Improving mass-univariate analysis of neuroimaging data by modelling important unknown covariates: Application to Epigenome-Wide Association Studies
Bibliographic record
Abstract
Statistical inference on neuroimaging data is often conducted using a mass-univariate model, equivalent to fitting a linear model at every voxel with a known set of covariates. Due to the large number of linear models, it is challenging to check if the selection of covariates is appropriate and to modify this selection adequately. The use of standard diagnostics, such as residual plotting, is clearly not practical for neuroimaging data. However, the selection of covariates is crucial for linear regression to ensure valid statistical inference. In particular, the mean model of regression needs to be reasonably well specified. Unfortunately, this issue is often overlooked in the field of neuroimaging. This study aims to adopt the existing Confounder Adjusted Testing and Estimation (CATE) approach and to extend it for use with neuroimaging data. We propose a modification of CATE that can yield valid statistical inferences using Principal Component Analysis (PCA) estimators instead of Maximum Likelihood (ML) estimators. We then propose a non-parametric hypothesis testing procedure that can improve upon parametric testing. Monte Carlo simulations show that the modification of CATE allows for more accurate modelling of neuroimaging data and can in turn yield a better control of False Positive Rate (FPR) and Family-Wise Error Rate (FWER). We demonstrate its application to an Epigenome-Wide Association Study (EWAS) on neonatal brain imaging and umbilical cord DNA methylation data obtained as part of a longitudinal cohort study. Software for this CATE study is freely available at http://www.bioeng.nus.edu.sg/cfa/Imaging_Genetics2.html.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.040 | 0.138 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".