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Viromics approaches for the study of viral diversity and ecology in microbiomes

Abstract

Viruses are found across all ecosystems and infect every type of organism on Earth. Traditional culture-based methods have proven insufficient to explore this viral diversity at scale, driving the development of viromics, the sequence-based analysis of uncultivated viruses. Viromics approaches have been particularly useful for studying viruses of microorganisms, which can act as crucial regulators of microbiomes across ecosystems. They have already revealed the broad geographic distribution of viral communities and are progressively uncovering the expansive genetic and functional diversity of the global virome. Moving forward, large-scale viral ecogenomics studies combined with new experimental and computational approaches to identify virus activity and host interactions will enable a more complete characterization of global viral diversity and its effects.

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Fig. 1: Overview of the viromics sample processing and computational pipelines.
Fig. 2: Global diversity and distribution of viruses currently captured from metagenomes.
Fig. 3: Identification and characterization of putative AMGs and other virus-encoded genes of interest based on metagenome-assembled genomes.
Fig. 4: Host prediction methods and their interpretation in viromics.
Fig. 5: Complementary approaches for in situ viral activity measurement.

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References

  1. Koonin, E. V., Kuhn, J. H., Dolja, V. V. & Krupovic, M. Megataxonomy and global ecology of the virosphere. ISME J. 18, wrad042 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Koonin, E. V. et al. Global organization and proposed megataxonomy of the virus world. Microbiol. Mol. Biol. Rev. 84, e00061–19 (2020). This review proposes a global genome-based viral classification framework that integrates both isolate and metagenome-assembled viral genomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Suttle, C. A. Marine viruses — major players in the global ecosystem. Nat. Rev. Microbiol. 5, 801–812 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Bratbak, G., Egge, J. K. & Heldal, M. Viral mortality of the marine alga Emiliania huxleyi (Haptophyceae) and termination of algal blooms. Mar. Ecol. Prog. Ser. 93, 39–48 (1993).

    Article  Google Scholar 

  5. Coy, S. R., Gann, E. R., Pound, H. L., Short, S. M. & Wilhelm, S. W. Viruses of eukaryotic algae: diversity, methods for detection, and future directions. Viruses 10, 487 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lennon, J. T. & Martiny, J. B. H. Rapid evolution buffers ecosystem impacts of viruses in a microbial food web. Ecol. Lett. 11, 1178–1188 (2008).

    Article  PubMed  Google Scholar 

  7. Albright, M. B. N. et al. Experimental evidence for the impact of soil viruses on carbon cycling during surface plant litter decomposition. ISME Commun. 2, 24 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Weitz, J. S. & Wilhelm, S. W. Ocean viruses and their effects on microbial communities and biogeochemical cycles. F1000 Biol. Rep. 4, 17 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Runa, V., Wenk, J., Bengtsson, S., Jones, B. V. & Lanham, A. B. Bacteriophages in biological wastewater treatment systems: occurrence, characterization, and function. Front. Microbiol. 12, 730071 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Carreira, C. et al. Integrating viruses into soil food web biogeochemistry. Nat. Microbiol. 9, 1918–1928 (2024).

    Article  CAS  PubMed  Google Scholar 

  11. Roux, S. A viral ecogenomics framework to uncover the secrets of nature’s ‘microbe whisperers’. mSystems 4, 1–5 (2019).

    Article  Google Scholar 

  12. Vela, J. D. & Al-Faliti, M. Emerging investigator series: the role of phage lifestyle in wastewater microbial community structures and functions: insights into diverse microbial environments. Environ. Sci. Water Res. Technol. 9, 1982–1991 (2023).

    Article  Google Scholar 

  13. Pires, D. P., Cleto, S., Sillankorva, S., Azeredo, J. & Lu, T. K. Genetically engineered phages: a review of advances over the last decade. Microbiol. Mol. Biol. Rev. 80, 523–543 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tringe, S. G. & Rubin, E. M. Metagenomics: DNA sequencing of environmental samples. Nat. Rev. Genet. 6, 805–814 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Edwards, R. A. & Rohwer, F. Viral metagenomics. Nat. Rev. Microbiol. 3, 504–510 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Breitbart, M. et al. Genomic analysis of uncultured marine viral communities. Proc. Natl Acad. Sci. USA 99, 14250–14255 (2002). This is one of the first viral metagenomic analyses from an environmental sample, highlighting the high number of novel genes encoded by viruses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Breitbart, M. et al. Metagenomic analyses of an uncultured viral community from human feces. J. Bacteriol. 185, 6220–6223 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Camargo, A. P. et al. IMG/VR v4: an expanded database of uncultivated virus genomes within a framework of extensive functional, taxonomic, and ecological metadata. Nucleic Acids Res. 51, D733–D743 (2023). IMG/VR is a large database integrating metagenome-assembled viral genomes from a broad range of ecosystems.

    Article  CAS  PubMed  Google Scholar 

  19. Camarillo-Guerrero, L. F., Almeida, A., Rangel-Pineros, G., Finn, R. D. & Lawley, T. D. Massive expansion of human gut bacteriophage diversity. Cell 184, 1098–1109.e9 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ma, B. et al. Biogeographic patterns and drivers of soil viromes. Nat. Ecol. Evol. 8, 717–728 (2024).

    Article  PubMed  Google Scholar 

  21. Shi, M. et al. Redefining the invertebrate RNA virosphere. Nature 540, 539–543 (2016).

    Article  CAS  PubMed  Google Scholar 

  22. Ng, T. F. F. et al. Preservation of viral genomes in 700-y-old caribou feces from a subarctic ice patch. Proc. Natl Acad. Sci. USA 111, 16842–16847 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tisza, M. J. et al. Discovery of several thousand highly diverse circular DNA viruses. eLife 9, e51971 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chiu, C. Y. & Miller, S. A. Clinical metagenomics. Nat. Rev. Genet. 20, 341–355 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dutilh, B. E. et al. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nat. Commun. 5, 4498 (2014). This article was the first to describe the CrAssphage genome, highlighting the potential of viromics for the discovery of novel highly abundant viruses.

    Article  CAS  PubMed  Google Scholar 

  26. Yutin, N. et al. Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut. Nat. Microbiol. 3, 38–46 (2018).

    Article  CAS  PubMed  Google Scholar 

  27. Edwards, R. A. et al. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage. Nat. Microbiol. 4, 1727–1736 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Roux, S. et al. Ecogenomics and potential biogeochemical impacts of uncultivated globally abundant ocean viruses. Nature 537, 689–693 (2016).

    Article  CAS  PubMed  Google Scholar 

  29. ter Horst, A. M. et al. Minnesota peat viromes reveal terrestrial and aquatic niche partitioning for local and global viral populations. Microbiome 9, 1–18 (2021).

    Google Scholar 

  30. Breitbart, M., Bonnain, C., Malki, K. & Sawaya, N. A. Phage puppet masters of the marine microbial realm. Nat. Microbiol. 3, 754–766 (2018). This Review presents an overview of the AMGs discovered at the time in marine phages and highlights the different cellular processes possibly impacted.

    Article  CAS  PubMed  Google Scholar 

  31. Sieradzki, E. T., Ignacio-Espinoza, J. C., Needham, D. M., Fichot, E. B. & Fuhrman, J. A. Dynamic marine viral infections and major contribution to photosynthetic processes shown by spatiotemporal picoplankton metatranscriptomes. Nat. Commun. 10, 1169 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Sharon, I. et al. Photosystem I gene cassettes are present in marine virus genomes. Nature 461, 258–262 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kieft, K. et al. Ecology of inorganic sulfur auxiliary metabolism in widespread bacteriophages. Nat. Commun. 12, 3503 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Emerson, J. B. et al. Host-linked soil viral ecology along a permafrost thaw gradient. Nat. Microbiol. 3, 870–880 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chen, L.-X. et al. Large freshwater phages with the potential to augment aerobic methane oxidation. Nat. Microbiol. 5, 1504–1515 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ahlgren, N. A., Fuchsman, C. A., Rocap, G. & Fuhrman, J. A. Discovery of several novel, widespread, and ecologically distinct marine Thaumarchaeota viruses that encode amoC nitrification genes. ISME J. 13, 618–631 (2019).

    Article  CAS  PubMed  Google Scholar 

  37. Braga, L. P. P. et al. Viruses direct carbon cycling in lake sediments under global change. Proc. Natl Acad. Sci. USA 119, e2202261119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schwartz, D. A. et al. Human-gut phages harbor sporulation genes. mBio 14, e00182–23 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Pausch, P. et al. CRISPR–CasΦ from huge phages is a hypercompact genome editor. Science 369, 333–337 (2020). This study highlights the unique features relevant for biotechnological applications of a phage-encoded Cas gene initially discovered via viromics.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Palmer, M. et al. Diversity and distribution of a novel genus of hyperthermophilic aquificae viruses encoding a proof-reading family — a DNA polymerase. Front. Microbiol. 11, 1–18 (2020).

    Article  Google Scholar 

  41. Garmaeva, S. et al. Transmission and dynamics of mother-infant gut viruses during pregnancy and early life. Nat. Commun. 15, 1945 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang, F. et al. Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease. Nat. Commun. 12, 65 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lam, S. et al. Roles of the gut virome and mycobiome in faecal microbiota transplantation. Lancet Gastroenterol. Hepatol. 7, 472–484 (2022).

    Article  CAS  PubMed  Google Scholar 

  44. Daly, R. A. et al. Viruses control dominant bacteria colonizing the terrestrial deep biosphere after hydraulic fracturing. Nat. Microbiol. 4, 352–361 (2019).

    Article  CAS  PubMed  Google Scholar 

  45. Medvedeva, S. et al. Three families of Asgard archaeal viruses identified in metagenome-assembled genomes. Nat. Microbiol. 7, 962–973 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Medvedeva, S., Borrel, G., Krupovic, M. & Gribaldo, S. A compendium of viruses from methanogenic archaea reveals their diversity and adaptations to the gut environment. Nat. Microbiol. 8, 2170–2182 (2023).

    Article  CAS  PubMed  Google Scholar 

  47. Rambo, I. M., Langwig, M. V., Leão, P., De Anda, V. & Baker, B. J. Genomes of six viruses that infect Asgard archaea from deep-sea sediments. Nat. Microbiol. 7, 953–961 (2022).

    Article  CAS  PubMed  Google Scholar 

  48. Hwang, Y., Roux, S., Coclet, C., Krause, S. J. E. & Girguis, P. R. Viruses interact with hosts that span distantly related microbial domains in dense hydrothermal mats. Nat. Microbiol. 8, 946–957 (2023). This study of deep-sea metagenomes reports a potentially broad range of interactions for some viruses and highlights several potential mechanisms for such interactions to be observed.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Marbouty, M., Thierry, A., Millot, G. A. & Koszul, R. MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut. eLife 10, 1–51 (2021).

    Article  Google Scholar 

  50. Arkhipova, K. et al. Temporal dynamics of uncultured viruses: a new dimension in viral diversity. ISME J. 12, 199–211 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Knowles, B. et al. Lytic to temperate switching of viral communities. Nature 531, 533–537 (2016).

    Article  Google Scholar 

  52. Ignacio-Espinoza, J. C., Ahlgren, N. A. & Fuhrman, J. A. Long-term stability and Red Queen-like strain dynamics in marine viruses. Nat. Microbiol. 5, 265–271 (2020).

    Article  CAS  PubMed  Google Scholar 

  53. Conceição-Neto, N., Yinda, K. C., Van Ranst, M. & Matthijnssens, J. in The Human Virome: Methods and Protocols (eds. Moya, A. & Pérez Brocal, V.) 85–95 (Springer, 2018).

  54. Kleiner, M., Hooper, L. V. & Duerkop, B. A. Evaluation of methods to purify virus-like particles for metagenomic sequencing of intestinal viromes. BMC Genomics 16, 7 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Soria-Villalba, A. et al. Comparison of experimental methodologies based on bulk-metagenome and virus-like particle enrichment: pros and cons for representativeness and reproducibility in the study of the fecal human virome. Microorganisms 12, 162 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hayes, S., Mahony, J., Nauta, A. & van Sinderen, D. Metagenomic approaches to assess bacteriophages in various environmental niches. Viruses 9, 127 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Trubl, G. et al. Optimization of viral resuspension methods for carbon-rich soils along a permafrost thaw gradient. PeerJ 4, e1999 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Forterre, P. The virocell concept and environmental microbiology. ISME J. 7, 233–236 (2013).

    Article  CAS  PubMed  Google Scholar 

  59. Santos-Medellin, C. et al. Viromes outperform total metagenomes in revealing the spatiotemporal patterns of agricultural soil viral communities. ISME J. 15, 1956–1970 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kosmopoulos, J. C., Klier, K. M., Langwig, M. V., Tran, P. Q. & Anantharaman, K. Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology. Microbiome 12, 195 (2024). This benchmarking study highlights the differences between and complementarity of different metagenomics approaches for viromics studies.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lücking, D., Mercier, C., Alarcón-Schumacher, T. & Erdmann, S. Extracellular vesicles are the main contributor to the non-viral protected extracellular sequence space. ISME Commun. 3, 112 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Shkoporov, A. N. et al. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe 26, 527–541.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  63. Labonté, J. M. et al. Single-cell genomics-based analysis of virus–host interactions in marine surface bacterioplankton. ISME J. 9, 2386–2399 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Jarett, J. K. et al. Insights into the dynamics between viruses and their hosts in a hot spring microbial mat. ISME J. 14, 2527–2541 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Martinez-Hernandez, F. et al. Single-virus genomics reveals hidden cosmopolitan and abundant viruses. Nat. Commun. 8, 15892 (2017). This application of single-virus genomics to oceanic samples uncovers a widespread virus population difficult to assemble from metagenomes, highlighting a potential blind spot for some viromics analyses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hillary, L. S., Adriaenssens, E. M., Jones, D. L. & McDonald, J. E. RNA-viromics reveals diverse communities of soil RNA viruses with the potential to affect grassland ecosystems across multiple trophic levels. ISME Commun. 2, 34 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Potapov, S. et al. RNA-seq virus fraction in Lake Baikal and treated wastewaters. Int. J. Mol. Sci. 24, 12049 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cook, R. et al. The long and short of it: benchmarking viromics using illumina, nanopore and PacBio sequencing technologies. Microb. Genomics 10, 001198 (2024).

    Article  CAS  Google Scholar 

  69. Warwick-Dugdale, J. et al. Long-read powered viral metagenomics in the oligotrophic Sargasso Sea. Nat. Commun. 15, 4089 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hopkins, M. et al. Diversity of environmental single-stranded DNA phages revealed by PCR amplification of the partial major capsid protein. ISME J. 8, 2093–2103 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Potapov, S. et al. Assessing the diversity of the g23 gene of T4-like bacteriophages from Lake Baikal with high-throughput sequencing. FEMS Microbiol. Lett. 365, fnx264 (2018).

    Article  Google Scholar 

  72. Frantzen, C. A. & Holo, H. Unprecedented diversity of lactococcal group 936 bacteriophages revealed by amplicon sequencing of the portal protein gene. Viruses 11, 443 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Munson-McGee, J. H., Rooney, C. & Young, M. J. An uncultivated virus infecting a nanoarchaeal parasite in the hot springs of Yellowstone national park. J. Virol. 94, e01213–e01219 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lund, M. C. et al. Diverse microviruses circulating in invertebrates within a lake ecosystem. J. Gen. Virol. 105, 002049 (2024).

    Article  CAS  Google Scholar 

  75. Lopez, J. K. M. et al. Genomes of bacteriophages belonging to the orders caudovirales and petitvirales identified in fecal samples from pacific flying Fox (Pteropus tonganus) from the kingdom of Tonga. Microbiol. Resour. Announc. 11, e00038–22 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Marine, R. et al. Caught in the middle with multiple displacement amplification: the myth of pooling for avoiding multiple displacement amplification bias in a metagenome. Microbiome 2, 3 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kim, K.-H. & Bae, J.-W. Amplification methods bias metagenomic libraries of uncultured single-stranded and double-stranded DNA viruses. Appl. Env. Microbiol. 77, 7663–7668 (2011).

    Article  CAS  Google Scholar 

  78. Roux, S. et al. Minimum information about an uncultivated virus genome (MIUVIG). Nat. Biotechnol. 37, 29–37 (2019). This consensus paper outlines key approaches for recovery and analysis of uncultivated virus genomes and the critical metadata to report when submitting these genomes to public databases.

    Article  CAS  PubMed  Google Scholar 

  79. Zolfo, M. et al. Detecting contamination in viromes using ViromeQC. Nat. Biotechnol. 37, 1408–1412 (2019).

    Article  CAS  PubMed  Google Scholar 

  80. Pinto, Y. & Bhatt, A. S. Sequencing-based analysis of microbiomes. Nat. Rev. Genet. 25, 829–845 (2024).

    Article  CAS  PubMed  Google Scholar 

  81. Meyer, F. et al. Critical assessment of metagenome interpretation: the second round of challenges. Nat. Methods 19, 429–440 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Nurk, S., Meleshko, D., Korobeynikov, A. & Pevzner, P. A. metaSPAdes: a new versatile metagenomic assembler. Genome Res. 27, 824–834 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Li, D. et al. MEGAHIT v1.0: a fast and scalable metagenome assembler driven by advanced methodologies and community practices. Methods 102, 3–11 (2016).

    Article  CAS  PubMed  Google Scholar 

  84. Antipov, D., Raiko, M., Lapidus, A. & Pevzner, P. A. Metaviral SPAdes: assembly of viruses from metagenomic data. Bioinformatics 36, 4126–4129 (2020).

    Article  CAS  PubMed  Google Scholar 

  85. Roux, S., Emerson, J. B., Eloe-Fadrosh, E. A. & Sullivan, M. B. Benchmarking viromics: an in silico evaluation of metagenome-enabled estimates of viral community composition and diversity. PeerJ 5, e3817 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Kieft, K., Adams, A., Salamzade, R., Kalan, L. & Anantharaman, K. vRhyme enables binning of viral genomes from metagenomes. Nucleic Acids Res. 50, e83 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Johansen, J. et al. Genome binning of viral entities from bulk metagenomics data. Nat. Commun. 13, 965 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schulz, F. et al. Advantages and limits of metagenomic assembly and binning of a giant virus. mSystems 5, e00048–20 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Camargo, A. P. et al. Identification of mobile genetic elements with geNomad. Nat. Biotechnol. 42, 1303–1312 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Kieft, K., Zhou, Z. & Anantharaman, K. VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences. Microbiome 8, 90 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Guo, J. et al. VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses. Microbiome 9, 37 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Ren, J. et al. Identifying viruses from metagenomic data using deep learning. Quant. Biol. 8, 64–77 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hegarty, B. et al. Benchmarking informatics approaches for virus discovery: caution is needed when combining in silico identification methods. mSystems 9, e01105–e01123 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Nayfach, S. et al. CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nat. Biotechnol. 39, 578–585 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Terzian, P. et al. PHROG: families of prokaryotic virus proteins clustered using remote homology. Nar. Genomics Bioinforma. 3, lqab067 (2021).

    Article  Google Scholar 

  96. Shaffer, M. et al. DRAM for distilling microbial metabolism to automate the curation of microbiome function. Nucleic Acids Res. 48, 8883–8900 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jang, H. B. et al. Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks. Nat. Biotechnol. 37, 632–639 (2019).

    Article  Google Scholar 

  98. Coclet, C. & Roux, S. Global overview and major challenges of host prediction methods for uncultivated phages. Curr. Opin. Virol. 49, 117–126 (2021).

    Article  CAS  PubMed  Google Scholar 

  99. Pratama, A. A. et al. Expanding standards in viromics: in silico evaluation of dsDNA viral genome identification, classification, and auxiliary metabolic gene curation. PeerJ 9, e11447 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Zhou, Z., Martin, C., Kosmopoulos, J. C. & Anantharaman, K. ViWrap: a modular pipeline to identify, bin, classify, and predict viral–host relationships for viruses from metagenomes. iMeta 2, e118 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Coclet, C., Camargo, A. P. & Roux, S. MVP: a modular viromics pipeline to identify, filter, cluster, annotate, and bin viruses from metagenomes. mSystems 9, e00888–24 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Páez-Espino, D. et al. Uncovering earth’s virome. Nature 536, 425–430 (2016).

    Article  PubMed  Google Scholar 

  103. Enault, F. et al. Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J. 11, 237–247 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Anantharaman, K. et al. Sulfur oxidation genes in diverse deep-sea viruses. Science 344, 757–760 (2014). This report and analysis of sulfur oxidation AMGs in metagenome-assembled virus genomes significantly expanded the list of metabolic processes potentially redirected during viral infections.

    Article  CAS  PubMed  Google Scholar 

  105. Nayfach, S. et al. Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nat. Microbiol. 6, 960–970 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gregory, A. C. et al. The gut virome database reveals age-dependent patterns of virome diversity in the human gut. Cell Host Microbe 28, 724–740.e8 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. An, L. et al. Global diversity and ecological functions of viruses inhabiting oil reservoirs. Nat. Commun. 15, 6789 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Brum, J. R. et al. Ocean plankton. Patterns and ecological drivers of ocean viral communities. Science 348, 1261498 (2015).

    Article  PubMed  Google Scholar 

  109. Gregory, A. C. et al. Marine DNA viral macro- and microdiversity from pole to pole. Cell 177, 1109–1123.e14 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Graham, E. B. et al. A global atlas of soil viruses reveals unexplored biodiversity and potential biogeochemical impacts. Nat. Microbiol. 9, 1873–1883 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Neri, U. et al. Expansion of the global RNA virome reveals diverse clades of bacteriophages. Cell 185, 4023–4037.e18 (2022).

    Article  CAS  PubMed  Google Scholar 

  112. Edgar, R. C. et al. Petabase-scale sequence alignment catalyses viral discovery. Nature 602, 142–147 (2022).

    Article  CAS  PubMed  Google Scholar 

  113. Zayed, A. A. et al. Cryptic and abundant marine viruses at the evolutionary origins of Earth’s RNA virome. Science 376, 156–162 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Wang, R. H. et al. PhageScope: a well-annotated bacteriophage database with automatic analyses and visualizations. Nucleic Acids Res. 52, D756–D761 (2024).

    Article  CAS  PubMed  Google Scholar 

  115. Willner, D., Thurber, R. V. & Rohwer, F. Metagenomic signatures of 86 microbial and viral metagenomes. Environ. Microbiol. 11, 1752–1766 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. Dinsdale, E. A. et al. Functional metagenomic profiling of nine biomes. Nature 452, 629–632 (2008).

    Article  CAS  PubMed  Google Scholar 

  117. Zhou, Z. et al. Unravelling viral ecology and evolution over 20 years in a freshwater lake. Nat. Microbiol. 10, 231–245 (2025).

    Article  CAS  PubMed  Google Scholar 

  118. Coclet, C. et al. Virus diversity and activity is driven by snowmelt and host dynamics in a high-altitude watershed soil ecosystem. Microbiome 11, 237 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bolaños, L. M., Michelsen, M. & Temperton, B. Metagenomic time series reveals a Western English Channel viral community dominated by members with strong seasonal signals. ISME J. 18, wrae216 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Sun, C. L. et al. Virus ecology and 7-year temporal dynamics across a permafrost thaw gradient. Environ. Microbiol. 26, e16665 (2024).

    Article  CAS  PubMed  Google Scholar 

  121. Muscatt, G., Cook, R., Millard, A., Bending, G. D. & Jameson, E. Viral metagenomics reveals diverse virus–host interactions throughout the soil depth profile. mBio 14, e02246–23 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Coutinho, F. H., Rosselli, R. & Rodríguez-Valera, F. Trends of microdiversity reveal depth-dependent evolutionary strategies of viruses in the Mediterranean. mSystems 4, e00554–19 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Pavlopoulos, G. A. et al. Unraveling the functional dark matter through global metagenomics. Nature 622, 594–602 (2023). This global reanalysis of public metagenomes reveals and describes a large number of novel protein families, many seemingly encoded by viruses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zayed, A. A. et al. efam: an expanded, metaproteome-supported HMM profile database of viral protein fam ilies. Bioinformatics 37, 4202–4208 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Fremin, B. J. et al. Thousands of small, novel genes predicted in global phage genomes. Cell Rep. 39, 110984 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Chevallereau, A., Pons, B. J., van Houte, S. & Westra, E. R. Interactions between bacterial and phage communities in natural environments. Nat. Rev. Microbiol. 20, 49–62 (2022).

    Article  CAS  PubMed  Google Scholar 

  127. van Kempen, M. et al. Fast and accurate protein structure search with Foldseek. Nat. Biotechnol. 42, 243–246 (2024).

    Article  PubMed  Google Scholar 

  128. Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Shao, B. & Yan, J. A long-context language model for deciphering and generating bacteriophage genomes. Nat. Commun. 15, 9392 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Hwang, Y., Cornman, A. L., Kellogg, E. H., Ovchinnikov, S. & Girguis, P. R. Genomic language model predicts protein co-regulation and function. Nat. Commun. 15, 2880 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Flamholz, Z. N., Biller, S. J. & Kelly, L. Large language models improve annotation of prokaryotic viral proteins. Nat. Microbiol. 9, 537–549 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Sullivan, M. B. et al. Prevalence and evolution of core photosystem II genes in marine cyanobacterial viruses and their hosts. PLoS Biol. 4, e234 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Lindell, D. et al. Transfer of photosynthesis genes to and from Prochlorococcus viruses. Proc. Natl Acad. Sci. USA 101, 11013–11018 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Mann, N. H., Cook, A., Millard, A., Bailey, S. & Clokie, M. Bacterial photosynthesis genes in a virus. Nature 424, 741–741 (2003). This first description of photosynthesis genes encoded by phages, reported here from isolate cyanophages, spurred the search for and subsequent discoveries of a large number of AMGs.

    Article  CAS  PubMed  Google Scholar 

  135. Puxty, R. J. & Millard, A. D. Functional ecology of bacteriophages in the environment. Curr. Opin. Microbiol. 71, 102245 (2023).

    Article  CAS  PubMed  Google Scholar 

  136. Brown, T. L., Charity, O. J. & Adriaenssens, E. M. Ecological and functional roles of bacteriophages in contrasting environments: marine, terrestrial and human gut. Curr. Opin. Microbiol. 70, 102229 (2022).

    Article  CAS  PubMed  Google Scholar 

  137. Johansen, J. et al. Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. Nat. Microbiol. 8, 1064–1078 (2023).

    Article  CAS  PubMed  Google Scholar 

  138. Kieft, K. et al. Virus-associated organosulfur metabolism in human and environmental systems. Cell Rep. 36, 109471 (2021).

    Article  CAS  PubMed  Google Scholar 

  139. Zheng, X. et al. Organochlorine contamination enriches virus-encoded metabolism and pesticide degradation associated auxiliary genes in soil microbiomes. ISME J. 16, 1397–1408 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Gao, R. et al. Ecological drivers and potential functions of viral communities in flooded arsenic-contaminated paddy soils. Sci. Total. Environ. 872, 162289 (2023).

    Article  CAS  PubMed  Google Scholar 

  141. Al-Shayeb, B. et al. Diverse virus-encoded CRISPR–Cas systems include streamlined genome editors. Cell 185, 4574–4586.e16 (2022).

    Article  CAS  PubMed  Google Scholar 

  142. Thompson, L. R. et al. Phage auxiliary metabolic genes and the redirection of cyanobacterial host carbon metabolism. Proc. Natl Acad. Sci. USA 108, E757–E764 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Hiraoka, S. et al. Diverse DNA modification in marine prokaryotic and viral communities. Nucleic Acids Res. 50, 1531–1550 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Seong, H. J., Roux, S., Hwang, C. Y. & Sul, W. J. Marine DNA methylation patterns are associated with microbial community composition and inform virus–host dynamics. Microbiome 10, 157 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Fu, Y. et al. DeepMineLys: deep mining of phage lysins from human microbiome. Cell Rep. 43, 114583 (2024).

    Article  CAS  PubMed  Google Scholar 

  146. Pottie, I., Vázquez Fernández, R., Van de Wiele, T. & Briers, Y. Phage lysins for intestinal microbiome modulation: current challenges and enabling techniques. Gut Microbes 16, 2387144 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Fischetti, V. Development of phage lysins as novel therapeutics: a historical perspective. Viruses 10, 310 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Coutinho, F. H. et al. RaFAH: host prediction for viruses of bacteria and archaea based on protein content. Patterns 2, 100274 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Amgarten, D., Iha, B. K. V., Piroupo, C. M., da Silva, A. M. & Setubal, J. C. vHULK, a new tool for bacteriophage host prediction based on annotated genomic features and neural networks. PHAGE 3, 204–212 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Edwards, R. A., McNair, K., Faust, K., Raes, J. & Dutilh, B. E. Computational approaches to predict bacteriophage–host relationships. FEMS Microbiol. Rev. 40, 258–272 (2016).

    Article  CAS  PubMed  Google Scholar 

  151. Roux, S. et al. iPHoP: An integrated machine learning framework to maximize host prediction for metagenome-derived viruses of archaea and bacteria. PLoS Biol. 21, e3002083 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Wang, W. et al. A network-based integrated framework for predicting virus–prokaryote interactions. Nar. Genomics Bioinforma. 2, lqaa044 (2020).

    Article  Google Scholar 

  153. Zhou, F. et al. PHISDetector: a tool to detect diverse in silico phage–host interaction signals for virome studies. Genomics, Proteom. Bioinforma. 20, 508–523 (2022).

    Article  Google Scholar 

  154. Boeckaerts, D. et al. Prediction of Klebsiella phage-host specificity at the strain level. Nat. Commun. 15, 4355 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Gaborieau, B. et al. Prediction of strain level phage–host interactions across the Escherichia genus using only genomic information. Nat. Microbiol. 9, 2847–2861 (2024).

    Article  CAS  PubMed  Google Scholar 

  156. Bastien, G. E. et al. Virus-host interactions predictor (VHIP): machine learning approach to resolve microbial virus–host interaction networks. PLOS Comput. Biol. 20, e1011649 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Kumar, M., Ji, B., Zengler, K. & Nielsen, J. Modelling approaches for studying the microbiome. Nat. Microbiol. 4, 1253–1267 (2019).

    Article  CAS  PubMed  Google Scholar 

  158. Sokol, N. W. et al. Life and death in the soil microbiome: how ecological processes influence biogeochemistry. Nat. Rev. Microbiol. 20, 415–430 (2022).

    Article  CAS  PubMed  Google Scholar 

  159. Meng, L. et al. Quantitative assessment of nucleocytoplasmic large DNA virus and host interactions predicted by co-occurrence analyses. mSphere 6, e01298–20 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Coenen, A. R. & Weitz, J. S. Limitations of correlation-based inference in complex virus–microbe communities. mSystems 3, e00084–18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Wu, R. et al. Hi-C metagenome sequencing reveals soil phage–host interactions. Nat. Commun. 14, 7666 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Uritskiy, G. et al. Accurate viral genome reconstruction and host assignment with proximity-ligation sequencing. Preprint at bioRxiv https://doi.org/10.1101/2021.06.14.448389 (2021).

  163. Marbouty, M., Baudry, L., Cournac, A. & Koszul, R. Scaffolding bacterial genomes and probing host–virus interactions in gut microbiome by proximity ligation (chromosome capture) assay. Sci. Adv. 3, e1602105 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Du, Y., Fuhrman, J. A. & Sun, F. ViralCC retrieves complete viral genomes and virus-host pairs from metagenomic Hi-C data. Nat. Commun. 14, 502 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Howard-Varona, C. et al. Regulation of infection efficiency in a globally abundant marine Bacteriodetes virus. ISME J. 00, 1–12 (2016).

    Google Scholar 

  166. Lindell, D. et al. Genome-wide expression dynamics of a marine virus and host reveal features of co-evolution. Nature 449, 83–86 (2007).

    Article  CAS  PubMed  Google Scholar 

  167. Owen, S. V. et al. A window into lysogeny: revealing temperate phage biology with transcriptomics. Microb. Genomics 6, e000330 (2020).

    Article  Google Scholar 

  168. Blasdel, B. G., Chevallereau, A., Monot, M., Lavigne, R. & Debarbieux, L. Comparative transcriptomics analyses reveal the conservation of an ancestral infectious strategy in two bacteriophage genera. ISME J. 11, 1988–1996 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Stough, J. M. A. et al. Molecular prediction of lytic vs lysogenic states for Microcystis phage: metatranscriptomic evidence of lysogeny during large bloom events. PLoS ONE 12, 1–17 (2017).

    Article  Google Scholar 

  170. Merges, D. et al. Metatranscriptomics reveals contrasting effects of elevation on the activity of bacteria and bacterial viruses in soil. Mol. Ecol. 32, 6552–6563 (2023).

    Article  CAS  PubMed  Google Scholar 

  171. Kuchina, A. et al. Microbial single-cell RNA sequencing by split-pool barcoding. Science 371, eaba5257 (2021). This study describes the development and application of a single-cell RNA sequencing method for prokaryotes, that provides a unique opportunity for detailed characterization of virus-host interactions.

    Article  CAS  PubMed  Google Scholar 

  172. Shen, Y. et al. High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host–phage activity associations in human gut microbiome. Protein Cell 16, 211–226 (2024).

    Article  PubMed Central  Google Scholar 

  173. Putzeys, L. et al. Exploring the transcriptional landscape of phage–host interactions using novel high-throughput approaches. Curr. Opin. Microbiol. 77, 102419 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Fromm, A. et al. Single-cell RNA-seq of the rare virosphere reveals the native hosts of giant viruses in the marine environment. Nat. Microbiol. 9, 1619–1629 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Hevroni, G., Vincent, F., Ku, C., Sheyn, U. & Vardi, A. Daily turnover of active giant virus infection during algal blooms revealed by single-cell transcriptomics. Sci. Adv. 9, eadf7971 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Santos-Medellín, C., Blazewicz, S. J., Pett-Ridge, J., Firestone, M. K. & Emerson, J. B. Viral but not bacterial community successional patterns reflect extreme turnover shortly after rewetting dry soils. Nat. Ecol. Evol. 7, 1809–1822 (2023). This time-series viromics analysis integrating bulk soil and viral fractions samples highlights distinct successional patterns between microbial and viral communities.

    Article  PubMed  Google Scholar 

  177. Van Goethem, M. W., Swenson, T. L., Trubl, G., Roux, S. & Northen, T. R. Characteristics of wetting-induced bacteriophage blooms in biological soil crust. mBio 10, 1–15 (2019).

    Google Scholar 

  178. Barnett, S. E. & Buckley, D. H. Metagenomic stable isotope probing reveals bacteriophage participation in soil carbon cycling. Environ. Microbiol. 25, 1785–1795 (2023).

    Article  CAS  PubMed  Google Scholar 

  179. Trubl, G. et al. Active virus–host interactions at sub-freezing temperatures in Arctic peat soil. Microbiome 9, 208 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Ngo, V. Q. H. et al. Establishing host–virus link through host metabolism: viral DNA SIP validation using T4 bacteriophage and E. coli. Curr. Microbiol. 81, 266 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Charon, J. et al. Consensus statement from the first RdRp summit: advancing RNA virus discovery at scale across communities. Front. Virol. 4, 1–10 (2024). This consensus statement reports on the discussions led at the first RdRP summit, which gathered experts from different fields around the topic of sequence-based RNA virus discovery.

    Article  Google Scholar 

  182. Simmonds, P. et al. Virus taxonomy in the age of metagenomics. Nat. Rev. Microbiol. 15, 161–168 (2017). This perspective represents a key step and statement by the ICTV towards the integration of metagenome-derived virus genomes in the formal virus taxonomy.

    Article  CAS  PubMed  Google Scholar 

  183. Lang, A. S., Buchan, A. & Burrus, V. Interactions and evolutionary relationships among bacterial mobile genetic elements. Nat. Rev. Microbiol. 23, 423–438 (2025).

    Article  CAS  PubMed  Google Scholar 

  184. Casjens, S. Prophages and bacterial genomics: what have we learned so far?: prophage genomics. Mol. Microbiol. 49, 277–300 (2003).

    Article  CAS  PubMed  Google Scholar 

  185. Holmes, E. C. The evolution of endogenous viral elements. Cell Host Microbe 10, 368–377 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Lang, A. S., Westbye, A. B. & Beatty, J. T. The distribution, evolution, and roles of gene transfer agents in prokaryotic genetic exchange. Annu. Rev. Virol. 4, 87–104 (2017).

    Article  CAS  PubMed  Google Scholar 

  187. Scholl, D. Phage tail–like bacteriocins. Annu. Rev. Virol. 4, 453–467 (2017).

    Article  CAS  PubMed  Google Scholar 

  188. Krupovic, M., Bamford, D. H. & Koonin, E. V. Conservation of major and minor jelly-roll capsid proteins in Polinton (Maverick) transposons suggests that they are bona fide viruses. Biol. Direct 9, 6 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Gaïa, M. et al. Mirusviruses link herpesviruses to giant viruses. Nature 616, 783–789 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  190. Zheludev, I. N. et al. Viroid-like colonists of human microbiomes. Cell 187, 6521–6536.e18 (2024).

    Article  CAS  PubMed  Google Scholar 

  191. Banfield, J. et al. Convergent evolution of viral-like Borg archaeal extrachromosomal elements and giant eukaryotic viruses. Preprint at bioRxiv https://doi.org/10.1101/2024.11.05.622173 (2024).

  192. Bolduc, B. et al. Identification of novel positive-strand RNA viruses by metagenomic analysis of archaea-dominated Yellowstone hot springs. J. Virol. 86, 5562–5573 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work conducted by the US Department of Energy Joint Genome Institute (https://ror.org/04xm1d337), a DOE Office of Science User Facility, is supported by the Office of Science of the US Department of Energy operated under contract no. DE-AC02-05CH11231.

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Roux, S., Coclet, C. Viromics approaches for the study of viral diversity and ecology in microbiomes. Nat Rev Genet (2025). https://doi.org/10.1038/s41576-025-00871-w

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