Biomedical subjects

Per Broberg

Publications and source records attributed to Per Broberg.

3 recordsLinked to original sources

PubMed2003

Statistical methods for ranking differentially expressed genes.

In the analysis of microarray data the identification of differential expression is paramount. Here I outline a method for finding an optimal test statistic with which to rank genes with respect to differential expression. Tests of the method show that it allows generation of top gene lists that give few false positives and few false negatives. Estimation of the false-negative as well as the false-positive rate lies at the heart of the method.

Computational Biology↗

PubMed2002

Ranking genes with respect to differential expression.

BACKGROUND: In the pharmaceutical industry and in academia substantial efforts are made to make the best use of the promising microarray technology. The data generated by microarrays are more complex than most other biological data attracting much attention at this point. A method for finding an optimal test statistic with which to rank genes with respect to differential expression is outlined and tested. At the heart of the method lies an estimate of the false negative and false positive rates. Both investing in false positives and missing true positives lead to a waste of resources. The procedure sets out to minimise these errors. For calculation of the false positive and negative rates a simulation procedure is invoked. RESULTS: The method outperforms commonly used alternatives when applied to simulated data modelled after real cDNA array data as well as when applied to real oligonucleotide array data. In both cases the method comes out as the over-all winner. The simulated data are analysed both exponentiated and on the original scale, thus providing evidence of the ability to cope with normal and lognormal distributions. In the case of the real life data it is shown that the proposed method will tend to push the differentially expressed genes higher up on a test statistic based ranking list than the competitors. CONCLUSIONS: The approach of making use of information concerning both the false positive and false negative rates in the inference adds a useful tool to the toolbox available to scientists in functional genomics.

Gene Expression Profiling↗

PubMed2002

Natural allergen exposure does not diminish the sensitivity of cytokine production to glucocorticosteroids in blood cells of seasonal allergic asthma and rhinitis patients.

Glucocorticosteroid (GCS) inhibition of cytokine production is a major anti-inflammatory mechanism. However, increased production of pro-inflammatory cytokines during allergic airway inflammation has been proposed to reduce GCS effects. This study aimed to investigate whether allergic airway inflammation due to natural allergen exposure might decrease the sensitivity of granulocyte-macrophage colony-stimulating factor (GM-CSF) production to GCS in blood cells. Blood samples were collected from patients with seasonal allergic asthma (n = 10) and rhinitis (n = 8) and healthy subjects (n = 9), before, during, and after the birch pollen season. Whole blood cultures were stimulated with LPS (10 ng/ml) and treated with budesonide (10(-11)-10(-7) M) for 20 h. GM-CSF levels were analysed using immunoassay. Birch pollen exposure did not alter LPS-stimulated GM-CSF production, although disease symptoms and blood eosinophils increased in the patients. There were no significant differences in budesonide inhibition of GM-CSF production by blood cells of asthma and rhinitis patients compared with cells of healthy subjects before, during or after the birch pollen season and no change in response to allergen exposure. A concentration of 1 nM budesonide inhibited GM-CSF production by more than 50% at all time points. In conclusion, natural allergen exposure did not reduce the sensitivity of GM-CSF production to GCS inhibition in blood cells of seasonal allergic asthma and rhinitis patients.

Adult↗