Biomedical subjects

Jochen Jaeger

Publications and source records attributed to Jochen Jaeger.

3 recordsLinked to original sources

PubMed2006

Selecting normalization genes for small diagnostic microarrays.

BACKGROUND: Normalization of gene expression microarrays carrying thousands of genes is based on assumptions that do not hold for diagnostic microarrays carrying only few genes. Thus, applying standard microarray normalization strategies to diagnostic microarrays causes new normalization problems. RESULTS: In this paper we point out the differences of normalizing large microarrays and small diagnostic microarrays. We suggest to include additional normalization genes on the small diagnostic microarrays and propose two strategies for selecting them from genomewide microarray studies. The first is a data driven univariate selection of normalization genes. The second is multivariate and based on finding a balanced diagnostic signature. Finally, we compare both methods to standard normalization protocols known from large microarrays. CONCLUSION: Not including additional genes for normalization on small microarrays leads to a loss of diagnostic information. Using house keeping genes from the literature for normalization fails to work for certain datasets. While a data driven selection of additional normalization genes works well, the best results were obtained using a balanced signature.

Algorithms↗

PubMed2005

Early diagnostic marker panel determination for microarray based clinical studies.

We present a novel, cost efficient two-phase design for predictive clinical gene expression studies: early marker panel determination (EMPD). In Phase-1, genome-wide microarrays are used only for a small number of individual patient samples. From this Phase-1 data a panel of marker genes is derived. In Phase-2, the expression values of these marker panel genes are measured for a large group of patients and a predictive classification model is learned from this data. Phase-2 does not require the use of expensive whole genome microarrays, thus making EMPD a cost efficient alternative for current trials. The expected performance loss of EMPD is compared to designs which use genome-wide microarrays for all patients. We also examine the trade-off between the number of patients included in Phase-1 and the number of marker genes required in Phase-2. By analysis of five published datasets we find that in Phase-1 already 16 patients per group are sufficient to determine a suitable marker panel of 10 genes, and that this early decision compromises the final performance only marginally.

Journal Article↗

PubMed2004

Atherosclerotic plaque smooth muscle cells have a distinct phenotype.

OBJECTIVE: The present study addresses the question, "Are plaque smooth muscles cells (SMCs) genetically distinct from medial SMCs as reflected by the ability to maintain a distinctive expression phenotype in vitro?" METHODS AND RESULTS: Multiple cell strains were developed from carotid endarcterectomy specimens, and quadruplicate array hybridizations were completed for each sample. A new normalization protocol was developed and used to analyze the data. Permutation analysis suggests that most of the significant differences in expression could not have occurred by chance. A broad pattern of significant expression differences, consisting of almost 5% of the genes probed, was detected. Quantitative polymerase chain reaction (QPCR) confirmation was found in 70% of a subset of genes selected for validation. CONCLUSIONS: The SMC cultures were nearly indistinguishable by morphological features, population doubling time, and sensitivity to cell death induced by Fas cross-linking. Surprisingly, array expression analysis identified differences so extensive that we conclude that plaque and medial SMCs are distinctly different SMC cell types.

Apoptosis↗