52 research outputs found
Improved quality control processing of peptide-centric LC-MS proteomics data
Motivation: In the analysis of differential peptide peak intensities (i.e. abundance measures), LC-MS analyses with poor quality peptide abundance data can bias downstream statistical analyses and hence the biological interpretation for an otherwise high-quality dataset. Although considerable effort has been placed on assuring the quality of the peptide identification with respect to spectral processing, to date quality assessment of the subsequent peptide abundance data matrix has been limited to a subjective visual inspection of run-by-run correlation or individual peptide components. Identifying statistical outliers is a critical step in the processing of proteomics data as many of the downstream statistical analyses [e.g. analysis of variance (ANOVA)] rely upon accurate estimates of sample variance, and their results are influenced by extreme values
Biological Interactions and Dynamics Science Theme Advisory Panel (BID-STAP)
This report contains the charge to the panel, the panel's discussions and panel recommendations
ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for <it>in vitro </it>toxicity studies
<p>Abstract</p> <p>Background</p> <p>The difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment, particularly for <it>in vitro </it>systems. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. Ī¼g particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion).</p> <p>Results</p> <p>The <it>In vitro </it>Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular doses for multiple sizes of polystyrene spheres (20-1100 nm), 35 nm amorphous silica, and large agglomerates of 30 nm iron oxide particles. Overall, without adjusting any parameters, model predicted cellular doses were in close agreement with the experimental data, differing from as little as 5% to as much as three-fold, but in most cases approximately two-fold, within the limits of the accuracy of the measurement systems. Applying the model, we generalize the effects of particle size, particle density, agglomeration state and agglomerate characteristics on target cell dosimetry <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our results confirm our hypothesis that for liquid-based <it>in vitro </it>systems, the dose-rates and target cell doses for all particles are not equal; they can vary significantly, in direct contrast to the assumption of dose-equivalency implicit in the use of mass-based media concentrations as metrics of exposure for dose-response assessment. The difference between equivalent nominal media concentration exposures on a Ī¼g/mL basis and target cell doses on a particle surface area or number basis can be as high as three to six orders of magnitude. As a consequence, <it>in vitro </it>hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for <it>in vitro </it>nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually, an adjunct to such measurements.</p
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