Magana, M. et al. The value of antimicrobial peptides in the age of resistance. Lancet Infect. Dis. 20, e216–e230 (2020).

Article  CAS  PubMed  Google Scholar 

Murray, C. J. L. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022).

Article  CAS  Google Scholar 

de la Fuente-Nunez, C., Torres, M. D., Mojica, F. J. & Lu, T. K. Next-generation precision antimicrobials: towards personalized treatment of infectious diseases. Curr. Opin. Microbiol. 37, 95–102 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Porto, W. F. et al. In silico optimization of a guava antimicrobial peptide enables combinatorial exploration for peptide design. Nat. Commun. 9, 1490 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Wong, F., de la Fuente-Nunez, C. & Collins, J. J. Leveraging artificial intelligence in the fight against infectious diseases. Science 381, 164–170 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maasch, J. R. M. A., Torres, M. D. T., Melo, M. C. R. & de la Fuente-Nunez, C. Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning. Cell Host Microbe 31, 1260–1274 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Torres, M. D. T. et al. Mining for encrypted peptide antibiotics in the human proteome. Nat. Biomed. Eng. 6, 67–75 (2022).

Article  PubMed  Google Scholar 

Wan, F., Torres, M. D. T., Peng, J. & de la Fuente-Nunez, C. Deep-learning-enabled antibiotic discovery through molecular de-extinction. Nat. Biomed. Eng. 8, 854–871 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diéguez-Santana, K. & González-Díaz, H. Towards machine learning discovery of dual antibacterial drug–nanoparticle systems. Nanoscale 13, 17854–17870 (2021).

Article  PubMed  Google Scholar 

Nocedo-Mena, D. et al. Modeling antibacterial activity with machine learning and fusion of chemical structure information with microorganism metabolic networks. J. Chem. Inf. Model. 59, 1109–1120 (2019).

Article  CAS  PubMed  Google Scholar 

Liu, G. et al. Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii. Nat. Chem. Biol. 19, 1342–1350 (2023).

Article  CAS  PubMed  Google Scholar 

Wong, F. et al. Discovery of a structural class of antibiotics with explainable deep learning. Nature 626, 177–185 (2024).

Article  CAS  PubMed  Google Scholar 

Hughes, J., Rees, S., Kalindjian, S. & Philpott, K. Principles of early drug discovery. Br. J. Pharmacol. 162, 1239–1249 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma, Y. et al. Identification of antimicrobial peptides from the human gut microbiome using deep learning. Nat. Biotechnol. 40, 921–931 (2022).

Article  CAS  PubMed  Google Scholar 

Torres, M. D. T. et al. Mining human microbiomes reveals an untapped source of peptide antibiotics. Cell 187, 5453–5467 (2024).

Article  CAS  PubMed  Google Scholar 

Santos-Júnior, C. D. et al. Discovery of antimicrobial peptides in the global microbiome with machine learning. Cell 187, 3761–3778.e16 (2024).

Article  PubMed  Google Scholar 

Pane, K. et al. Identification of novel cryptic multifunctional antimicrobial peptides from the human stomach enabled by a computational–experimental platform. ACS Synth. Biol. 7, 2105–2115 (2018).

Article  CAS  PubMed  Google Scholar 

Cesaro, A. et al. Synthetic antibiotic derived from sequences encrypted in a protein from human plasma. ACS Nano 16, 1880–1895 (2022).

Article  CAS  PubMed  Google Scholar 

Sberro, H. et al. Large-scale analyses of human microbiomes reveal thousands of small, novel genes. Cell 178, 1245–1259.e14 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, H. et al. FSPP: a tool for genome-wide prediction of smORF-encoded peptides and their functions. Front. Genet. 9, 96 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Torres, M. D. T., Sothiselvam, S., Lu, T. K. & de la Fuente-Nunez, C. Peptide design principles for antimicrobial applications. J. Mol. Biol. 431, 3547–3567 (2019).

Article  CAS  PubMed  Google Scholar 

Torres, M. D. T., Cesaro, A. & de la Fuente-Nunez, C. Peptides from non-immune proteins target infections through antimicrobial and immunomodulatory properties. Trends Biotechnol. 43, 184–205 (2025).

Article  CAS  PubMed  Google Scholar 

Yuanyuan, J. & Xinqiang, Y. Micropeptides identified from human genomes. J. Proteome Res. 21, 865–873 (2022).

Article  PubMed  Google Scholar 

Martinez, T. F. et al. Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins. Cell Metab. 35, 166–183.e11 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ruiz-Orera, J. & Albà, M. M. Translation of small open reading frames: roles in regulation and evolutionary innovation. Trends Genet. 35, 186–198 (2019).

Article  CAS  PubMed  Google Scholar 

Sandmann, C.-L. et al. Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames. Mol. Cell 83, 994–1011.e18 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Makarewich, C. A. & Olson, E. N. Mining for micropeptides. Trends Cell Biol. 27, 685–696 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vitorino, R., Guedes, S., Amado, F., Santos, M. & Akimitsu, N. The role of micropeptides in biology. Cell. Mol. Life Sci. 78, 3285–3298 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sousa, M. E. & Farkas, M. H. Micropeptide. PLoS Genet. 14, e1007764 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Eraslan, G., Avsec, Ž., Gagneur, J. & Theis, F. J. Deep learning: new computational modelling techniques for genomics. Nat. Rev. Genet. 20, 389–403 (2019).

Article  CAS  PubMed  Google Scholar 

Torres, M. D. T., Cao, J., Franco, O. L., Lu, T. K. & de la Fuente-Nunez, C. Synthetic biology and computer-based frameworks for antimicrobial peptide discovery. ACS Nano 15, 2143–2164 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar