Biology subjects

Hutchison, A. L.

Publications and source records attributed to Hutchison, A. L..

3 recordsLinked to original sources

bioRxiv2023

Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity in Drosophila

Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor Clock is crucial for a robust longevity and fecundity response to DR in Drosophila. To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets. In contrast to more chronic DR regimens, we did not detect significant changes in the rhythmic expression of core clock genes. Yet we discovered that DR induced de novo rhythmicity or increased expression of rhythmic clock output genes. Network analysis revealed that DR increased network connectivity in one module comprised of genes encoding proteasome subunits. Adult, fat body specific RNAi knockdown demonstrated that proteasome subunits contribute to DR-mediated lifespan extension. Thus, clock control of output links DR-mediated changes in rhythmic transcription to lifespan extension.

genetics↗

bioRxiv2017

Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data

MotivationThere is much interest in using genome-wide expression time series to identify circadian genes. However, the cost and effort of such measurements often limits data collection. Consequently, it is difficult to assess the experimental uncertainty in the measurements and, in turn, to detect periodic patterns with statistical confidence.\n\nResultsWe show that parametric bootstrapping and empirical Bayes methods for variance shrinkage can improve rhythm detection in genome-wide expression time series. We demonstrate these approaches by building on the empirical JTK_CYCLE method (eJTK) to formulate a method that we term BooteJTK. Our procedure rapidly and accurately detects cycling time series by combining information about measurement uncertainty with information about the rank order of the time series values. We exploit a publicly available genome-wide dataset with high time resolution to show that BooteJTK provides more consistent rhythm detection thanexisting methods at typical sampling frequencies. Then, we apply BooteJTK to genome-wide expression time series from multiple tissues and show that it reveals biologically sensible tissue relationships that eJTK misses.\n\nAvailabilityBootstrap eJTK (BooteJTK) is implemented in Python and is freely available on GitHub at https://github.com/alanlhutchison/BooteJTK.

bioinformatics↗

bioRxiv2017

Correcting for Dependent P-values in Rhythm Detection

There is much interest in using genome-wide expression time series to identify circadian genes. Several methods have been developed to test for rhythmicity in sparsely sampled time series typical of such measurements. Because these methods are statistical in nature, they rely on estimating the probabilities that patterns arise by chance (i.e., p-values). Here we show that leading methods implicitly make inappropriate assumptions of independence when estimating p-values. We show how to correct for the dependence to obtain accurate estimates for statistical significance during rhythm detection.

bioinformatics↗