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Identifying diagnosis-specific genotype–phenotype associations via joint multitask sparse canonical correlation analysis and classification

2020· article· en· W3043467106 on OpenAlexfundno aff
Lei Du, Fang Liu, Kefei Liu, Xiaohui Yao, Shannon L. Risacher, Junwei Han, Lei Guo, Andrew J. Saykin, Li Shen

Bibliographic record

VenueBioinformatics · 2020
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsnot available
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchH. Lundbeck A/SServierNational Natural Science Foundation of ChinaEisaiChina Postdoctoral Science FoundationNational Institutes of HealthNorthwestern Polytechnical UniversityGenentechIXICONorthern California Institute for Research and EducationNovartis Pharmaceuticals CorporationBioClinicaBiogenPfizerNorthwestern UniversityUniversity of PennsylvaniaUniversity of Southern CaliforniaU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbMeso Scale DiagnosticsAlzheimer's Association
KeywordsCanonical correlationCorrelationPhenotypeJoint (building)GenotypeComputational biologyComputer scienceGeneticsArtificial intelligenceBiologyMathematicsGene

Abstract

fetched live from OpenAlex

MOTIVATION: Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bi-multivariate genotype-phenotype associations. However, most existing SCCA methods are unsupervised, leading to an inability to identify diagnosis-specific genotype-phenotype associations. RESULTS: In this article, we propose a new joint multitask learning method, named MT-SCCALR, which absorbs the merits of both SCCA and logistic regression. MT-SCCALR learns genotype-phenotype associations of multiple tasks jointly, with each task focusing on identifying one diagnosis-specific genotype-phenotype pattern. Meanwhile, MT-SCCALR cannot only select relevant SNPs and imaging QTs for each diagnostic group alone, but also allows the selection of those shared by multiple diagnostic groups. We derive an efficient optimization algorithm whose convergence to a local optimum is guaranteed. Compared with two state-of-the-art methods, MT-SCCALR yields better or similar canonical correlation coefficients and classification performances. In addition, it owns much better discriminative canonical weight patterns of great interest than competitors. This demonstrates the power and capability of MTSCCAR in identifying diagnostically heterogeneous genotype-phenotype patterns, which would be helpful to understand the pathophysiology of brain disorders. AVAILABILITY AND IMPLEMENTATION: The software is publicly available at https://github.com/dulei323/MTSCCALR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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)0.004
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: none
Teacher disagreement score0.594
Threshold uncertainty score0.615

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.125
GPT teacher head0.283
Teacher spread0.158 · 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".

Quick stats

Citations38
Published2020
Admission routes1
Has abstractyes

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