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Record W3203431640 · doi:10.1101/2021.10.01.462481

Prevalence, persistence, and genetics of antibody responses to protein toxins and virulence factors

2021· preprint· en· W3203431640 on OpenAlexafffund
Julia W. Angkeow, Daniel R. Monaco, Athena Chen, Thiagarajan Venkataraman, Sahana Jayaraman, Cristian Valencia, Brandon Sie, Thomas Liechti, Payam Noroozi Farhadi, Gabriela Funez-dePagnier, Cheryl A. Sherman‐Baust, May Q. Wong, Cynthia L. Sears, Patricia J. Simner, June L. Round, Priya Duggal, Uri Laserson, Theodore S. Steiner, Ranjan Sen, Thomas E. Lloyd, Mario Roederer, Andrew L. Mammen, Randy Longman, Lisa G. Rider, H. Benjamin Larman

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldMedicine
TopicInflammatory Myopathies and Dermatomyositis
Canadian institutionsBC Children's Hospital
FundersNational Institute of General Medical SciencesNational Cancer InstituteNational Institutes of HealthMichael Smith Health Research BCCure JM FoundationNational Institute of Allergy and Infectious DiseasesJohns Hopkins UniversityFrank H. and Eva B. Buck FoundationNational Institute of Environmental Health SciencesLeona M. and Harry B. Helmsley Charitable Trust
KeywordsBiologyVirulenceFlagellinImmune systemVirulence factorAntibodyMicrobiologyGeneticsComputational biologyGene

Abstract

fetched live from OpenAlex

Abstract Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via programmable Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, costeffective approach for multiplexed detection of exposure and response to thousands of microbial protein products. Here we designed and constructed a library of 95,601 56 amino acid peptide tiles spanning a subset of environmental proteins more likely to be associated with immune responses: those with “toxin” or “virulence factor” keyword annotations. PhIP-Seq was used to profile the circulating antibodies of ~1,000 individuals against this “ToxScan” library of 14,430 toxins and virulence factors from 1,312 genera of organisms. In addition to a detailed analysis of six commonly encountered human commensals and pathogens, we study the age-dependent stability of the ToxScan profile and use a genome-wide association study (GWAS) to find that the MHC-II locus modulates the selection of bacterial epitopes. We detect previously described anti-flagellin antibody responses in a Crohn’s disease cohort and identify a novel association between anti-flagellin antibodies and juvenile dermatomyositis (JDM). PhIP-Seq with the ToxScan library provides a new window into exposure and immune responses to environmental protein toxins and virulence factors, which can be used to study human health and disease at cohort scale.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.370
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.017
GPT teacher head0.244
Teacher spread0.227 · 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.

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

Citations4
Published2021
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicInflammatory Myopathies and DermatomyositisFrench-language works237,207