Towards a reference human platelet transcriptome: evaluation of inter-individual correlations and of its relationship with a platelet proteome

For the anucleate platelet it has been unclear how well platelet transcriptomes correlate among different donors or across different RNA profiling platforms, and what the transcriptomes relationship is with the platelet proteome. We generated RNA-seq pro-files of the long RNA transcriptomes from the platelets of 10 healthy young males (5 white and 5 black) with median age of 24.5 years, no notable clinical history, and no pre-vious history of thrombosis or bleeding. We also profiled the subjects messenger RNAs using the Affymetrix microarray gene expression system. We found that the abundance of platelet mRNA transcripts was highly correlated across the 10 individuals, inde-pendently of race and of the employed technology. Our RNA-seq data also showed that these high inter-individual correlations extend beyond mRNAs to several categories of non-coding RNAs. Pseudogenes represented a notable exception to this by exhibiting a clear difference in expression by race. Comparison of our mRNA signatures with the only publicly available quantitative platelet proteome data showed that most (87.5%) identified platelet proteins had a detectable corresponding mRNA. However, a high number of mRNAs that were present in the transcriptomes of all 10 individuals had no representa-tion in the proteome. The Spearman correlation of the relative abundances for those platelet genes that were represented by both an mRNA and a protein showed a weak (~0.3) yet statistically significant (P=5.0E-16) connection. Further analysis of the overlap-ping and non-overlapping platelet mRNAs and proteins identified gene groups corre-sponding to distinct cellular processes, a finding that provides novel insights for platelet biology.

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Londin ER, Hatzimichael E, Loher P, Edelstein L, Shaw C, Delgrosso K, Fortina P, Bray PF, McKenzie SE, Rigoutsos I