Murphy E A
Environ Health Perspect. 1981 Dec;42:127-36. doi: 10.1289/ehp.8142127.
The fundamental problems in population monitoring for genetic effects are twofold: the binomialized nature of the data and the lower power due to small risk of finding positive results. The binomial character is artificial, even forced, and can with advantage be replaced by more refined analysis, and by a focus on all mutations, not merely harmful ones. Moreover, a binomial treatment ignores accessory information (birth order, clustering, etc.). But this objective requires that an explicit model be used instead of nonparametric methods; a cancer may represent multiple independent hits that should be separately scored; sequencing of a codon or its product may show multiple distinct changes.
数据的二项式性质以及由于发现阳性结果的风险较小而导致的检验效能较低。二项式特征是人为的，甚至是强制的，可以通过更精细的分析以及关注所有突变（而不仅仅是有害突变）来加以改进。此外，二项式处理忽略了辅助信息（出生顺序、聚集等）。但这一目标要求使用明确的模型而非非参数方法；癌症可能代表多个独立的致病变异，应分别计分；密码子或其产物的测序可能显示多个不同的变化。
