@article{HiortSchlaffnerSteenetal.2022,
  author    = {Hiort, Pauline and Schlaffner, Christoph N. and Steen, Judith A. and Renard, Bernhard Y. and Steen, Hanno},
  title     = {multiFLEX-LF: a computational approach to quantify the modification stoichiometries in label-free proteomics data sets},
  series = {Journal of proteome research},
  volume    = {21},
  journal   = {Journal of proteome research},
  number    = {4},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1535-3893},
  doi       = {10.1021/acs.jproteome.1c00669},
  pages     = {899 -- 909},
  year      = {2022},
  abstract  = {In liquid-chromatography-tandem-mass-spectrometry-based proteomics, information about the presence and stoichiometry ofprotein modifications is not readily available. To overcome this problem,we developed multiFLEX-LF, a computational tool that builds uponFLEXIQuant, which detects modified peptide precursors and quantifiestheir modification extent by monitoring the differences between observedand expected intensities of the unmodified precursors. multiFLEX-LFrelies on robust linear regression to calculate the modification extent of agiven precursor relative to a within-study reference. multiFLEX-LF cananalyze entire label-free discovery proteomics data sets in a precursor-centric manner without preselecting a protein of interest. To analyzemodification dynamics and coregulated modifications, we hierarchicallyclustered the precursors of all proteins based on their computed relativemodification scores. We applied multiFLEX-LF to a data-independent-acquisition-based data set acquired using the anaphase-promoting complex/cyclosome (APC/C) isolated at various time pointsduring mitosis. The clustering of the precursors allows for identifying varying modification dynamics and ordering the modificationevents. Overall, multiFLEX-LF enables the fast identification of potentially differentially modified peptide precursors and thequantification of their differential modification extent in large data sets using a personal computer. Additionally, multiFLEX-LF candrive the large-scale investigation of the modification dynamics of peptide precursors in time-series and case-control studies.multiFLEX-LF is available athttps://gitlab.com/SteenOmicsLab/multiflex-lf.},
  language  = {en}
}