Natasha A. Karp

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Circadian rhythms are essential to health. Their disruption is associated with metabolic diseases in experimental animals and man. Local metabolic rhythms represent an output of tissue-based circadian clocks. Attempts to define how local metabolism is temporally coordinated have focused on gene expression by defining extensive and divergent "circadian(More)
The International Mouse Phenotyping Consortium (IMPC) web portal ( provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and standardized protocols for the(More)
In quantitative proteomics, the false discovery rate (FDR) can be defined as the number of false positives within statistically significant changes in expression. False positives accumulate during the simultaneous testing of expression changes across hundreds or thousands of protein or peptide species when univariate tests such as the Student's t test are(More)
MOTIVATION Two-dimensional Difference Gel Electrophoresis (DIGE) measures expression differences for thousands of proteins in parallel. In contrast to DNA microarray analysis, however, there have been few systematic studies on the validity of differential protein expression analysis, and the effects of normalization methods have not yet been investigated.(More)
If biological questions are to be answered using quantitative proteomics, it is essential to design experiments which have sufficient power to be able to detect changes in expression. Sample subpooling is a strategy that can be used to reduce the variance but still allow studies to encompass biological variation. Underlying sample pooling strategies is the(More)
Two-dimensional difference gel electrophoresis (DIGE) is a tool for measuring changes in protein expression between samples involving pre-electrophoretic labeling with cyanine dyes. Here we assess a common method to analyze DIGE data using the DeCyder software system. Experimental error was studied by a series of same sample comparisons. Aliquots of sample(More)
The central circadian pacemaker of the suprachiasmatic nucleus (SCN) is characterized as a series of transcriptional/posttranslational feedback loops. How this molecular mechanism coordinates daily rhythms in the SCN and hence the organism is poorly understood. We conducted the first systematic exploration of the "circadian intracellular proteome" of the(More)
A significant challenge of in-vivo studies is the identification of phenotypes with a method that is robust and reliable. The challenge arises from practical issues that lead to experimental designs which are not ideal. Breeding issues, particularly in the presence of fertility or fecundity problems, frequently lead to data being collected in multiple(More)
Scientists aspire to measure cause and effect. Unfortunately confounding variables, ones that are associated with both the probable cause and the outcome, can lead to an association that is true but potentially misleading. For example, altered body weight is often observed in a gene knockout; however, many other variables, such as lean mass, will also(More)
To further the functional annotation of the mammalian genome, the Sanger Mouse Genetics Programme aims to generate and characterise knockout mice in a high-throughput manner. Annually, approximately 200 lines of knockout mice will be characterised using a standardised battery of phenotyping tests covering key disease indications ranging from obesity to(More)