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Record W3010074221 · doi:10.1073/pnas.1910499117

Metabolic and genetic basis for auxotrophies in Gram-negative species

2020· article· en· W3010074221 on OpenAlex
Yara Seif, Kumari Sonal Choudhary, Ying Hefner, Amitesh Anand, Laurence Yang, Bernhard Ø. Palsson

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrobial Metabolic Engineering and Bioproduction
Canadian institutionsQueen's University
FundersNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesNational Institutes of HealthNovo Nordisk FondenNovo Nordisk
KeywordsIndelBiologyAuxotrophyGeneticsComputational biologyProphageGenomeSingle-nucleotide polymorphismGenotypeGeneBacteriophage

Abstract

fetched live from OpenAlex

Auxotrophies constrain the interactions of bacteria with their environment, but are often difficult to identify. Here, we develop an algorithm (AuxoFind) using genome-scale metabolic reconstruction to predict auxotrophies and apply it to a series of available genome sequences of over 1,300 Gram-negative strains. We identify 54 auxotrophs, along with the corresponding metabolic and genetic basis, using a pangenome approach, and highlight auxotrophies conferring a fitness advantage in vivo. We show that the metabolic basis of auxotrophy is species-dependent and varies with 1) pathway structure, 2) enzyme promiscuity, and 3) network redundancy. Various levels of complexity constitute the genetic basis, including 1) deleterious single-nucleotide polymorphisms (SNPs), in-frame indels, and deletions; 2) single/multigene deletion; and 3) movement of mobile genetic elements (including prophages) combined with genomic rearrangements. Fourteen out of 19 predictions agree with experimental evidence, with the remaining cases highlighting shortcomings of sequencing, assembly, annotation, and reconstruction that prevent predictions of auxotrophies. We thus develop a framework to identify the metabolic and genetic basis for auxotrophies in Gram-negatives.

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.

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)0.001
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 score0.076
Threshold uncertainty score0.144

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 science0.0000.000
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 head0.029
GPT teacher head0.262
Teacher spread0.234 · 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