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Variant identification and interpretation

2023· article· en· W4387877932 on OpenAlexaff
Jorge David Mendez-Rios

Bibliographic record

VenueGenetics and Clinical Genomics · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsCentre hospitalier de l'Université Laval
Fundersnot available
KeywordsHumanitiesPhilosophy

Abstract

fetched live from OpenAlex

The process of variant identification by molecular technologies, through sequencing or array-based methods, is a complex process that requires protocols, quality controls, and technical and clinical knowledge. The complexity of the process does not end with the identification of a genomic variant, but molecular geneticists and clinicians must have sufficient knowledge and experience to interpret the finding and suggest the impact that this variant may or may not have on the patient.Interpretation is not an isolated exercise, but requires repetitive review and systematic review of the available literature on the variant in question. It also requires knowledge of epidemiology, statistics and research methodology to be able to establish a reasonable interpretation with the greatest possible certainty, which is especially important in a clinical setting. Mastering new computer resources such as variant databases (ClinVar, ClinGen, among others) and knowing the population frequency of that variant are additional skills necessary in the exercise of clinical molecular diagnosis. For this reason, in this issue we are pleased to present three clinical cases focused on molecular diagnostics: a case of Allan-Herndon-Dudley Syndrome, another on familial hypercholesterolemia, and finally, a third clinical case on Pitt-Hopkins Syndrome. The three present different approaches, perspectives, and conclusions, allowing us to see the methodologies already implemented in our region. We also present an article on pain and its genetic basis, putting into perspective the variability of perception of each individual to pain stimuli, which may depend on genetic, epigenetic and environmental factors.This issue shows our regional efforts to carry out molecular diagnostics and precision medicine, which are already a reality in our countries, and at the same time, we share knowledge and experiences, which will allow us to document the advances in this discipline of Genetics and Clinical Genomics. Once again, we thank you, our reader, for appreciating this group effort, and we invite you to participate in this academic exercise in our next issues. We hope you will once again enjoy this second issue we have prepared for you.

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)0.019
metaresearch head score (Gemma)0.081
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.038
Threshold uncertainty score0.128

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0190.081
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0150.005
Science and technology studies0.0020.002
Scholarly communication0.0050.002
Open science0.0050.004
Research integrity0.0030.004
Insufficient payload (model declined to judge)0.0380.017

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 head0.312
Teacher spread0.295 · 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 designNot applicable
Domainnot available
GenreMethods

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

Citations0
Published2023
Admission routes1
Has abstractyes

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