Targeted realignment of LC-MS profiles by neighbor-wise compound-specific graphical time warping with misalignment detection

Chiung-Ting Wu, Yizhi Wang, Yinxue Wang, Timothy M. D. Ebbels, Ibrahim Karaman, Gonçalo Graça, Rui Pinto, David M. Herrington, Yue Wang, Guoqiang Yu

Abstract: Liquid chromatography–mass spectrometry (LC-MS) is a standard method for proteomics and metabolomics analysis of biological samples. Unfortunately, it suffers from various changes in the retention times (RT) of the same compound in different samples, and these must be subsequently corrected (aligned) during data processing. Classic alignment methods such as in the popular XCMS package often assume a single time-warping function for each sample. Thus, the potentially varying RT drift for compounds with different masses in a sample is neglected in these methods. Moreover, the systematic change in RT drift across run order is often not considered by alignment algorithms. Therefore, these methods cannot effectively correct all misalignments. For a large-scale experiment involving many samples, the existence of misalignment becomes inevitable and concerning.