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The neXt50 challenge


1. Chromosome 1




2. Chromosome 2



Plans:
• Complete reannotation of the 33 missing proteins from chr 2 with associated literature - expected validation of ~20 proteins in September 2017
• Targeted studies (SRM, IHC) on the 40 probable sperm proteins listed in Duek et al. 2016 - expected validation of ~10 chromosome 2 proteins in April 2017 (collaboration with Chromosome 14 team)
• Data mining on the remaining chr2 MPs to define the best samples to track them - prioritized list expected May 2017


3. Chromosome 3




4. Chromosome 4




5. Chromosome 5


Plans:
  • Participation in IVTT cluster, which target the 50 missing proteins in chromosomes 5, 10, 15, 16, and 19 that has the highest probability for identification in COV318, PANC1, DFCI024, D341MED, ST486, KLE cell line determined using mRNA array expression.
  • Close collaboration with chromosome 19 team in Moonshot project performing deep profiling of 4000 melanoma samples and sharing bioinformatics expertise. In this project missing proteins can be obtained from deep profiling of large number of primary and metastatic melanoma samples.
  • European trasncan-2 project on ovarian cancer will allow to obtain primary and metastatic protein profiles on large number of ovarian cancer samples, where missing proteins is expected to be identified.
  • Local project on proteogenomics profiling of human lung tissue in context of COPD. Human lung tissue is highly complex in term of cell types, which can be the source of multiple missing proteins.

6. Chromosome 6




7. Chromosome 7




8. Chromosome 8




9. Chromosome 9




10. Chromosome 10




11. Chromosome 11




12. Chromosome 12




13. Chromosome 13



Top-Down Approaches
  • Steps
    1. 20~30 missing proteins from liver (normal-like, tumor, and/or cell lines) in all Chr. mapped
    2. 20~30 missing proteins from pancreas (normal-like, tumor, and/or cell lines ) in all Chr. mapped
    3. 10~20 missing proteins from placenta (normal, pre-eclampcia) in all Chr. mapped
    • Total missing proteins: 50 in all Chr. mapped
  • Milestone dates:
    • Step 1. Jul. 2017
    • Step 2. Feb. 2018
    • Step 3. Aug. 2018
Bottom-Up Approaches
  • Steps
    1. Select target missing proteins under criteria (available/target sample, transcript expression level, number of proteotypic peptides, etc..)
    2. makes synthetic peptides’ MS spectrum of target proteins.
    3. Discovering and validating missing proteins.
    • Total missing proteins: 50 in all Chr. mapped
  • Milestone dates:
    • Step 1. Feb. 2017
    • Step 2. Feb. 2018
    • Step 3. Aug. 2018


14. Chromosome 14




15. Chromosome 15




16. Chromosome 16


Step by step milestone plan to find, identify and validate MPs:

• Prioritization of the 50 chr16 MPs to be targeted. Annotation with Missing Proteinpedia, HPA, Human MRM Atlas and Chr16 already generated information. February 2017.
• List of chr16 MPs that would require non standard procedures (non-trypsin digestion sites, lack of unique peptides...). March 2017.
• Preparation of SRM methods and identification of the biological sources with highest probability of finding the selected chr16 MPs. June 2017
• SRM analysis, 10 MPS/lab. Starting on June-July 2017).
• IVTT initiative (5 chromosomes participating). 5-10 proteins/year. (2 MPs already identified by SRM and 2 aditional are pending on validation)




17. Chromosome 17




18. Chromosome 18




19. Chromosome 19




20. Chromosome 20




21. Chromosome 21




22. Chromosome 22




23. Chromosome X




24. Chromosome Y




25. Mitochondrial Chromosome