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The commercial genetic testing landscape for Parkinson's disease

2021· article· en· W3206271349 on OpenAlexaff
Lola Cook, Jeanine Schulze, Jennifer Verbrugge, James C. Beck, Karen Marder, Rachel Saunders‐Pullman, Christine Klein, Anna Naito, Roy N. Alcalay, Alexis Brice, Amasi Kumeh, Andrew B. West, Andrew Singleton, Birgitt Schüle, Brian Fiske, Carolin Gabbert, Connie Marras, Cornelis Blauwendraat, Courtney Thaxton, Dario R. Alessi, David W. Craig, Edward A. Fon, Emily K. Forbes, Enza Maria Valente, Esther Sammler, Gill Chao, Giulietta Riboldi, Houda Zghal Elloumi, Ignácio F. Mata, Jamie Fong, Jean‐Christophe Corvol, Joshua Shulman, Judith Peterschmitt, Katja Lohmann, Kelly Nudelman, Lara M. Lange, Mark Cookson, Martha Nance, Matthew J. Farrer, Melina Grigorian, Michael A. Schwarzschild, Niccolò E. Mencacci, Owen A. Ross, Pramod K. Mistry, Priscila D. Hodges, Rachel Blake, S. Pablo Sardi, Sali M.K. Farhan, Samuel P. Strom, Shalini Padmanabhan, Shruthi Mohan, Simonne Longerich, Susanne A. Schneider, Suzanne Lesage, Tanya Bardakjian, Tatiana Foroud, Thomas Courtin, Thomas F. Tropea, Yunlong Liu, Ziv Gan‐Or, Ali Shalash, Anne Hall, Avner Thaler, Carolyn M. Sue, Deborah Mascalzoni, Deborah Raymond, Emilia Gatto, Gian Pal, Inke R. König, Ivana Novaković, Marcelo Merello, Mehri Salari, Nobutaka Hattori, Oksana Suchowersky, Soraya Bardien, Sun Ju Chung, T. Simuni, Timothy Lynch, Vincenzo Bonifati

Bibliographic record

VenueParkinsonism & Related Disorders · 2021
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsUniversity of AlbertaMcGill UniversityMontreal Neurological Institute and HospitalUniversity of Toronto
FundersNational Center for Advancing Translational SciencesNational Institute of Neurological Disorders and StrokeNational Human Genome Research Institute
KeywordsGenetic testingParkinsonismLRRK2Parkinson's diseaseMedicineGeneDiseaseGeneticsGenetic heterogeneityBioinformaticsBiologyPathologyPhenotype

Abstract

fetched live from OpenAlex

INTRODUCTION: There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation. METHODS: The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally. RESULTS: We identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial. CONCLUSION: There is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.880
Threshold uncertainty score1.000

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 studies0.0010.000
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 head0.256
Teacher spread0.240 · 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 designOther design
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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Citations29
Published2021
Admission routes1
Has abstractyes

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