The coefficient of variation (CV) is often used in proteomics as a proxy to characterize the performance of a quantitation method and/or the related software. In this note, we question the excessive reliance on this metric in quantitative proteomics that may result in erroneous conclusions. We support this note using a ground‐truth Human‐Yeast‐E. coli dataset demonstrating in a number of cases that erroneous data processing methods may lead to a low CV which has nothing to do with these methods’ performances in quantitation.

One of the key steps in data dependent acquisition (DDA) proteomics is detection of peptide isotopic clusters, also called "features", in MS1 spectra and matching them to MS/MS-based peptide identifications. A number of peptide feature detection tools became available in recent years each relying on its own matching algorithm. Here, we provide an integrated solution, Intensity-based Quantitative Mix and Match Approach (IQMMA), which integrates a number of peptide feature detection algorithms and returns the most probable intensity values for the MS/MS-based identifications. IQMMA was tested using available proteomic data acquired for both well-characterized (ground truth) and real-world biological samples, including a mix of E. coli digest spiked at different concentrations into the HeLa digest used as a background and a set of glioblastoma cell lines. Three open-source feature detection algorithms were integrated: Dinosaur, biosaur2 and OpenMS FeatureFinder. Neither of them was found optimal when applied individually to all the datasets employed in this work, however, their combined use in IQMMA improved efficiency of subsequent protein quantitation. The software implementing IQMMA is freely available at https://github.com/PostoenkoVI/IQMMA under Apache 2.0 license.