3,169 research outputs found
A Bayesian measurement error model for two-channel cell-based RNAi data with replicates
RNA interference (RNAi) is an endogenous cellular process in which small
double-stranded RNAs lead to the destruction of mRNAs with complementary
nucleoside sequence. With the production of RNAi libraries, large-scale RNAi
screening in human cells can be conducted to identify unknown genes involved in
a biological pathway. One challenge researchers face is how to deal with the
multiple testing issue and the related false positive rate (FDR) and false
negative rate (FNR). This paper proposes a Bayesian hierarchical measurement
error model for the analysis of data from a two-channel RNAi high-throughput
experiment with replicates, in which both the activity of a particular
biological pathway and cell viability are monitored and the goal is to identify
short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting
cell activity. Simulation studies demonstrate the flexibility and robustness of
the Bayesian method and the benefits of having replicates in the experiment.
This method is illustrated through analyzing the data from a RNAi
high-throughput screening that searches for cellular factors affecting HCV
replication without affecting cell viability; comparisons of the results from
this HCV study and some of those reported in the literature are included.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS496 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure
Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats
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