SWATH-MS for metabolomics and lipidomics: critical aspects of qualitative and quantitative analysis.

Introduction: While liquid chromatography coupled to mass spectrometric detection in the selected reaction monitoring detection mode offers the best quantification sensitivity for omics, the number of target analytes is limited, must be predefined and specific methods developed. Data independent acquisition (DIA), including SWATH using quadrupole time of flight or orbitrap mass spectrometers and generic acquisition methods, has emerged as a powerful alternative technique for quantitative and qualitative analyses since it can cover a wide range of analytes without predefinition.

Objectives: Here we review the current state of DIA, SWATH-MS and highlight novel acquisition strategies for metabolomics and lipidomics and opportunities for data analysis tools.

Method: Different databases were searched for papers that report developments and applications of DIA and in particular SWATH-MS in metabolomics and lipidomics.

Results: DIA methods generate digital sample records that can be mined retrospectively as further knowledge is gained and, with standardized acquisition schemes, used in multiple studies. The different chemical spaces of metabolites and lipids require different specificities, hence different acquisition and data processing approaches must be considered for their analysis.

Conclusions: Although the hardware and acquisition modes are well defined for SWATH-MS, a major challenge for routine use remains the lack of appropriate software tools capable of handling large datasets and large numbers of analytes.