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A proposed short- and long-term plan to characterize human dark proteins of unknown functions. The terms, neXt-CP50 and neXt-CP2000 stand for characterizing 50 uPE1, a small set of dark proteins in 3 years (a pilot) and then ~2000 dark proteins (1260 uPE1 plus 677 uMPs) over a longer period of time. Term 'CP' stands for characterization of proteins with unknown functions. (from Paik et al., J. Proteome Res. 2018, 17, 4042−4050)

We believe that high-quality, extensive proteome maps are achievable within a planned 10-year period. During Phase 1 (6 years), the C-HPP group plans to map all proteins lacking good quality MS evidence, three major classes of PTMs, one representative alternative splicing transcription (AST) product [Menon, R. et al., Methods Mol Biol. 2011, 696, 319-26] and one non-synonymous SNP product, and protein distribution in a major organ/tissue of interest. C-HPP will utilize all high-quality consortium-generated proteomic datasets for focused analysis on individual chromosomes. In phase II (4 years), identified proteins will be further characterized and validated at the genomic/transcriptomic and cellular levels in the 4 selected tissues of interest. C-HPP outputs will also be integrated with all biology/disease-driven HPP research. We will also provide a correlation of C-HPP and B/D HPP study results with recent SNP and haplotypic mapping studies. [Im, KM. et al., Hum Genet. 2011, 130, 685-99.]

Table. The proposed two phases of C-HPP and short-term/long-term challenges [Paik. YK., et al., J Proteome Res. 2012, Just Accepted]
PhasePhase IPhase II
  • Organization, SOP and Guidelines
  • Mapping and characterization of 6000 missing proteins having no MS evidencea
  • Mapping the predicted three major PTMs (phosphoryl-, glycosyl-, acetyl-) of 10,000 well-known proteinsb
  • One representative AST and nsSNP of predicted c.a. 14,300 well-known proteins
  • Genomic/transcriptomic/proteomic validation of predicted c.a. 14,300 well-known proteins
  • Cellular localization and quantitation of newly identified proteins in at least three tissues
  • Further characterization of whole human proteins (~20,300) with respect to gene location on each chromosome, cellular distribution and quantitation
  • Validation of three major PTMs present in 20,300 human proteins
  • Validation of one representative AST and nsSNP of 20,300 well-known proteins
  • Genomic/transcriptomic validation of whole proteins in at least three representative tissues
  • Development of drug targets and biomarker candidates of interest.
  • Functional studies of gene families/clusters in each chromosome
Coping with short-term and longer-term challengesShort-TermSolutions
  • Sustainable funding/cost savings
  • Effective cross analysis and integration of different datasets
  • Handling of data variability
  • Harmonization with biology-driven projects
  • Procurement of affinity captured reagents
  • Sharing resources, data, and reagents (AB), ref specimens
  • Employing neXtProt, dbSNP, GPMDB and PeptideAtlas
  • Standard data submission system/criteria
  • Sharing data through C-HPP portal and other public DBs
  • Close collaborations between providers and C-HPP groups
  • Enhanced detection limit for low abundance (rare) proteins
  • Improved pretreatment of clinical specimens for characterization and SRM analysis
  • Inclusion of PTM information in different datasets
  • Sample bio-banking and maintenance
  • Miniaturization of sample preparation/efficient fractionations
  • Continued refinement of non-redundant protein list

  • Development of new algorithms for inclusion of PTMs
  • Collaboration with government agencies
aLess well-known: proteins that have only transcriptomic evidence, but not proteomic MS data (constitutes about 6,000 proteins).
bWell-known: proteins that have both transcriptomic and proteomics MS data. The data for proteins under investigation will be integrated into one common C-HPP portal by contributions from each chromosome team.