This document discusses the state of characterization of the eukaryotic proteome. It notes that as of 2019, around 20% of proteins in fission yeast and humans are still classified as having unknown biological processes. While the number of known or inferred protein roles has increased since 1992, progress in characterizing unknowns has been slow. Many recently characterized proteins in fission yeast are involved in non-core functions like environmental response, aging, and damage accumulation. The document calls for more research on these unknown and less studied proteins that are "hidden in plain sight" within the eukaryotic proteome.

1. What is left to discover in
the eukaryotic proteome?
GO users meeting, Berkeley, Oct 2019
Valerie Wood,
PomBase,
Department of Biochemistry,
University of Cambridge, UK

2. Only ~ 36% of predicted proteins were known
or inferred role
1992

3. “We’ll be done soon for sure…”
2002

4. https://www.pombase.org/status/gene-characterisation-statistics-history

5. Cofactor metabolic
process
DNA metabolic
process
cytoplasmic
translation
mitochondrial
translation
metabolic process

6. Intersection
Metabolic process ∩
cellular process 3167
‘High level’ terms are often uninformative for
physiological role
Fission yeast: 4369 proteins with biological process annotation
metabolic process
3237
75% of BP
annotated
proteins
cellular process
4112
Other process terms excluded
response to (chemical)
phosphorylation
(can also apply to any module)
Terms which apply across annotation space are
often too general to be informative about
physiological role (for a biologist).
Slims with specificity are more useful.

7. Classifying ‘knowns’ using 53 Gene Ontology
biological process
Terms selected align with recognised ‘modules’ of biology
2018

8. Matrix of co-annotation

9. Gene Ontology terms and intersections (biological modules)
5069 proteins
Unknown 700

10. Unknowns- the elephant in the room
Unknown 700
?

11. Slow progress characterizing unknowns
20% pombe and cerevisiae
still “unknown process”
Hidden in plain sight: what remains to be discovered in the eukaryotic proteome? PMID:30938578
2019

12. 117 terms
53 terms
Extended GO terms to
cover multicellular process
annotation
Hidden in plain sight: what remains to be discovered in the eukaryotic proteome? PMID:30938578
2019
20% of human also
unknown (confirmed this)
What about human?
70% of human research is on
proteins known pre genome
sequence (Edwards et al 2011 PMID:21307913)

13. Why are unknowns unstudied?
27
Based on recent gene characterizations
in fission yeast
Most recently characterised proteins are
involved in non-core functions:
● environment responsive or aging
related processes: detoxification,
proteostasis, lipidostasis, damage
accumulation.
● Processes that are only required over
longer timescales
● Less than 25% are “housekeeping “
processes
Hidden in plain sight: what remains to be discovered in the eukaryotic proteome? PMID:30938578
2019

14. Hidden in plain sight: what remains to be discovered in the eukaryotic proteome? PMID:30938578
2019

15. Acknowledgements
The PomBase team
Kim Rutherford, Uni. of Cambridge (developer)
Midori Harris, Uni. of Cambridge (curator, ontology
developer)
Antonia Lock, UCL(curator)
PIs
Steve Oliver, Uni. of Cambridge (Outgoing)
Juan Mata, Uni. of Cambridge (Incoming)
Jurg Bahler, Uni. UCL