Search PubMed⌕ Search

PubMed · 10832919

Analyzing bioassay data using Bayesian methods--a primer.

Abstract

The classical statistics approach used in health physics for the interpretation of measurements is deficient in that it does not take into account "needle in a haystack" effects, that is, correct identification of events that are rare in a population. This is often the case in health physics measurements, and the false positive fraction (the fraction of results measuring positive that are actually zero) is often very large using the prescriptions of classical statistics. Bayesian statistics provides a methodology to minimize the number of incorrect decisions (wrong calls): false positives and false negatives. We present the basic method and a heuristic discussion. Examples are given using numerically generated and real bioassay data for tritium. Various analytical models are used to fit the prior probability distribution in order to test the sensitivity to choice of model. Parametric studies show that for typical situations involving rare events the normalized Bayesian decision level k(alpha) = Lc/sigma0, where sigma0 is the measurement uncertainty for zero true amount, is in the range of 3 to 5 depending on the true positive rate. Four times sigma0 rather than approximately two times sigma0, as in classical statistics, would seem a better choice for the decision level in these situations.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

G Miller, W C Inkret, M E Schillaci, H F Martz, T T Little. 2000. Analyzing bioassay data using Bayesian methods--a primer.. https://doi.org/10.1097/00004032-200006000-00002

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions.

The nuclear-encoded Sup35p protein is responsible for the prion-like [PSI(+)] determinant of yeast, with Sup35p existing largely as a high molecular weight aggregate in [PSI(+)] strains. Here we show that the five oligopeptide repeats present at the N-terminus of Sup35p are responsible for stabilizing aggregation of Sup35p in vivo. Sequential deletion of the oligopeptide repeats prevented the maintenance of [PSI(+)] by the truncated Sup35p, although deletants containing only two repeats could be incorporated into pre-existing aggregates of wild-type Sup35p. The mammalian prion protein PrP also contains similar oligopeptide repeats and we show here that a human PrP repeat (PHGGGWGQ) is able functionally to replace a Sup35p oligopeptide repeat to allow stable [PSI(+)] propagation in vivo. Our data suggest a model in which the oligopeptide repeats in Sup35p stabilize intermolecular interactions between Sup35p proteins that initiate establishment of the aggregated state. Modulating repeat number therefore alters the rate of yeast prion conversion in vivo. Furthermore, there appears to be evolutionary conservation of function of the N-terminally located oligopeptide repeats in prion propagation.

Biological Assay↗

Subtle alterations in growth medium composition can dramatically alter the percentage of unsaturated fatty acids in the yeast Saccharomyces cerevisiae.

The essence of the scientific method is the production of reproducible results in repeated experiments. Cells of the yeast strain DBY747 normally contain 36% unsaturated fatty acids but suddenly, and initially inexplicably, lipid analysis revealed 72% unsaturated fatty acids in the same strain at the same growth temperature. A comparative lipid analysis of DBY747 grown in YEPD and in a number of different types and batches of Yeast Nitrogen Base media revealed two heretofore unreported phenomena. We provide mass spectroscopy and yeast bioassay evidence suggesting that the increase in lipid unsaturation can be attributed to the presence of the plasticizing agent dioctylphthalate in YNB and bactopeptone packaged in 'new' plastic containers first introduced by Difco some 3-4 years ago. We also demonstrate that L-methionine plays an important role in determining the percentage of unsaturated fatty acids in cells grown in laboratory-produced YNB. The results illustrate a novel aspect of methionine metabolism while at the same time highlighting the need for more stringent control to be exercised by the companies that formulate and package defined media.

Biological Assay↗

Safety testing for replication-competent retrovirus associated with gibbon ape leukemia virus-pseudotyped retroviral vectors.

The potential pathogenicity of replication-competent retroviruses (RCR) requires vigilant testing to exclude inadvertent contamination of clinical gene therapy vector products with RCR. Pseudotyped vectors using the gibbon ape leukemia virus (GALV) envelope have entered into clinical trials but specific recommendations regarding methods for screening of vector product and analysis of clinical samples have not been set forth. Unfortunately, current screening assays used for detecting amphotropic RCR are not suitable for GALV-pseudotyped RCR. We modified the extended S+/L- assay for RCR detection by using human 293 cells for virus amplification. Of five cell lines tested, 293 cells were selected because they combined a high transduction efficiency and an ability to generate RCR at high titer. After optimizing the amplification assay, a dilution of GALV virus could consistently be detected at a dilution of 10(-6). In coculture experiments, one GALV-infected cell could be consistently detected in 10(6) uninfected cells. A PCR-based assay was developed that was capable of detecting 100 copies of a GALV envelope containing plasmid diluted in 1 microg of DNA obtained from uninfected cells. PCR was also able to detect one GALV-infected cell in 10(6) uninfected cells. These assays will be suitable for testing of vector preparations and for monitoring of clinical samples from patients treated in clinical gene therapy protocols. The assays developed are similar in methodology and sensitivity to those currently used for certification of amphotropic retroviral vectors.

Biological Assay↗