A Compendium of 49 Experimental SBS Signatures for Decoding Human Cancer Mutational Processes
- 1UC San Diego
Abstract
Human cancer genomes harbor distinct mutational patterns that reflect past processes of DNA damage and repair. However, the precise attribution of these signatures to specific chemical carcinogens lacks a standardized experimental reference framework. To address this gap, we curated 4,282 genome-wide sequencing datasets from 42 model systems across five species exposed to 146 cancer-risk agents. This platform yielded 49 robust experimental single-base substitution signatures (eSS), with 28 matching 19 established COSMIC signatures and 21 defining novel mutational processes. We reconstructed 24 COSMIC signatures, assigning candidate etiologies to five signatures of unknown origin and revising two contested assignments. Pan-cancer decomposition detected four eSS-like mutational processes enriched in smokers across 4,951 tumors. Lastly, independent single-molecule sequencing of primary human organoids reproduced these profiles with high fidelity, confirming true platform-independent biological reproducibility across complex human models. This eSS repertoire provides a reference that links human mutational processes to mechanistic classes of DNA damage.
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BibTeX
@misc{zhivagui2026compendium,
title = {{A Compendium of 49 Experimental SBS Signatures for Decoding Human Cancer Mutational Processes}},
author = {M. Zhivagui and J. N. Au and S. Sharma and P. T. Nguyen and S. Al-Azzam and J. Zhang and M. Barnes and L. B. Alexandrov},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748400},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748400v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Compendium of 49 Experimental SBS Signatures for Decoding Human Cancer Mutational Processes
AU - M. Zhivagui
AU - J. N. Au
AU - S. Sharma
AU - P. T. Nguyen
AU - S. Al-Azzam
AU - J. Zhang
AU - M. Barnes
AU - L. B. Alexandrov
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748400
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748400v1
AB - Human cancer genomes harbor distinct mutational patterns that reflect past processes of DNA damage and repair. However, the precise attribution of these signatures to specific chemical carcinogens lacks a standardized experimental reference framework. To address this gap, we curated 4,282 genome-wide sequencing datasets from 42 model systems across five species exposed to 146 cancer-risk agents. This platform yielded 49 robust experimental single-base substitution signatures (eSS), with 28 matching 19 established COSMIC signatures and 21 defining novel mutational processes. We reconstructed 24 COSMIC signatures, assigning candidate etiologies to five signatures of unknown origin and revising two contested assignments. Pan-cancer decomposition detected four eSS-like mutational processes enriched in smokers across 4,951 tumors. Lastly, independent single-molecule sequencing of primary human organoids reproduced these profiles with high fidelity, confirming true platform-independent biological reproducibility across complex human models. This eSS repertoire provides a reference that links human mutational processes to mechanistic classes of DNA damage.
ER -