Tests for comparison of multiple endpoints with application to omics data

In biomedical research, multiple endpoints are commonly analyzed in “omics” fields like genomics, proteomics and metabolomics. Traditional methods designed for low-dimensional data either perform poorly or are not applicable when analyzing high-dimensional data whose dimension is generally similar to, or even much larger than, the number of subjects. The complex biochemical interplay between hundreds (or thousands) of endpoints is reflected by complex dependence relations. The aim of the paper is to propose tests that are very suitable for analyzing omics data because they do not require the normality assumption, are powerful also for small sample sizes, in the presence of complex dependence relations among endpoints, and when the number of endpoints is much larger than the number of subjects. Unbiasedness and consistency of the tests are proved and their size and power are assessed numerically. It is shown that the proposed approach based on the nonparametric combination of dependent interpoint distance tests is very effective. Applications to genomics and metabolomics are discussed.

The limit distribution of the largest interpoint distance for distributions supported by a d-dimensional ellipsoid and generalizations

We study the asymptotic behaviour of the maximum interpoint distance of random points in a d-dimensional ellipsoid with a unique major axis. Instead of investigating only a fixed number of n points as n tends to ∞, we consider the much more general setting in which the random points are the supports of appropriately defined Poisson processes. Our main result covers the case of uniformly distributed points.

Multivariate tests based on interpoint distances with application to magnetic resonance imaging

The multivariate location problem is addressed. The most familiar method to address the problem is the Hotelling test. When the hypothesis of normal distributions holds, the Hotelling test is optimal. Unfortunately, in practice the distributions underlying the samples are generally unknown and without assuming normality the finite sample unbiasedness of the Hotelling test is not guaranteed. Moreover, high-dimensional data are increasingly encountered when analyzing medical and biological problems, and in these situations the Hotelling test performs poorly or cannot be computed. A test that is unbiased for non-normal data, for small sample sizes as well as for two-sided alternatives and that can be computed for high-dimensional data has been recently proposed and is based on the ranks of the interpoint Euclidean distances between observations. Five modifications of this test are proposed and compared to the original test and the Hotelling test. Unbiasedness and consistency of the tests are proven and the problem of power computation is addressed. It is shown that two of the modified interpoint distance-based tests are always more powerful than the original test. Particularly, the modified test based on the Tippett criterium is suggested when the assumption of normality is not tenable and/or in case of high-dimensional data with complex dependence structure which are typical in molecular biology and medical imaging. A practical application to a case-control study where functional magnetic resonance imaging is used is discussed.