arXiv subjects

Boris P Hejblum

Publications and source records attributed to Boris P Hejblum.

3 recordsLinked to original sources

arXiv2022

Post-clustering difference testing: valid inference and practical considerations

Clustering is part of unsupervised analysis methods that consist in grouping samples into homogeneous and separate subgroups of observations also called clusters. To interpret the clusters, statistical hypothesis testing is often used to infer the variables that significantly separate the estimated clusters from each other. However, data-driven hypotheses are considered for the inference process, since the hypotheses are derived from the clustering results. This double use of the data leads traditional hypothesis test to fail to control the Type I error rate particularly because of uncertainty in the clustering process and the potential artificial differences it could create. We propose three novel statistical hypothesis tests which account for the clustering process. Our tests efficiently control the Type I error rate by identifying only variables that contain a true signal separating groups of observations.

stat.ME↗

arXiv2021

Robust and Efficient Optimization Using a Marquardt-Levenberg Algorithm with R Package marqLevAlg

Implementations in R of classical general-purpose algorithms for local optimization generally have two major limitations which cause difficulties in applications to complex problems: too loose convergence criteria and too long calculation time. By relying on a Marquardt-Levenberg algorithm (MLA), a Newton-like method particularly robust for solving local optimization problems, we provide with marqLevAlg package an efficient and general-purpose local optimizer which (i) prevents convergence to saddle points by using a stringent convergence criterion based on the relative distance to minimum/maximum in addition to the stability of the parameters and of the objective function; and (ii) reduces the computation time in complex settings by allowing parallel calculations at each iteration. We demonstrate through a variety of cases from the literature that our implementation reliably and consistently reaches the optimum (even when other optimizers fail), and also largely reduces computational time in complex settings through the example of maximum likelihood estimation of different sophisticated statistical models.

stat.CO↗

arXiv2017

Variance component score test for time-course gene set analysis of longitudinal RNA-seq data

As gene expression measurement technology is shifting from microarrays to sequencing, the statistical tools available for their analysis must be adapted since RNA-seq data are measured as counts. Recently, it has been proposed to tackle the count nature of these data by modeling log-count reads per million as continuous variables, using nonparametric regression to account for their inherent heteroscedasticity. Adopting such a framework, we propose tcgsaseq, a principled, model-free and efficient top-down method for detecting longitudinal changes in RNA-seq gene sets. Considering gene sets defined a priori, tcgsaseq identifies those whose expression vary over time, based on an original variance component score test accounting for both covariates and heteroscedasticity without assuming any specific parametric distribution for the transformed counts. We demonstrate that despite the presence of a nonparametric component, our test statistic has a simple form and limiting distribution, and both may be computed quickly. A permutation version of the test is additionally proposed for very small sample sizes. Applied to both simulated data and two real datasets, the proposed method is shown to exhibit very good statistical properties, with an increase in stability and power when compared to state of the art methods ROAST, edgeR and DESeq2, which can fail to control the type I error under certain realistic settings. We have made the method available for the community in the R package tcgsaseq.

stat.AP↗