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Record W4401970743 · doi:10.1101/2024.08.26.609770

Characterizing features affecting local ancestry inference performance in admixed populations

2024· preprint· en· W4401970743 on OpenAlexaff
Jessica Honorato‐Mauer, Nirav N. Shah, Adam X. Maihofer, Clement C. Zai, Síntia Belangero, Caroline M. Nievergelt, Marcos Santoro, Elizabeth G. Atkinson

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of Toronto
FundersNational Institute of Mental HealthFundação de Amparo à Pesquisa do Estado de São Paulo
KeywordsInferenceEvolutionary biologyR packageComputer scienceGeographyGenealogyArtificial intelligenceBiologyStatisticsMathematicsHistory

Abstract

fetched live from OpenAlex

In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using Local Ancestry Inference (LAI). Accurate LAI is crucial to ensure downstream analyses reflect the genetic ancestry of research participants accurately. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries - African (AFR), Amerindigenous (AMR), and European (EUR). Simulating LD-informed admixed haplotypes under a variety of 2 and 3-way admixture models, we implemented a standard LAI pipeline, testing three reference panel compositions to quantify their overall and ancestry-specific accuracy. We examined LAI miscall frequencies and true positive rates (TPR) across simulation models and continental ancestries. AMR tracts have notably reduced LAI accuracy as compared to EUR and AFR tracts in all comparisons, with TPR means for AMR ranging from 88-94%, EUR from 96-99% and AFR 98-99%. When LAI miscalls occurred, they most frequently erroneously called European ancestry in true Amerindigenous sites. Using a reference panel well-matched to the target population, even with a lower sample size, LAI produced true-positive estimates that were not statistically different from a high sample size but mismatched reference, while being more computationally efficient. While directly responsive to admixed Latin American cohort compositions, these trends are broadly useful for informing best practices for LAI across other admixed populations. Our findings reinforce the need for inclusion of more underrepresented populations in sequencing efforts to improve reference panels.

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)0.030
metaresearch head score (Gemma)0.105
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.030
Threshold uncertainty score0.158

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0300.105
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.002
Scholarly communication0.0020.002
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.024
GPT teacher head0.273
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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
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

Citations1
Published2024
Admission routes1
Has abstractyes

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