Quality assessment and interference detection in targeted mass spectrometry data using machine learning.

Advances in the field of targeted proteomics and mass spectrometry have significantly improved assay sensitivity and multiplexing capacity. The high-throughput nature of targeted proteomics experiments has increased the rate of data production, which requires development of novel analytical tools to keep up with data processing demand. Currently, development and validation of targeted mass spectrometry assays require manual inspection of chromatographic peaks from large datasets to ensure quality, a process that is time consuming, prone to inter- and intra-operator variability and limits the efficiency of data interpretation from targeted proteomics analyses. To address this challenge, we have developed TargetedMSQC, an R package that facilitates quality control and verification of chromatographic peaks from targeted proteomics datasets. This tool calculates metrics to quantify several quality aspects of a chromatographic peak, e.g. symmetry, jaggedness and modality, co-elution and shape similarity of monitored transitions in a peak group, as well as the consistency of transitions' ratios between endogenous analytes and isotopically labeled internal standards and consistency of retention time across multiple runs. The algorithm takes advantage of supervised machine learning to identify peaks with interference or poor chromatography based on a set of peaks that have been annotated by an expert analyst. Using TargetedMSQC to analyze targeted proteomics data reduces the time spent on manual inspection of peaks and improves both speed and accuracy of interference detection. Additionally, by allowing the analysts to customize the tool for application on different datasets, TargetedMSQC gives the users the flexibility to define the acceptable quality for specific datasets. Furthermore, automated and quantitative assessment of peak quality offers a more objective and systematic framework for high throughput analysis of targeted mass spectrometry assay datasets and is a step towards more robust and faster assay implementation.