling pathways and macromolecular complexes. Although many methods for measuring pathway expression have been proposed, a systematic analysis of the performance of multiple methods over multiple independent data sets has not previously been reported.

Rosetta error model for gene expression analysis.

Motivation: In microarray gene expression studies, the number of replicated microarrays is usually small because of cost and sample availability, resulting in unreliable variance estimation and thus unreliable statistical hypothesis tests. The unreliable variance estimation is further complicated by the fact that the technology-specific variance is intrinsically intensity-dependent.

Results: The Rosetta error model captures the variance-intensity relationship for various types of microarray technologies, such as single-color arrays and two-color arrays.

Individual-specific variation of gene expression in peripheral blood leukocytes.

DNA microarray technology is used to determine gene expression profiles of various cell types, especially abnormal cells, such as cancer. By contrast, relatively little attention has been given to expression profiling of normal tissues. Here we describe studies of gene expression in peripheral blood leukocytes (PBL) from normal individuals sampled multiple times over periods ranging from several weeks up to 6 months.

Signatures of environmental exposures using peripheral leukocyte gene expression: tobacco smoke.

Functional biological markers of environmental exposures are important in epidemiological studies of disease risk. Such markers not only provide a measure of the exposure, they also reflect the degree of physiological and biochemical response to the exposure. In an observational study, using DNA microarrays, we show that it is possible to distinguish between 85 individuals exposed and unexposed to tobacco smoke on the basis of mRNA expression in peripheral leukocytes.

Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.

Modern medicine faces the challenge of developing safer and more effective therapies to treat human diseases. Many drugs currently in use were discovered without knowledge of their underlying molecular mechanisms. Understanding their biological targets and modes of action will be essential to design improved second-generation compounds.

Microarray standard data set and figures of merit for comparing data processing methods and experiment designs.

Motivation: There is a very large and growing level of effort toward improving the platforms, experiment designs, and data analysis methods for microarray expression profiling. Along with a growing richness in the approaches there is a growing confusion among most scientists as to how to make objective comparisons and choices between them for different applications. There is a need for a standard framework for the microarray community to compare and improve analytical and statistical methods.

Use of hybridization kinetics for differentiating specific from non-specific binding to oligonucleotide microarrays.

Hybridization kinetics were found to be significantly different for specific and non-specific binding of labeled cRNA to surface-bound oligonucleotides on microarrays. We show direct evidence that in a complex sample specific binding takes longer to reach hybridization equilibrium than the non- specific binding. We find that this property can be used to estimate and to correct for the hybridization contributed by non-specific binding.