LandScape: a simple method to aggregate p--Values and other stochastic variables without a priori grouping

TY - JOUR

T1 - LandScape: a simple method to aggregate p--Values and other stochastic variables without a priori grouping

AU - Wiuf, Carsten

AU - Pallesen, Jonatan

AU - Foldager, Leslie

AU - Grove, Jakob

PY - 2016/8

Y1 - 2016/8

N2 - In many areas of science it is custom to perform many, potentially millions, of tests simultaneously. To gain statistical power it is common to group tests based on a priori criteria such as predefined regions or by sliding windows. However, it is not straightforward to choose grouping criteria and the results might depend on the chosen criteria. Methods that summarize, or aggregate, test statistics or p-values, without relying on a priori criteria, are therefore desirable. We present a simple method to aggregate a sequence of stochasticvariables, such as test statistics or p-values, into fewer variables without assuming a priori defined groups. We provide different ways to evaluate the significance of the aggregated variables based on theoretical considerationsand resampling techniques, and show that under certain assumptions the FWER is controlled in the strong sense. Validity of the method was demonstrated using simulations and real data analyses. Our method may be a useful supplement to standard procedures relying on evaluation of test statistics individually. Moreover, by being agnostic and not relying on predefined selected regions, it might be a practical alternative to conventionally used methods of aggregation of p-values over regions. The method is implementedin Python and freely available online (through GitHub, see the Supplementary information).

AB - In many areas of science it is custom to perform many, potentially millions, of tests simultaneously. To gain statistical power it is common to group tests based on a priori criteria such as predefined regions or by sliding windows. However, it is not straightforward to choose grouping criteria and the results might depend on the chosen criteria. Methods that summarize, or aggregate, test statistics or p-values, without relying on a priori criteria, are therefore desirable. We present a simple method to aggregate a sequence of stochasticvariables, such as test statistics or p-values, into fewer variables without assuming a priori defined groups. We provide different ways to evaluate the significance of the aggregated variables based on theoretical considerationsand resampling techniques, and show that under certain assumptions the FWER is controlled in the strong sense. Validity of the method was demonstrated using simulations and real data analyses. Our method may be a useful supplement to standard procedures relying on evaluation of test statistics individually. Moreover, by being agnostic and not relying on predefined selected regions, it might be a practical alternative to conventionally used methods of aggregation of p-values over regions. The method is implementedin Python and freely available online (through GitHub, see the Supplementary information).

KW - association mapping

KW - genome scan

KW - multiple testing

KW - random walk

UR - http://www.scopus.com/inward/record.url?scp=84979730180&partnerID=8YFLogxK

U2 - 10.1515/sagmb-2015-0085

DO - 10.1515/sagmb-2015-0085

M3 - Journal article

C2 - 27269897

SN - 1544-6115

VL - 15

SP - 349

EP - 361

JO - Statistical Applications in Genetics and Molecular Biology

JF - Statistical Applications in Genetics and Molecular Biology

IS - 4

ER -