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Enhancing reproducibility in cancer drug screening: how do we move forward?

ABSTRACT: Large-scale pharmacogenomic high-throughput screening (HTS) studies hold great potential for generating robust genomic predictors of drug response. Two recent large-scale HTS studies have reported results of such screens, revealing several known and novel drug sensitivities and biomarkers. Subsequent evaluation, however, found only moderate interlaboratory concordance in the drug response phenotypes, possibly due to differences in the experimental protocols used in the two studies. This highlights the need for community-wide implementation of standardized assays for measuring drug response phenotypes so that the full potential of HTS is realized. We suggest that the path forward is to establish best practices and standardization of the critical steps in these assays through a collective effort to ensure that the data produced from large-scale screens would not only be of high intrastudy consistency, so that they could be replicated and compared successfully across multiple laboratories.

SUBMITTER: Hatzis C

PROVIDER: S-EPMC4119520 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Enhancing reproducibility in cancer drug screening: how do we move forward?

Hatzis Christos C Bedard Philippe L PL Birkbak Nicolai J NJ Beck Andrew H AH Aerts Hugo J W L HJ Stem David F DF Shi Leming L Clarke Robert R Quackenbush John J Haibe-Kains Benjamin B

Cancer research 20140711 15

Large-scale pharmacogenomic high-throughput screening (HTS) studies hold great potential for generating robust genomic predictors of drug response. Two recent large-scale HTS studies have reported results of such screens, revealing several known and novel drug sensitivities and biomarkers. Subsequent evaluation, however, found only moderate interlaboratory concordance in the drug response phenotypes, possibly due to differences in the experimental protocols used in the two studies. This highligh ...[more]

PMID: 25015668

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Project description:Monitoring fish assemblages is needed to assess whether Marine Protected Areas (MPAs) are meeting their conservation and fisheries management goals, as it allows one to track the progress of recovery of exploited species and associated communities. Underwater Visual Census techniques (UVC) are used to monitor fish assemblages in MPAs. UVCs should be adapted to fish abundance, body-size and behaviour, which can strongly affect fish detectability. In Mediterranean subtidal habitats, however, UVC strip transects of one surface area (25x5 m2) are commonly used to survey the whole fish assemblage, from large shy fish to small crypto-benthic fish. Most high trophic level predators (HTLPs) are large shy fish which rarely swim close to divers and, consequently, their abundance may be under-estimated with commonly used transects. Here, we propose an improvement to traditional transect surveys to better account for differences in behaviour among and within species. First, we compared the effectiveness of combining two transect surface areas (large: 35x20 m2; medium: 25x5 m2) in quantifying large, shy fish within and outside Mediterranean MPAs. We identified species-specific body-size thresholds defining a smaller and a larger size class better sampled by medium and large transects respectively. Combining large and medium transects provided more accurate biomass and species richness estimates for large, shy species than using medium transects alone. We thus combined the new approach with two other transect surface areas commonly used to survey crypto-benthic (10x1 m2) and necto-benthic (25x5 m2) species in order to assess how effectively MPAs protection the whole fish assemblage. We verified that MPAs offer significant protection for HTLPs, their response in terms of biomass and density increase in MPAs was always higher in magnitude than other functional groups. Inside MPAs, the contribution of HTLP reached >25% of total fish biomass, against < 2% outside MPAs. Surveys with multiple transect surface areas allow for a more realistic assessment of the structure of the whole fish assemblage and better assessment of potential recovery of HTLPs within reserves of HTLP.

Dataset Information

Enhancing reproducibility in cancer drug screening: how do we move forward?

Publications

Enhancing reproducibility in cancer drug screening: how do we move forward?

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