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A biologist's guide to statistical thinking and analysis.

ABSTRACT: The proper understanding and use of statistical tools are essential to the scientific enterprise. This is true both at the level of designing one's own experiments as well as for critically evaluating studies carried out by others. Unfortunately, many researchers who are otherwise rigorous and thoughtful in their scientific approach lack sufficient knowledge of this field. This methods chapter is written with such individuals in mind. Although the majority of examples are drawn from the field of Caenorhabditis elegans biology, the concepts and practical applications are also relevant to those who work in the disciplines of molecular genetics and cell and developmental biology. Our intent has been to limit theoretical considerations to a necessary minimum and to use common examples as illustrations for statistical analysis. Our chapter includes a description of basic terms and central concepts and also contains in-depth discussions on the analysis of means, proportions, ratios, probabilities, and correlations. We also address issues related to sample size, normality, outliers, and non-parametric approaches.

SUBMITTER: Fay DS

PROVIDER: S-EPMC3880567 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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A biologist's guide to statistical thinking and analysis.

Fay David S DS Gerow Ken K

WormBook : the online review of C. elegans biology 20130709

The proper understanding and use of statistical tools are essential to the scientific enterprise. This is true both at the level of designing one's own experiments as well as for critically evaluating studies carried out by others. Unfortunately, many researchers who are otherwise rigorous and thoughtful in their scientific approach lack sufficient knowledge of this field. This methods chapter is written with such individuals in mind. Although the majority of examples are drawn from the field of ...[more]

PMID: 23908055

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Project description:Aurora kinases are essential for cell division and are frequently misregulated in human cancers. Based on their potential as cancer therapeutics, a plethora of small molecule Aurora kinase inhibitors have been developed, with a subset having been adopted as tools in cell biology. Here, we fill a gap in the characterization of Aurora kinase inhibitors by using biochemical and cell-based assays to systematically profile a panel of 10 commercially available compounds with reported selectivity for Aurora A (MLN8054, MLN8237, MK-5108, MK-8745, Genentech Aurora Inhibitor 1), Aurora B (Hesperadin, ZM447439, AZD1152-HQPA, GSK1070916), or Aurora A/B (VX-680). We quantify the in vitro effect of each inhibitor on the activity of Aurora A alone, as well as Aurora A and Aurora B bound to fragments of their activators, TPX2 and INCENP, respectively. We also report kinome profiling results for a subset of these compounds to highlight potential off-target effects. In a cellular context, we demonstrate that immunofluorescence-based detection of LATS2 and histone H3 phospho-epitopes provides a facile and reliable means to assess potency and specificity of Aurora A versus Aurora B inhibition, and that G2 duration measured in a live imaging assay is a specific readout of Aurora A activity. Our analysis also highlights variation between HeLa, U2OS, and hTERT-RPE1 cells that impacts selective Aurora A inhibition. For Aurora B, all four tested compounds exhibit excellent selectivity and do not significantly inhibit Aurora A at effective doses. For Aurora A, MK-5108 and MK-8745 are significantly more selective than the commonly used inhibitors MLN8054 and MLN8237. A crystal structure of an Aurora A/MK-5108 complex that we determined suggests the chemical basis for this higher specificity. Taken together, our quantitative biochemical and cell-based analyses indicate that AZD1152-HQPA and MK-8745 are the best current tools for selectively inhibiting Aurora B and Aurora A, respectively. However, MK-8745 is not nearly as ideal as AZD1152-HQPA in that it requires high concentrations to achieve full inhibition in a cellular context, indicating a need for more potent Aurora A-selective inhibitors. We conclude with a set of "good practice" guidelines for the use of Aurora inhibitors in cell biology experiments.

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A biologist's guide to statistical thinking and analysis.

Publications

A biologist's guide to statistical thinking and analysis.

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