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TGFbeta ligands act as tumor suppressors in early stage tumors but are paradoxically diverted into potent prometastatic factors in advanced cancers. The molecular nature of this switch remains enigmatic. Here, we show that TGFbeta-dependent cell migration, invasion and metastasis are empowered by mutant-p53 and opposed by p63. Mechanistically, TGFbeta acts(More)
Cells respond to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) by orchestrating events that coordinate cell cycle progression and DNA repair. How cells signal and repair DSBs is not yet fully understood. A genome-wide RNA interference screen in Caenorhabditis elegans identified egr-1 as a factor that protects worm cells against IR. The(More)
This paper presents an overview of the current state of the art in multiple testing in genomics data from a user's perspective. We describe methods for familywise error control, false discovery rate control and false discovery proportion estimation and confidence, both conceptually and practically, and explain when to use which type of error rate. We(More)
SUMMARY Many assessment instruments used in the evaluation of toxicity, safety, pain, or disease progression consider multiple ordinal endpoints to fully capture the presence and severity of treatment effects. Contingency tables underlying these correlated responses are often sparse and imbalanced, rendering asymptotic results unreliable or model fitting(More)
Earlier studies of the tRNA processing enzyme, tRNA nucleotidyltransferase, in rat liver cells suggested that the enzyme was absent from nuclei, whereas more recent studies with tRNA transcription-processing systems from Xenopus laevis oocytes indicated that the enzyme was present in germinal vesicles of these cells. In order to resolve this apparent(More)
The integration of high-throughput genomic data represents an opportunity for deciphering the interplay between structural and functional organization of genomes and for discovering novel biomarkers. However, the development of integrative approaches to complement gene expression (GE) data with other types of gene information, such as copy number (CN) and(More)
We propose three-sided testing, a testing framework for simultaneous testing of inferiority, equivalence and superiority in clinical trials, controlling for multiple testing using the partitioning principle. Like the usual two-sided testing approach, this approach is completely symmetric in the two treatments compared. Still, because the hypotheses of(More)
When fitting generalized linear models or the Cox proportional hazards model, it is important to have tools to test for lack of fit. Because lack of fit comes in all shapes and sizes, distinguishing among different types of lack of fit is of practical importance. We argue that an adequate diagnosis of lack of fit requires a specified alternative model. Such(More)
SUMMARY Chromosomal patterns of genomic signals represent molecular fingerprints that may reveal how the local structural organization of a genome impacts the functional control mechanisms. Thus, the integrative analysis of multiple sources of genomic data and information deepens the resolution and enhances the interpretation of stand-alone high-throughput(More)