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  • Keynote lecture
  • KN-41

Microproteins and the non-canonical proteome in childhood cancer

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Conference room 5-6

Session

Functional diversity of proteoforms

Thema

  • Keynote Lecture

Mitwirkende

Sebastiaan van Heesch (Utrecht / NL)

Abstract

Ribosome profiling (Ribo-Seq) has proven transformative for our understanding of the human genome and proteome by illuminating thousands of noncanonical sites of ribosome translation outside the currently annotated coding sequences (CDSs). A conservative estimate suggests that at least 7000 noncanonical ORFs are translated, which, at first glance, has the potential to expand the number of human protein CDSs by 30%, from ~19,500 annotated CDSs to over 26,000 annotated CDSs. Yet, additional scrutiny of these ORFs has raised numerous questions about what fraction of them truly produce a protein product and what fraction of those can be understood as proteins according to the conventional understanding of the term. I will discuss the current state of noncanonical ORF research, databases, and interpretation, focusing on how to assess whether a given ORF can be said to be "protein coding." I will do so in the context of childhood cancer, where strategies targeting the small microproteins produced from these ORFs hold great promise for the development of new (immuno)therapies against these deadly early-onset cancers.

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