  Due to rapid technological advances, a wide range of different measurements
can be obtained from a given biological sample including single nucleotide
polymorphisms, copy number variation, gene expression levels, DNA methylation
and proteomic profiles. Each of these distinct measurements provides the means
to characterize a certain aspect of biological diversity, and a fundamental
problem of broad interest concerns the discovery of shared patterns of
variation across different data types. Such data types are heterogeneous in the
sense that they represent measurements taken at very different scales or
described by very different data structures. We propose a distance-based
statistical test, the generalized RV (GRV) test, to assess whether there is a
common and non-random pattern of variability between paired biological
measurements obtained from the same random sample. The measurements enter the
test through distance measures which can be chosen to capture particular
aspects of the data. An approximate null distribution is proposed to compute
p-values in closed-form and without the need to perform costly Monte Carlo
permutation procedures. Compared to the classical Mantel test for association
between distance matrices, the GRV test has been found to be more powerful in a
number of simulation settings. We also report on an application of the GRV test
to detect biological pathways in which genetic variability is associated to
variation in gene expression levels in ovarian cancer samples, and present
results obtained from two independent cohorts.
