Advances in the Chromosome-Centric Human Proteome Project: looking to the future

ABSTRACT

Introduction: The mission of the Chromosome-Centric Human Proteome Project (C-HPP), is to map and annotate the entire predicted human protein set (~20,000 proteins) encoded by each chromosome. The initial steps of the project are focused on ‘missing proteins (MPs)’, which lacked documented evidence for existence at protein level. In addition to remaining 2,579 MPs, we also target those annotated proteins having unknown functions, uPE1 proteins, alternative splice isoforms and post-translational modifications. We also consider how to investigate various protein functions involved in cis-regulatory phenomena, amplicons lncRNAs and smORFs.

Areas covered: We will cover the scope, historic background, progress, challenges and future prospects of C-HPP. This review also addresses the question of how we can best improve the methodological approaches, select the optimal biological samples, and recommend stringent protocols for the identification and characterization of MPs. A new strategy for functional analysis of some of those annotated proteins having unknown function will also be discussed.

Expert commentary: If the project moves well by reshaping the original goals, the current working modules and team work in the proposed extended planning period, it is anticipated that a progressively more detailed draft of an accurate chromosome-based proteome map will become available with functional information.

KEYWORDS:

• Chromosome-Centric Human Proteome Project
• functional annotation
• HUPO
• human protein atlas
• long non-coding RNA
• mass spectrometry
• missing proteins
• neXtProt
• peptideatlas
• protein evidence
• proteomexchange
• targeted proteomics
• smORF
• SRMAtlas

Acknowledgments

We thank proteomics scientists, leaders of public DBs, PIC members, and funding agencies. Special thanks go to Dr. Jin-Young Cho for his help on drawing the figures and JW Kim for their help preparing this manuscript. This paper is dedicated to all the C-HPP members as well as all other related investigators who contributed their efforts and data to move this global project forward in various ways.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by grants from the Korean Ministry of Health and Welfare: [HI13C2098]-International Consortium Project and [HI16C0257] (awarded to Y.-K. Paik), from the U.S. National Institutes of Health: [P30ES017885-01A1 and U24CA210967] (awarded to G.S.Omenn), and from Canadian Institutes of Health Research, 7-year Foundation Grant and Canada Research Chair in Protease Proteomics and Systems Biology: [FDN-148408] (awarded to C.M. Overal).