Extraction and integration of genetic networks from short-profile omic datasets

Abstract

Mass-spectrometry technologies are widely used in the fields of ionomics and metabolomics to simultaneously profile at the genome scale intracellular concentrations of e.g. amino acids or elements. Short profiles of molecular or sub-molecular features are intrinsically non-Gaussian and may reveal patterns of correlations that reflect the system nature of the cell biochemistry and biology. Here we introduce two profile similarity measures that enforce information from the empirical covariance matrix of the data, the Mahalanobis cosine and the hybrid-Mahalanobis cosine. We evaluate the performance of these similarity measures in the task of inferring and integrating genetic networks from omics data by analysing experimental datasets derived from the ionome and the metabolome of the model organism S. cerevisiae, and several large curated databases of genetic annotations. The proposed covariance-based similarity measures can in general recover known and predicted associations between genes better than the commonly used Pearson's correlation and the standard cosine similarity. The choice of which of the two measures to recommend depends upon whether the focus is on extracting genetic associations at a global or local genetic network scale.