Challenges and opportunities for prevention and removal of unwanted variation in lipidomic studies

Large 'omics studies are of particular interest to population and clinical research as they allow elucidation of biological pathways that are often out of reach of other methodologies. Typically, these information rich datasets are produced from multiple coordinated profiling studies that may include lipidomics, metabolomics, proteomics or other strategies to generate high dimensional data. In lipidomics, the generation of such data presents a series of unique technological and logistical challenges; to maximize the power (number of samples) and coverage (number of analytes) of the dataset while minimizing the sources of unwanted variation. Technological advances in analytical platforms, as well as computational approaches, have led to improvement of data quality - especially with regard to instrumental variation. In the small scale, it is possible to control systematic bias from beginning to end. However, as the size and complexity of datasets grow, it is inevitable that unwanted variation arises from multiple sources, some potentially unknown and out of the investigators control. Increases in cohort size and complexity have led to new challenges in sample collection, handling, storage, and preparation. If not considered and dealt with appropriately, this unwanted variation may undermine the quality of the data and reliability of any subsequent analysis. Here we review the various experimental phases where unwanted variation may be introduced and review general strategies and approaches to handle this variation, specifically addressing issues relevant to lipidomics studies.