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Title: | Moderated Test Statistics to Detect Differential Deuteration in Hydrogen/Deuterium Exchange Mass Spectrometry Experiments | Authors: | CLAESEN, Jurgen Krishnamurthy, Srinath Lau, Andy M. Economou, Anastassios |
Issue Date: | 2021 | Publisher: | AMER CHEMICAL SOC | Source: | Analytical Chemistry, 93 (49) , p. 16341 -16349 | Abstract: | With differential hydrogen/deuterium exchange, differences in the structure and dynamics of protein states can be studied. Detecting statistically significant differentially deuterated peptides is crucial to draw meaningful conclusions about the distinct conformations and dynamics of the protein under study. Here, we introduced a linear model in combination with an empirical Bayes approach to detect differentially deuterated peptides. Using a linear model allows one to test for differences in deuteration between two (two-sample t-test) or more groups (F-statistic), while potentially controlling for the effects of other variables that are not of interest. The empirical Bayes approach improves the estimation of deuteration-level variances, especially in experiments with a low number of replicates. As a consequence, the two sample t-tests and the F-statistic become moderated, resulting in a lower number of false positive and false negative findings. Furthermore, we introduce a thresholded-moderated t-statistic to test if the observed deuteration differences are larger than a specified, biologically relevant difference. Finally, we underline the importance of having a sufficient number of replicates, and the effect of the number of replicates on the power of the statistical significance tests. The R-code for the proposed moderated test statistics is available upon request. | Notes: | Claesen, J (corresponding author), Vrije Univ Amsterdam, Dept Epidemiol & Data Sci, Amsterdam UMC, NL-1081 HV Amsterdam, Netherlands.; Claesen, J (corresponding author), Hasselt Univ, Data Sci Inst, I BioStat, B-3500 Hasselt, Belgium. j.claesen@amsterdamumc.nl |
Keywords: | Bayes Theorem;Deuterium;Proteins;Hydrogen;Hydrogen Deuterium Exchange-Mass Spectrometry | Document URI: | http://hdl.handle.net/1942/36962 | ISSN: | 0003-2700 | e-ISSN: | 1520-6882 | DOI: | 10.1021/acs.analchem.1c02346 | ISI #: | WOS:000753032200007 | Rights: | 2021 American Chemical Society | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
HDXMS_stats_AnalChem_final - revised_nov.pdf | Peer-reviewed author version | 4.04 MB | Adobe PDF | View/Open |
Moderated Test Statistics to Detect Differential Deuteration in Hydrogen_Deuterium Exchange Mass Spectrometry Experiments.pdf Restricted Access | Published version | 6.14 MB | Adobe PDF | View/Open Request a copy |
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