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Record W4207072842 · doi:10.1093/ecco-jcc/jjab232.832

P711 Stool microbiome communities predict remission in pediatric Crohn’s disease patients even after start of treatment

2022· article· en· W4207072842 on OpenAlexaff
Charlotte M. Verburgt, Katherine A. Dunn, Joseph P. Bielawski, Anthony Otley, Melvin B. Heyman, Whitney M. Sunseri, Dror S. Shouval, Arie Levine, Tim de Meij, Jeffrey S. Hyams, Lee A. Denson, Subra Kugathasan, Marc A. Benninga, Wouter J. de Jonge, Johan Van Limbergen

Bibliographic record

VenueJournal of Crohn s and Colitis · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsDalhousie University
Fundersnot available
KeywordsCohortInternal medicineDiseaseMicrobiomeMedicineAmplicon sequencingAmplicon16S ribosomal RNABiologyBioinformaticsPolymerase chain reactionGenetics

Abstract

fetched live from OpenAlex

Abstract Background Early relapse in children with Crohn’s Disease (CD) after reaching remission is associated with a more severe disease course that significantly impairs quality of life. We have previously shown that a Bayesian approach predicted clinical course in children with CD following the first year after diagnosis with high accuracy when ensuring samples were truly treatment-naïve. Here, we aimed to assess the impact on the accuracy when taking a broader timeframe of stool collection to baseline, in order to facilitate use in clinical trials and eventually daily practice. Methods We selected de novo paediatric CD patients with PCDAI>10 from the RISK cohort with baseline stool samples within 14 days after start of induction treatment. We assessed if they sustained remission at 12 months (PCDAI≤10). Using QIIME2 sequences were demultiplexed, joined, and denoised (deblur) to obtain amplicon sequence variants (ASVs). The ASVs were classified (classify-sklearn) using a pre-trained SILVA database. We used hierarchical Bayesian model for microbial community structure (BioMiCo), previously trained on treatment-naïve stool samples to predict treatment outcomes at 6 months according to baseline gut microbiome differences. Results Patient metadata and 16S rRNA amplicon data were available from 197 stool samples of newly diagnosed paediatric CD patients as part of the RISK cohort. Previous analysis of 42 truly treatment-naïve samples lead to prediction of samples in patients maintaining remission without early treatment escalation and those that did not in 81% and 75% (AUC=0.79). In this analysis, we selected 13 samples of children with PCDAI that were taken within 14 days after start of induction therapy. PCDAI varied from 15–47.5 at baseline. Therapy regimens started within the first 14 days were EEN, 5ASA, corticosteroids, immunomodulators and antibiotics. The Bayesian model predicted 12-month outcome of patients that maintained remission with a positive predictive value of 75% and negative predictive value of 60% (AUC 0.76). Conclusion Using treatment-naïve faecal samples only, a Bayesian approach predicted clinical course in treatment-naïve children with CD over the first year after diagnosis with high accuracy. When taking a broader timeframe of stool collection after start of treatment, the accuracy of the model decreased only slightly. Further exploration of microbiome signatures and potential use in practice should therefore emphasize the importance of treatment naivety of samples, but not necessarily rule them out for prediction of treatment outcome.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.006
GPT teacher head0.215
Teacher spread0.209 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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".

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Citations1
Published2022
Admission routes1
Has abstractyes

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