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Record W4412049114 · doi:10.1016/j.jbi.2025.104873

Accounting for population structure in deep learning models for genomic analysis

2025· article· en· W4412049114 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJournal of Biomedical Informatics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsAlberta Children's HospitalUniversity of Calgary
FundersNational Institute of Mental HealthNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthAlberta InnovatesAlberta Children's Hospital FoundationCalgary Foundation
KeywordsArtificial intelligenceConfoundingDeep learningPopulationComputer scienceMachine learningSingle-nucleotide polymorphismComputational biologyBiologyGenotypeGeneticsStatisticsMedicineMathematicsGene

Abstract

fetched live from OpenAlex

BACKGROUND: Deep learning methods are becoming increasingly popular for genotype analyses in recent years. In conventional genomic analyses, it is important to account for confounders to avoid biasing the results. Genetic relatedness is one of the most common confounders in conventional genomic analyses and there is a general consensus that it should be considered in the analysis to prevent distant levels of common ancestry from affecting the identification of causal variants. In contrast, genetic relatedness is not considered or ignored in many of the recently published deep learning models. OBJECTIVE: This study investigates whether the omission of genetic relatedness in deep learning models, common in recent literature, introduces confounding effects similar to those observed in conventional genomic analyses, particularly due to ancestry-related variants. METHODS: We developed and used a deep learning model to perform classifications based on single nucleotide polymorphism data from simulated and real-world datasets to examine whether population structure is confounding the model and potentially causing shortcut learning. RESULTS: The results of this study suggest that population structure may not significantly affect the performance of the deep learning model. However, explainable AI revealed notable differences in the focus between the confounded and unconfounded models when examining SNP feature importance. CONCLUSION: While population structure may not heavily affect model performance, it is important to reduce the models' capabilities of shortcut learning when designing deep learning models for analyzing genomic datasets, by using ancestry-related variants over potentially relevant biomarkers of the disease or disorder in question. The code used to perform these analyses can be found at: https://github.com/notTrivial/populationStructure.

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.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.419
Threshold uncertainty score0.238

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 head0.011
GPT teacher head0.288
Teacher spread0.277 · 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