Better than flipping a coin? Organ specific plasma proteins are not confidently identified by gene expression data

Abstract

A recent study by Oh et al., utilized plasma proteomic samples to produce an impressive model predictive of human aging at an organ specific level. While both the depth and size of this study are nearly unprecedented, proteins were grouped by the organ they originated from based on gene expression data. This is surprising because it is well accepted that the correlation between protein abundance and transcript abundance is generally poor. It is more surprising that the authors did not leverage protein specific databases such as the Draft Maps of the Human Proteome published in Nature in 2014. Spot checking proteins these “organ specific” proteins against these resources suggested there was generally low levels of specificity. For a thorough analysis I compared all proteins identified as organ specific from a high depth proteomic atlas of 29 healthy human tissues. Of 460 proteins which could be matched to organ specific data between the two studies only 274 (59.6%) met the author’s threshold for organ specificity when evaluating protein level data. When considering human organs as a connected network with equivalent protein level contributions to plasma, only 209 (45.4%) of the organ specific proteins had a greater summed abundance than the other organs. While there may be validity in the use of plasma proteomics to assess human aging, organ specific patterns should be based on protein level data, rather than gene expression for reliable metric

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