Abstract Number: PB1722
Meeting: ISTH 2020 Congress
Background: Recent advances in genome-wide platelet transcriptomics allow a first documentation of the complete proteome.
Aims: Compare platelet transcriptome and proteome.
Methods: Bottom-up identified human platelet proteomes of five cohorts (5,457 unique proteins). Genome-wide quantified transcripts (57,849 RNAs) in platelets and megakaryocytes from BLUEPRINT data; cut-off values for relevant expression. Supervised assignment to 21 platelet function classes (PFC) for 18,529 protein plus RNA genes.
Proteome. Integrative analysis of human platelet proteomes (5 cohorts) gave a total of 5,457 unique proteins (74% present in ≥2 databases), 3,692 of which with estimated copy numbers. Guided by UniProt-KB, the proteins were assigned over 21 PFC. Of these, 0.6% were not present in the transcriptome, whereas 6.7% did not have relevant expression (in majority secretory/extracellular proteins).
Transcriptome. The total relevant transcriptome of platelets and megakaryocytes was assessed at 15,356 and 17,205 RNA species, respectively. Of these, 12,239 RNA species were present in either cell type. Transcript levels in platelets and megakaryocytes were strongly correlated (r=0.8374, p< 0.0001). Relevant protein-coding transcripts were 12,863 (platelets) and 12,016 (megakaryocytes); the remainder being non-coding RNAs and pseudogenes. Levels of protein-encoding transcripts again were correlated (r=0.6852, p< 0.0001). Distribution profiles over PFC of these transcripts were highly similar (p< 0.01).
Comparison. Transcript levels maximised but did not otherwise determine protein abundance. Profiles of PFC were compared of the identified and the remaining expected platelets proteomes. This revealed over-representation of the following classes: actin cytoskeletal, membrane receptors/channels, metabolic and signalling proteins. However, under-representation of: mitochondrial, microtubular system, nuclear, proteasome and transcription protein classes. Equally present were: endoplasmic reticulum and other vesicular proteins.
(i) The full platelet proteome is expected at 12-13k, containing only part of the nuclear, proteasomal and microtubular proteins from megakaryocytes.
(ii) Protein-encoding transcriptomes of platelets and megakaryocytes are quantitatively similar, indicating free distribution of RNA species during proplatelet shedding.
To cite this abstract in AMA style:Huang J, Provenzale I, Grassi L, Solari FM, Sickmann A, Frontini M, Heemskerk JWM, Swieiringa F. Towards Complete Assignment of the Full Platelet Proteome and Transcriptome [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/towards-complete-assignment-of-the-full-platelet-proteome-and-transcriptome/. Accessed December 6, 2023.
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