TY  - JOUR
A1  - Hiort, Pauline
A1  - Schlaffner, Christoph N.
A1  - Steen, Judith A.
A1  - Renard, Bernhard Y.
A1  - Steen, Hanno
T1  - multiFLEX-LF: a computational approach to quantify the modification stoichiometries in label-free proteomics data sets
JF  - Journal of proteome research
N2  - 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.
KW  - bioinformatics tool
KW  - label-free quantification
KW  - LC-MS
KW  - MS
KW  - post-translational modification
KW  - modification stoichiometry
KW  - PTM
KW  - quantification
Y1  - 2022
U6  - https://doi.org/10.1021/acs.jproteome.1c00669
SN  - 1535-3893
SN  - 1535-3907
VL  - 21
IS  - 4
SP  - 899
EP  - 909
PB  - American Chemical Society
CY  - Washington
ER  -