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. Author manuscript; available in PMC: 2020 Nov 1.
Published in final edited form as: Nat Med. 2020 Apr 13;26(5):769–780. doi: 10.1038/s41591-020-0815-6

Extended Data Figure 1. Analysis of Missing Protein Quantitative Measurements and their Effect on the AD Network.

Extended Data Figure 1.

(A-D) The percentage of quantified proteins with a given level of missing quantitative measurements was analyzed for both the consensus LFQ and ROS/MAP TMT networks (A). Each bar represents a bin of 2%. The red line indicates the 50% missing measurement threshold used in this study. The total number of quantified proteins for each dataset, and the percentage of quantified proteins removed due to ≥50% missing measurements prior to construction of the respective protein networks, is provided in the legend. (B) The effect of missing value threshold on AD network modules. The AD network was constructed using different allowed levels of missing protein measurements. Preservation of AD network modules (50% missingness threshold) in each network generated using a more stringent threshold (10–40% missingness) was assessed by Zsummary score. Module preservation Zsummary was calculated as described by Langfelder et al.73 The dashed blue line indicates a zsummary score of 1.96, or FDR q value <0.05, above which module preservation was considered statistically significant. The dashed red line indicates a zsummary score of 10, or FDR q value ~ 1e−23, above which module preservation was considered highly statistically significant. Each module is color coded as shown in Figure 1. Module memberships are provided in Supplementary Table 2. (C) Percentage of total quantified proteins with ≥50% missing measurements in each cohort used for the AD consensus network. The total number of quantified proteins, and the percentage removed by applying the ≥50% missingness threshold, is provided in the legend for each cohort. (D) Percentage of total quantified proteins with ≥50% missing measurements in each cohort used in this study. The total number of quantified proteins, and the percentage removed by applying the ≥50% missingness threshold, is provided in the legend for each cohort. For the consensus LFQ cohort, the dotted line indicates the percent removed (41.3%) when missingness is controlled separately in each cohort prior to combination for construction of the AD network, as was done in this study. The solid bar is provided for direct method comparison to other cohorts used in the study. LFQ, label-free quantitation; TMT, tandem-mass tag; BLSA, Baltimore Longitudinal Study of Aging, Banner, Banner Sun Health Research Institute; MSSB, Mount Sinai School of Medicine Brain Bank; ACT, Adult Changes in Thought Study; ROS/MAP, Religious Orders Study and Memory and Aging Project; PC, precuneus; TC, temporal cortex.