PreprintCited by 50Genomics and Phylogenetic StudiesMachine Learning in Bioinformaticsvaccines and immunoinformatics approaches

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Whole-genome prediction of bacterial pathogenic capacity on novel bacteria using protein language models, with PathogenFinder2

Open access
Ferrer Florensa, Alfred, Almagro Armenteros, Jose Juan, Kaas, Rolf Sommer, Conradsen Clausen, Philip Thomas Lanken, Nielsen, Henrik, Rost, Burkhard, Aarestrup, Frank Møller·2025·Bioinformatics

Preprint — published as 10.1093/bioinformatics/btag129 · Paper page

Abstract

Infectious diseases continue to be a leading cause of mortality and pose a significant global health threat. Thus the development of tools for surveillance and early detection of emerging pathogens is needed. In this study, we introduce PathogenFinder2, a novel predictor of bacterial pathogenic capacity in humans, available through an online server ( http://genepi.food.dtu.dk/pathogenfinder2 ), or as a standalone program ( https://github.com/genomicepidemiology/PathogenFinder2 ). The model, using protein language models for whole-genome phenotype prediction, surpasses the performance of previous methods, especially for novel bacterial taxa, while being taxonomy-agnostic and alignment-free. At the same time, it predicts the importance of each protein for the pathogenic capacity. This output might aid in characterizing potential pathogens, it readily identifies new candidates for virulence factors and vaccine targets, and offers insights into infection metabolic pathways. Furthermore, we introduce the Bacterial Pathogenic Landscape, revealing distributions related to the host conditions, antagonist bacteria, infection site, or habitat.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2025.04.12.648497

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 47

  1. Florent Ailloud , Iratxe Estibariz , and Sebastian Suerbaum . Evolved to vary: genome and epigenome variation in the human pathogen helicobacter pylori. 45(1):fuaa042. · DOI
  2. D. Armstrong . History of opportunistic infection in the immunocompromised host. 17 Suppl 2:S318–321. · DOI
  3. M. S. Arons , L. Fernando , and I. M. Polayes . Pasteurella multocida–the major cause of hand infections following domestic animal bites. 7(1):47–52. · DOI
  4. Eran Barash , Neta Sal-Man , Sivan Sabato , and Michal Ziv-Ukelson . BacPaCS—bacterial pathogenicity classification via sparse-SVM. 35(12):2001–2008. · DOI
  5. Jakub M Bartoszewicz , Anja Seidel , Robert Rentzsch , and Bernhard Y Renard . DeePaC: predicting pathogenic potential of novel DNA with reverse-complement neural networks. 36(1):81–89. · DOI
  6. James Bergstra , Rémi Bardenet , Yoshua Bengio , and Balázs Kégl . Algorithms for hyper-parameter optimization. In Advances in Neural Information Processing Systems, volume 24. Curran Associates, Inc.
  7. Arturo Casadevall and Liise-anne Pirofski . The damage-response framework of microbial pathogenesis. 1(1):17–24. Publisher: Nature Publishing Group. · DOI
  8. Arturo Casadevall and Liise-anne Pirofski . Host-pathogen interactions: Basic concepts of microbial commensalism, colonization, infection, and disease. 68(12):6511–6518. · DOI
  9. Arturo Casadevall and Liise-Anne Pirofski . Virulence factors and their mechanisms of action: the view from a damage-response framework. 7 Suppl 1:S2–S18. · DOI
  10. 10.1080/078538902317338580 · DOI
  11. Philip T. L. C. Clausen , Frank M. Aarestrup , and Ole Lund . Rapid and precise alignment of raw reads against redundant databases with KMA. 19(19):307. · DOI
  12. Salvatore Cosentino , Mette Voldby Larsen , Frank Møller Aarestrup , and Ole Lund . PathogenFinder - distinguishing friend from foe using bacterial whole genome sequence data. 8(8):e77302. Publisher: Public Library of Science. · DOI
  13. Carlus Deneke , Robert Rentzsch , and Bernhard Y. Renard . PaPrBaG: A machine learning approach for the detection of novel pathogens from NGS data. 7(7):39194. Publisher: Nature Publishing Group. · DOI
  14. Les Dethlefsen , Margaret McFall-Ngai , and David A. Relman . An ecological and evolutionary perspective on human–microbe mutualism and disease. 449(7164):811–818. Publisher: Nature Publishing Group. · DOI · Paper page
  15. Juliana DiGiacomo , Christopher McKay , and Alfonso Davila . ThermoBase: A database of the phylogeny and physiology of thermophilic and hyperthermophilic organisms. 17(17):e0268253. · DOI
  16. Ahmed Elnaggar , Michael Heinzinger , Christian Dallago , Ghalia Rehawi , Yu Wang , Llion Jones , Tom Gibbs , Tamas Feher , Christoph Angerer , Martin Steinegger , Debsindhu Bhowmik , and Burkhard Rost . ProtTrans: Toward understanding the language of life through self-supervised learning. 44(10):7112–7127. Conference Name: IEEE Transactions on Pattern Analysis and Machine Intelligence. · DOI · Paper page
  17. Alfred S. Evans . Limitations of the henle—koch postulates. In Alfred S. Evans , editor, Causation and Disease: A Chronological Journey, pages 123–146. Springer US. · DOI
  18. Charles Feldman and Ronald Anderson . Meningococcal pneumonia: a review. 11(11):3. · DOI
  19. Alfred Ferrer Florensa , Jose Juan Almagro Armenteros , Henrik Nielsen , Frank Møller Aarestrup , and Philip Thomas Lanken Conradsen Clausen. SpanSeq: similarity-based sequence data splitting method for improved development and assessment of deep learning projects. 6(6):qae106. · DOI
  20. Henrik Hasman , Dhany Saputra , Thomas Sicheritz-Ponten , Ole Lund , Christina Aaby Svendsen , Niels Frimodt-Møller , and Frank M. Aarestrup . Rapid whole-genome sequencing for detection and characterization of microor-ganisms directly from clinical samples. 52(1):139–146. · DOI
  21. Tracy H. Hazen , Jane M. Michalski , Sharon M. Tennant , and David A. Rasko . Genomic diversity of non-diarrheagenic fecal escherichia coli from children in sub-saharan africa and south asia and their relatedness to diarrheagenic e. coli. 14(14):1400. Publisher: Nature Publishing Group. · DOI
  22. U. Hobohm , M. Scharf , R. Schneider , and C. Sander . Selection of representative protein data sets. 1(3):409–417. · DOI
  23. Matthew Holden , Lisa Crossman , Ana Cerdeño-Tárraga , and Julian Parkhill . Pathogenomics of non-pathogens. 2(2):91–91. Publisher: Nature Publishing Group. · DOI
  24. Doug Hyatt , Gwo-Liang Chen , Philip F. LoCascio , Miriam L. Land , Frank W. Larimer , and Loren J. Hauser . Prodigal: prokaryotic gene recognition and translation initiation site identification. 11(11):119. · DOI
  25. Marie Louise Jespersen , Patrick Munk , Joachim Johansen , Rolf Sommer Kaas , Henry Webel , Håkan Vigre , Henrik Bjørn Nielsen , Simon Rasmussen , and Frank M. Aarestrup . Global within-species phylogenetics of sewage microbes suggest that local adaptation shapes geographical bacterial clustering. 6(1):1–9. Publisher: Nature Publishing Group. · DOI
  26. Alyssa G. Kent , Albert C. Vill , Qiaojuan Shi , Michael J. Satlin , and Ilana Lauren Brito . Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial hi-c. 11(11):4379. Publisher: Nature Publishing Group.
  27. Viacheslav Khomenko , Oleg Shyshkov , Olga Radyvonenko , and Kostiantyn Bokhan . Accelerating recurrent neural network training using sequence bucketing and multi-GPU data parallelization. In 2016 IEEE First International Conference on Data Stream Mining & Processing (DSMP), pages 100–103. IEEE. · DOI
  28. Preeti Koli , Sudhanshu Sudan , David Fitzgerald , Sankar Adhya , and Sudeshna Kar . Conversion of commensal escherichia coli k-12 to an invasive form via expression of a mutant histone-like protein. 2(2):e00182–11. · DOI
  29. Weizhong Li and Adam Godzik . Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. 22(13):1658–1659. · DOI
  30. Bo Liu , Dandan Zheng , Siyu Zhou , Lihong Chen , and Jian Yang . VFDB 2022: a general classification scheme for bacterial virulence factors. 50:D912–D917. · DOI
  31. B. W. Matthews . Comparison of the predicted and observed secondary structure of t4 phage lysozyme. 405(405):442– 451. · DOI · Paper page
  32. Leland McInnes , John Healy , and Steve Astels . hdbscan: Hierarchical density based clustering. 2(2):205. · DOI · Paper page
  33. Pierre-Olivier Méthot and Samuel Alizon . What is a pathogen? toward a process view of host-parasite interactions. 5(8):775–785. · DOI
  34. Shaked Naor-Hoffmann , Dina Svetlitsky , Neta Sal-Man , Yaron Orenstein , and Michal Ziv-Ukelson . Predicting the pathogenicity of bacterial genomes using widely spread protein families. 23(23):253. · DOI
  35. National Research Council (US) Committee on Scientific Milestones for the Development of a Gene Sequence-Based Classification System for the Oversight of Select Agents. Challenges of predicting pathogenicity from sequence. In Sequence-Based Classification of Select Agents: A Brighter Line. National Academies Press (US).
  36. Nuala A. O’Leary , Mathew W. Wright , J. Rodney Brister , Stacy Ciufo , Diana Haddad , Rich McVeigh , Bhanu Rajput , Barbara Robbertse , Brian Smith-White , Danso Ako-Adjei , Alexander Astashyn , Azat Badretdin , Yiming Bao , Olga Blinkova , Vyacheslav Brover , Vyacheslav Chetvernin , Jinna Choi , Eric Cox , Olga Ermolaeva , Catherine M. Farrell , Tamara Goldfarb , Tripti Gupta , Daniel Haft , Eneida Hatcher , Wratko Hlavina , Vinita S. Joardar , Vamsi K. Kodali , Wenjun Li , Donna Maglott , Patrick Masterson , Kelly M. McGarvey , Michael R. Murphy , Kathleen O’Neill , Shashikant Pujar , Sanjida H. Rangwala , Daniel Rausch , Lillian D. Riddick , Conrad Schoch , Andrei Shkeda , Susan S. Storz , Hanzhen Sun , Francoise Thibaud-Nissen , Igor Tolstoy , Raymond E. Tully , Anjana R. Vatsan , Craig Wallin , David Webb , Wendy Wu , Melissa J. Landrum , Avi Kimchi , Tatiana Tatusova , Michael DiCuccio , Paul Kitts , Terence D. Murphy , and Kim D. Pruitt . Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. 44:D733–D745. · DOI · Paper page
  37. Jiao Pan , Weiyi Li , Jiahao Ni , Kun Wu , Iain Konigsberg , Caitlyn E. Rivera , Clayton Tincher , Colin Gregory , Xia Zhou , Thomas G. Doak , Heewook Lee , Yan Wang , Xiang Gao , Michael Lynch , and Hongan Long . Rates of mutations and transcript errors in the foodborne pathogen salmonella enterica subsp. enterica. 39(39):msac081. · DOI
  38. 10.1128/microbiolspec.VMBF–0027–2015 · DOI
  39. C. Sabia , S. de Niederhäusern , P. Messi , G. Manicardi , and M. Bondi . Bacteriocin-producing Enterococcus casseliflavus IM 416k1, a natural antagonist for control of Listeria monocytogenes in italian sausages (“cacciatore”). 87(1):173–179. · DOI
  40. Yu Sato , Kenji Okano , Hiroyuki Kimura , and Kohsuke Honda . TEMPURA: Database of growth TEMPeratures of usual and RAre prokaryotes. 35(3). · DOI
  41. Herbert Schmidt and Michael Hensel . Pathogenicity islands in bacterial pathogenesis. 17(1):14–56. Publisher: American Society for Microbiology. · DOI · Paper page
  42. Martin Steinegger and Johannes Söding . MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets. 35(11):1026–1028. Publisher: Nature Publishing Group. · DOI · Paper page
  43. Baris E. Suzek , Hongzhan Huang , Peter McGarvey , Raja Mazumder , and Cathy H. Wu . UniRef: comprehensive and non-redundant UniProt reference clusters. 23(10):1282–1288. Publisher: Oxford Academic. · DOI · Paper page
  44. Toon Swings , Bram Van den Bergh , Sander Wuyts , Eline Oeyen , Karin Voordeckers , Kevin J Verstrepen , Maarten Fauvart , Natalie Verstraeten , and Jan Michiels . Adaptive tuning of mutation rates allows fast response to lethal stress in escherichia coli. 6:e22939. · DOI
  45. Peter J. Turnbaugh , Ruth E. Ley , Micah Hamady , Claire M. Fraser-Liggett , Rob Knight , and Jeffrey I. Gordon . The human microbiome project. 449(7164):804–810. Publisher: Nature Publishing Group. · DOI · Paper page
  46. J W Wilson , M J Schurr , C L LeBlanc , R Ramamurthy , K L Buchanan , and C A Nickerson . Mechanisms of bacterial pathogenicity. 78(918):216–224. · DOI
  47. Yusuke Yoshino . Enterococcus casseliflavus infection: A review of clinical features and treatment. 16:363–368. · DOI

Metadata

Authors
Ferrer Florensa, A., Almagro Armenteros, J. J., Kaas, R. S., Conradsen Clausen, P. T. L., Nielsen, H., Rost, B., & Aarestrup, F. M.
Affiliations
  • Research Group for Genomic Epidemiology, Technical University of Denmark, Kongens Lyngby, Denmark
  • Informatics and Predictive Sciences Research, Bristol Myers Squibb Company, Sevilla, Spain
  • Technical University of Denmark (DK)
  • Technical University of Munich (DE)
Venue
Bioinformatics
Publisher
openRxiv
Published
2025-04-18
Volume
42
Issue
5
ISSN
1367-4803 (ISSN-L)
OpenAlex
W7139978436
Cited by
50
References
1
Citations by year
2026: 41 · 2025: 9
FWCI
84.74
Type
journal article
Language
en
Open access
Locations
  • Bioinformatics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
Funders
  • European High Performance Computing Joint Undertaking
  • Bristol-Myers Squibb
  • European Commission (874735, HORIZON2020)
  • Novo Nordisk Fonden (NNF26SA0109818)
  • National Institute of Allergy and Infectious Diseases (U24AI183840)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
protein language models, novel bacterial taxa, virulence factors, vaccine targets, infection site, microbial antagonism, emerging pathogens
MeSH terms
Bacteria, Humans, Software, Genome, Bacterial, Computational Biology, Genomics, Virulence Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review