52 research outputs found
Detection of recurrent copy number alterations in the genome: taking among-subject heterogeneity seriously
Se adjunta un fichero pdf con los datos de investigación titulado "Supplementary Material for \Detection of Recurrent Copy
Number Alterations in the Genome: taking among-subject
heterogeneity seriously"Background: Alterations in the number of copies of genomic DNA that are common or recurrent
among diseased individuals are likely to contain disease-critical genes. Unfortunately, defining
common or recurrent copy number alteration (CNA) regions remains a challenge. Moreover, the
heterogeneous nature of many diseases requires that we search for common or recurrent CNA
regions that affect only some subsets of the samples (without knowledge of the regions and subsets
affected), but this is neglected by most methods.
Results: We have developed two methods to define recurrent CNA regions from aCGH data.
Our methods are unique and qualitatively different from existing approaches: they detect regions
over both the complete set of arrays and alterations that are common only to some subsets of the
samples (i.e., alterations that might characterize previously unknown groups); they use probabilities
of alteration as input and return probabilities of being a common region, thus allowing researchers
to modify thresholds as needed; the two parameters of the methods have an immediate,
straightforward, biological interpretation. Using data from previous studies, we show that we can
detect patterns that other methods miss and that researchers can modify, as needed, thresholds of
immediate interpretability and develop custom statistics to answer specific research questions.
Conclusion: These methods represent a qualitative advance in the location of recurrent CNA
regions, highlight the relevance of population heterogeneity for definitions of recurrence, and can
facilitate the clustering of samples with respect to patterns of CNA. Ultimately, the methods
developed can become important tools in the search for genomic regions harboring disease-critical
genesFunding provided by Fundación de Investigación Médica Mutua
Madrileña. Publication charges covered by projects CONSOLIDER:
CSD2007-00050 of the Spanish Ministry of Science and Innovation and by
RTIC COMBIOMED RD07/0067/0014 of the Spanish Health Ministr
Viruses exacerbating chronic pulmonary disease: the role of immune modulation
Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future. Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications
Susceptibility to type 2 diabetes may be modulated by haplotypes in G6PC2, a target of positive selection
Genetic dissection of drought tolerance and recovery potential by quantitative trait locus mapping of a diploid potato population
Expression of programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulator ligand on human respiratory tract epithelial cells and regulation by respiratory syncytial virus and type 1 and 2 cytokines
BACKGROUND: Respiratory syncytial virus (RSV) is associated with wheezing illness, and infections can occur repeatedly throughout life. We hypothesized that RSV infection of respiratory tract epithelial cells up-regulates B7 molecules that regulate memory immune responses and that type 1 and 2 cytokines differentially modulate this induction. METHODS: We used flow-cytometric analysis to investigate programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulatory ligand (ICOS-L) expression on tracheal (NCI-H292), bronchial (BEAS-2B), and alveolar (A549) epithelial cells; regulation of this expression by RSV, interferon (IFN)- gamma , and interleukin (IL)-4; and the effects of IFN-gamma and IL-4 on RSV-induced expression of these molecules. RESULTS: B7-H3 was strongly expressed, PD-L1 and ICOS-L were moderately expressed, and PD-L2 was weakly expressed on unstimulated tracheal, bronchial, and alveolar epithelial cells. RSV infection up-regulated PD-L1, PD-L2, and B7-H3 expression on all cells and ICOS-L expression on bronchial and alveolar epithelial cells. IL-4 treatment alone had no effect, whereas IFN-gamma treatment alone increased PD-L1 and PD-L2 expression on all cells and decreased B7-H3 expression on bronchial and alveolar epithelial cells. On RSV-infected alevolar epithelial cells, IFN-gamma treatment increased PD-L1 and PD-L2 expression and decreased B7-H3 and ICOS-L expression, and IL-4 treatment increased PD-L2 and B7-H3 expression and decreased ICOS-L expression. CONCLUSIONS: Respiratory tract epithelial cells express a wide range of B7 molecules. RSV infection increases their expression, and this expression is differentially regulated by IFN-gamma and IL-4. These processes may be involved in decreasing T cell antiviral immune responses to RSV and in RSV-associated wheezing
Identification of Rare Causal Variants in Sequence-Based Studies: Methods and Applications to VPS13B, a Gene Involved in Cohen Syndrome and Autism
Clostridium difficile in western Romania: unfavourable outcome predictors in a hospital for infectious diseases
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