SearcharxivSearch

arXiv · 1809.00266

Function-on-Scalar Quantile Regression with Application to Mass Spectrometry Proteomics Data

Abstract

Mass spectrometry proteomics, characterized by spiky, spatially heterogeneous functional data, can be used to identify potential cancer biomarkers. Existing mass spectrometry analyses utilize mean regression to detect spectral regions that are differentially expressed across groups. However, given the inter-patient heterogeneity that is a key hallmark of cancer, many biomarkers are only present at aberrant levels for a subset of, not all, cancer samples. Differences in these biomarkers can easily be missed by mean regression, but might be more easily detected by quantile-based approaches. Thus, we propose a unified Bayesian framework to perform quantile regression on functional responses. Our approach utilizes an asymmetric Laplace working likelihood, represents the functional coefficients with basis representations which enable borrowing of strength from nearby locations, and places a global-local shrinkage prior on the basis coefficients to achieve adaptive regularization. Different types of basis transform and continuous shrinkage priors can be used in our framework. A scalable Gibbs sampler is developed to generate posterior samples that can be used to perform Bayesian estimation and inference while accounting for multiple testing. Our framework performs quantile regression and coefficient regularization in a unified manner, allowing them to inform each other and leading to improvement in performance over competing methods as demonstrated by simulation studies. We also introduce an adjustment procedure to the model to improve its frequentist properties of posterior inference. We apply our model to identify proteomic biomarkers of pancreatic cancer that are differentially expressed for a subset of cancer patients compared to the normal controls, which were missed by previous mean-regression based approaches. Supplementary materials for this article are available online.

Explore related subjects

Keep this discovery

BibTeXRIS

Yusha Liu, Meng Li, Jeffrey S. Morris. 2018-09-01. Function-on-Scalar Quantile Regression with Application to Mass Spectrometry Proteomics Data. https://doi.org/10.1214/19-aoas1319

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Surprise Reduction and Nullification in Bayesian and Inverse Bayesian Inference under Ambiguous Prediction-Error Attribution

In non-stationary environments, prediction errors may signal environmental change or transient outliers, and adaptive systems must track such changes without overreacting to outliers. We distinguish surprise reduction, which updates beliefs to fit observations, from surprise nullification, which weakens constraints imposed by the predictive structure, and formalize both within Bayesian and inverse Bayesian (BIB) inference. Belief and likelihood updates are derived from variational objectives sharing a nullification strength, determined endogenously by minimizing surprise under the candidate post-update predictive distribution. In the Gaussian case, nullification expands belief and likelihood variances by a common factor relative to standard Bayesian updating, leaving the ratio unchanged. BIB thus defers attribution of the prediction error, committing to neither latent-state change nor observation-process uncertainty. The nullification strength is carried over as a candidate and is maintained or released according to the predictive surprise of the next observation. In a mean estimation task with outliers and changepoints, no scanned parameter setting of a Sage-Husa-type adaptive Kalman filter, fixed-strength BIB variant, or belief-forgetting-only variant outperforms BIB in both changepoint tracking and post-outlier stability. An oracle-informed reduced Bayesian model tracks changepoints better but is less stable after outliers. Although BIB maintains no explicit hypotheses about changepoints or outliers, it generates event-dependent dynamics. The learning rate increases after changepoints, whereas after outliers, nullification is released, and this increase is suppressed. Deferring attribution and letting subsequent observations differentiate the responses may constitute a principle of adaptive inference in non-stationary environments.

stat.ME

Generalized Ridge Refitting for the Lasso and Prediction Improvement Bounds

We study a class of Lasso based estimators obtained by applying a quadratic correction on the Lasso equicorrelation set. The penalty matrix determines both the magnitude and geometry of the correction and contains, among other cases, the isotropic Lasso--Ridge correction, least squares refitting, Gram proportional interpolation between the Lasso and least squares, and coordinate specific penalties. We first derive a closed form representation and isolate the positive gain component of the resulting prediction improvement. We then control the remaining stochastic linear term in expectation by localizing the random signed equicorrelation model around a deterministic reference support. This yields a finite sample expectation bound that explicitly accounts for the randomness induced by Lasso model selection. The resulting decomposition provides a unified framework for understanding when Lasso based quadratic corrections can improve prediction.

stat.ME

Discretization in covariate-adaptive randomization: gains and losses

Covariate-adaptive randomization(CAR) is widely implemented in clinical trials to balance prognostic covariates across treatment arms. Continuous covariates are often discretized into strata in practice, yet their consequences are not clearly understood. This paper provides a comprehensive study of the impact of discretization on both the CAR design process and the inferential results thereafter. We establish the asymptotic properties of both imbalance measures and treatment effect estimators under discretized and non-discretized settings. Practical recommendations are given on when and how discretization should be employed. We show that discretization in design is generally recommended, as it enhances robustness against model misspecification. However, if the true model is known, the most efficient strategy is to balance covariates according to that model in the design. The theoretical results are corroborated by extensive simulation studies and an empirical application to a diabetes trial dataset. Together, the results clarify the gains and losses of discretization in CAR and pave the way for learning impact of discretization to other designs and beyond.

stat.ME