Identification of non-canonical peptides with moPepGen

Chenghao Zhu^#^{1

2

3

4}, Lydia Y Liu^#^{5

6

7

8

9}, Annie Ha^{7

8}, Takafumi N Yamaguchi^{5

6

10}, Helen Zhu^{7

8

9}, Rupert Hugh-White^{5

6

10}, Julie Livingstone^{5

6

10}, Yash Patel^{5

6

10}, Thomas Kislinger^{11

12}, Paul C Boutros^{13

14

15

16

17}

Affiliations

¹ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
² Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
³ Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
⁴ Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
⁵ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁸ Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
⁹ Vector Institute for Artificial Intelligence, Toronto, Ontario, Canada.
¹⁰ Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. thomas.kislinger@utoronto.ca.
¹² Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. thomas.kislinger@utoronto.ca.
¹³ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁴ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁵ Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁶ Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁷ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. pboutros@mednet.ucla.edu.

^# Contributed equally.

PMID: 40523945
DOI: 10.1038/s41587-025-02701-0

Identification of non-canonical peptides with moPepGen

Chenghao Zhu et al. Nat Biotechnol. 2025.

. 2025 Jun 16.

doi: 10.1038/s41587-025-02701-0. Online ahead of print.

Authors

Affiliations

¹ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
² Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
³ Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
⁴ Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. chenghaozhu@mednet.ucla.edu.
⁵ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁸ Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
⁹ Vector Institute for Artificial Intelligence, Toronto, Ontario, Canada.
¹⁰ Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. thomas.kislinger@utoronto.ca.
¹² Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. thomas.kislinger@utoronto.ca.
¹³ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁴ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁵ Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁶ Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. pboutros@mednet.ucla.edu.
¹⁷ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. pboutros@mednet.ucla.edu.

^# Contributed equally.

PMID: 40523945
DOI: 10.1038/s41587-025-02701-0

Abstract

Proteogenomics is limited by the challenge of modeling the complexities of gene expression. We create moPepGen, a graph-based algorithm that comprehensively generates non-canonical peptides in linear time. moPepGen works with multiple technologies, in multiple species and on all types of genetic and transcriptomic data. In human cancer proteomes, it enumerates previously unobservable noncanonical peptides arising from germline and somatic genomic variants, noncoding open reading frames, RNA fusions and RNA circularization.

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Conflict of interest statement

Competing interests: P.C.B. sits on the scientific advisory boards of Intersect Diagnostics and previously sat on those of Sage Bionetworks and BioSymetrics. The other authors declare no competing interests.

Update of

Identification of non-canonical peptides with moPepGen.
Zhu C, Liu LY, Ha A, Yamaguchi TN, Zhu H, Hugh-White R, Livingstone J, Patel Y, Kislinger T, Boutros PC. Zhu C, et al. bioRxiv [Preprint]. 2025 May 9:2024.03.28.587261. doi: 10.1101/2024.03.28.587261. bioRxiv. 2025. Update in: Nat Biotechnol. 2025 Jun 16. doi: 10.1038/s41587-025-02701-0. PMID: 38585946 Free PMC article. Updated. Preprint.

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Identification of non-canonical peptides with moPepGen

Affiliations

Identification of non-canonical peptides with moPepGen

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

References

Grants and funding

LinkOut - more resources

Full Text Sources