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Record W4327814673 · doi:10.1038/s41467-023-37200-w

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

2023· article· en· W4327814673 on OpenAlexfundno aff
Andre Mu, William P. Klare, Sarah L. Baines, Chi Nam Ignatius Pang, Romain Guérillot, Nichaela Harbison-Price, Nadia Keller, Jonathan J. Wilksch, Nguyen Thi Khanh Nhu, Minh‐Duy Phan, Bernhard Keller, Brunda Nijagal, Dedreia Tull, Saravanan Dayalan, Hwa Huat Charlie Chua, Dominik Skoneczny, Jason Koval, Abderrahman Hachani, Anup D. Shah, Nitika Neha, Snehal Jadhav, Sally R. Partridge, Amanda J. Cork, Kate M. Peters, Olivia M. Bertolla, Stephan Brouwer, Steven J. Hancock, Laura Álvarez-Fraga, David M. P. De Oliveira, Brian M. Forde, Ashleigh Dale, Warasinee Mujchariyakul, Calum J. Walsh, Ian R. Monk, Anna Fitzgerald, Mabel Lum, Carolina Correa-Ospina, Piklu Roy Chowdhury, Robert G. Parton, James J. De Voss, J. B. Beckett, Francois Monty, Jessica McKinnon, Xiaomin Song, J. Stephen, Marie Everest, M. Bellgard, Matthew Tinning, Michael G. Leeming, Dianna M. Hocking, Leila Jebeli, Nancy Wang, Nouri L. Ben Zakour, Serhat A. Yasar, Stefano Vecchiarelli, Tonia Russell, Thiri Zaw, Tyrone Chen, Don Teng, Zena Kassir, Trevor Lithgow, Adam Jenney, Jason N. Cole, Victor Nizet, Tania C. Sorrell, Anton Y. Peleg, David L. Paterson, Scott A. Beatson, Jemma Wu, Mark P. Molloy, Anna Syme, Robert J. A. Goode, Adam Hunter, Grahame Bowland, Nicholas P. West, Marc R. Wilkins, Steven P. Djordjevic, Mark R. Davies, Torsten Seemann, Benjamin P. Howden, Dana Pascovici, Sonika Tyagi, Ralf B. Schittenhelm, David P. De Souza, Malcolm J. McConville, Jonathan R. Iredell, Stuart J. Cordwell, Richard A. Strugnell, Timothy P. Stinear, Mark A. Schembri, Mark J. Walker

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsnot available
FundersInstitute of Infection and ImmunityFaculty of Medicine and Health, University of SydneyMonash Biomedicine Discovery Institute, Monash UniversityNational Institute of Allergy and Infectious DiseasesMedical Research CouncilMurdoch UniversityUniversity of QueenslandMonash UniversityChildren's Medical ResearchUniversity of New South WalesUniversity of Technology SydneyUniversity of SydneyAustralian Cancer Research FoundationSchool of Life and Environmental Sciences, Deakin UniversityNational Health and Medical Research CouncilQueensland University of TechnologyCommonwealth Scientific and Industrial Research OrganisationAustralian GovernmentWellcome TrustUniversity of MelbourneMacquarie University
KeywordsBiologySepsisMicrobiologyBacteriaMetabolomicsKlebsiella pneumoniaeEscherichia coliAntibiotic resistancePathogenOmicsSeptic shockAntibioticsBioinformaticsGeneGeneticsImmunology

Abstract

fetched live from OpenAlex

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.489
Threshold uncertainty score0.405

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.033
GPT teacher head0.318
Teacher spread0.285 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations63
Published2023
Admission routes1
Has abstractyes

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