Please cite this article in press as: E.M. Solovyeva, et al., Semi-supervised quality control method for proteome analyses based on tandem mass spectrometry, Int. J. Mass Spectrom. (2017), http://dx.doi.org/10.1016/j.ijms.2017.09.008 ARTICLE IN PRESS G Model MASPEC-15871; No. of Pages 6 International Journal of Mass Spectrometry xxx (2017) xxx–xxx Contents lists available at ScienceDirect International Journal of Mass Spectrometry jou rn al h om epage: www.elsevier.com/locate/ijms Full Length Article Semi-supervised quality control method for proteome analyses based on tandem mass spectrometry Elizaveta M. Solovyeva a,b , Anna A. Lobas a,b , Arthur T. Kopylov c , Mikhail V. Gorshkov a,b,* a Moscow Institute of Physics and Technology (State University), Moscow Region, Dolgoprudny, 141701, Russia b V.L.Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia c Institute of Biomedical Chemistry, Moscow, 119121, Russia a r t i c l e i n f o Article history: Received 30 March 2017 Received in revised form 6 September 2017 Accepted 15 September 2017 Available online xxx Keywords: Proteomics Mass spectrometry Experiment quality control a b s t r a c t With the increasing volume of bottom-up proteome analyses using liquid chromatography/mass spectrometry (LC–MS), a rapid and easy for interpretation assessment of the experimental system per- formance becomes an essential part of the analytical workflow. A variety of the so-called quality control (QC) tools measuring this performance in advance of sophisticated and expensive analyses have been developed and used in practice in many proteomic laboratories worldwide. In the attempts of covering all aspects of LC–MS instrument operation, these tools are typically loaded with a high number of metrics that require performing large-scale analyses using complex standard digest mixtures followed by exten- sive data processing. Yet, a rapid and simple assessment of the instrument’s readiness for a large-scale proteome analysis is often everything needed in routine laboratory practice. In this work we propose a new MS/MS-based quality score which allows performing this assessment without employing full-scale experimental work with annotated samples and time-consuming data analysis. The proposed metric shows high specificity and accurate assessment of the analytical runs and can be used with single protein digest standards. It also allows clear graphical visualization of the quality of the run that makes it useful for day-to-day practice. © 2017 Published by Elsevier B.V. 1. Introduction Tandem mass-spectrometry (MS/MS) combined with liquid chromatography (LC) is widely used for proteome analysis. One of the main objectives of deep proteome characterization using high resolution, high throughput LC–MS/MS system is the identification of proteins in the whole cell or tissue lysates. This characteriza- tion is commonly performed by so-called “bottom-up” approach, which includes a lot of sample preparation and handling steps, such as lysis, purification, fractionation, enzymatic digestion of the proteins, and peptide separation followed by LC–MS/MS analysis [1–3]. In the course of this analysis the state-of-the-art LC–MS/MS instruments produce large volumes of data. The standard day-to- day laboratory practice includes optimization of the experimental parameters for improving the quality of these data. Because of the large number of parameters affecting the outcome of the analysis, the proper quality control (QC) over the performance of LC–MS/MS system is crucial for saving valuable instrument time and the sam- * Corresponding author at: V.L.Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia. E-mail address: gorshkov@chph.ras.ru (M.V. Gorshkov). ples which can be present in a limited amount, such as the ones obtained from patients. Significance of the QC step in the work- flow of LC–MS/MS analysis has been grasped by the community for years, and a variety of approaches or metrics to quantify the performance of the LC–MS/MS system or the quality of the spec- tra have been proposed. In a seminal work by CPTAC consortium (Clinical Proteomic Technology Assessment for Cancer) a set of 46 LC–MS/MS system performance metrics was described and evalu- ated [4]. The proposed set of metrics allows monitoring the status of all crucial elements and steps of the proteomic analysis workflow including the performance and stability of the chromatographic system, ionization source, mass spectra acquisition, fragmentation of ions, and data analysis. In the follow-up efforts, a number of QC tools and software implementing these metrics in practice were developed [5–11]. Later, it was shown that these metrics allow unambiguous distinguishing between “poor” and “good” results of the proteomic analyses in either supervised [12], or unsupervised [13] manner. Having a large number of QC metrics for monitoring LC–MS/MS system performance allows comprehending almost all aspects of system operation, data acquisition and analysis. On the other hand, this requires experienced and highly skillful involvement of the operator of a mass spectrometer to correctly and timely interpret http://dx.doi.org/10.1016/j.ijms.2017.09.008 1387-3806/© 2017 Published by Elsevier B.V.