NAguideR: performing and prioritizing missing value imputations for consistent bottom-up proteomic analyses

Nucleic Acids Res. 2020 Aug 20;48(14):e83. doi: 10.1093/nar/gkaa498.

Abstract

Mass spectrometry (MS)-based quantitative proteomics experiments frequently generate data with missing values, which may profoundly affect downstream analyses. A wide variety of imputation methods have been established to deal with the missing-value issue. To date, however, there is a scarcity of efficient, systematic, and easy-to-handle tools that are tailored for proteomics community. Herein, we developed a user-friendly and powerful stand-alone software, NAguideR, to enable implementation and evaluation of different missing value methods offered by 23 widely used missing-value imputation algorithms. NAguideR further evaluates data imputation results through classic computational criteria and, unprecedentedly, proteomic empirical criteria, such as quantitative consistency between different charge-states of the same peptide, different peptides belonging to the same proteins, and individual proteins participating protein complexes and functional interactions. We applied NAguideR into three label-free proteomic datasets featuring peptide-level, protein-level, and phosphoproteomic variables respectively, all generated by data independent acquisition mass spectrometry (DIA-MS) with substantial biological replicates. The results indicate that NAguideR is able to discriminate the optimal imputation methods that are facilitating DIA-MS experiments over those sub-optimal and low-performance algorithms. NAguideR further provides downloadable tables and figures supporting flexible data analysis and interpretation. NAguideR is freely available at http://www.omicsolution.org/wukong/NAguideR/ and the source code: https://github.com/wangshisheng/NAguideR/.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells / drug effects
  • Computer Simulation
  • Datasets as Topic
  • Formaldehyde / pharmacology
  • Humans
  • Mass Spectrometry
  • Microtubules / drug effects
  • Nocodazole / pharmacology
  • Protein Precursors / chemistry
  • Proteomics / methods*
  • Software*

Substances

  • Protein Precursors
  • Formaldehyde
  • Nocodazole