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A Molecular Nearest-Neighbours Approach to Diagnosis and Prognosis in Kidney Transplant Biopsies.

2014· article· en· W2771740835 on OpenAlexaff
J. Reeve, Philip F. Halloran

Bibliographic record

VenueTransplantation · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBiological Research and Disease Studies
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsMedicineBiopsyKidney transplantRenal functionCreatinineMedical diagnosisKidneyUnivariate analysisKidney transplantationInternal medicinePathologyMultivariate analysis

Abstract

fetched live from OpenAlex

While assessment of the conventional and molecular phenotype of a biopsy provides diagnostic information, it stops short of providing a sense of what is likely to happen. We used a molecular nearest-neighbours approach to predict diagnoses and prognoses in a series of kidney transplant biopsies-for-cause. We have previously developed univariate molecular classifiers for various kidney pathologies. In the present study, we combined the molecular scores for ABMR, TCMR, rejection, fibrosis, loss of solute carriers, and injury/repair, in a reference set of 538 biopsies. These scores were then reduced into 3-dimensional space via principal components analysis (PCA). As new cases presented, their molecular scores were projected into this space.Figure: No Caption available.The histologic diagnosis of each new sample's 50 nearest neighbours was then obtained, along with their 1- and 3-year survival rates. Three-dimensional Euclidean distance was used to define proximity.Table: No Caption available.The clinical application of the nearest neighbours is illustrated by two cases. Case 1 received a live donor transplant 64 days earlier and had stable but impaired function. The biopsy showed no rejection and relatively little AKI. Most neighbours had been diagnosed with no rejection, and 98% survived to at least one year. Case 2 illustrates a much more troubled kidney, presenting with rising creatinine 9.8 years post transplant and suspected recurrent disease. Many of its nearest neighbours had rejection, with 1- and 3-year survival of 71% and 45% respectively. This illustrates how the nearest neighbours approach, by comparing new patients with a large reference set of similar cases, can provide the clinician with a sense of the impact of these molecular phenotypes. DISCLOSURES:Halloran, P.: Other, Astellas, lecturing, Novartis, lecturing, One Lambda, lecturing.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.093
Threshold uncertainty score0.431

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 science0.0000.000
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 head0.015
GPT teacher head0.262
Teacher spread0.248 · 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 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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Citations0
Published2014
Admission routes1
Has abstractyes

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