Stabl: sparse and reliable biomarker discovery in predictive modeling of high-dimensional omic data

Abstract

High-content omic technologies coupled with sparsity-promoting regularization methods (SRM) have transformed the biomarker discovery process. However, the translation of computational results into a clinical use-case scenario remains challenging. A rate-limiting step is the rigorous selection of reliable biomarker candidates among a host of biological features included in multivariate models. We propose Stabl, a machine learning framework that unifies the biomarker discovery process with multivariate predictive modeling of clinical outcomes by selecting a sparse and reliable set of biomarkers. Evaluation of Stabl on synthetic datasets and four independent clinical studies demonstrates improved biomarker sparsity and reliability compared to commonly used SRMs at similar predictive performance. Stabl readily extends to double- and triple-omics integration tasks and identifies a sparser and more reliable set of biomarkers than those selected by state-of-the-art early- and late-fusion SRMs, thereby facilitating the biological interpretation and clinical translation of complex multi-omic predictive models. The complete package for Stabl is available online at https://github.com/gregbellan/Stabl.

Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data

“…The analysis identified a set of phenotypic, functional, and spatial TIME features that accurately classified OSCC histological grade, a subset of which validated in an independent cohort. 39 , 40 The late-fusion nature of this modeling approach produced a classification model well balanced between the feature classes and biological compartments.…”

“…2015 30 https://github.com/JinmiaoChenLab/Rphenograph Python 3.9.0 https://www.python.org/ NA Stabl (Python package) Hedou et al. 39 https://github.com/gregbellan/Stabl Steinbock (Docker version) Windhager et al. 2021 32 https://github.com/BodenmillerGroup/steinbock Ilastik 1.4 https://www.ilastik.org/ NA Cellprofiler 4.2.5 https://cellprofiler.org/ NA Other Helios mass cytometer Standard Biotools NA Hyperion imaging system Standard Biotools NA …”

An immune signature of postoperative cognitive decline in elderly patients

“…To identify preoperative single-cell or plasma proteomic features predictive of POCD, we employed Stabl (41), a sparse machine learning method that combines multivariable predictive modeling with a datadriven feature selection process. This method is optimized for analysis of multi-omic datasets, as each omic data layer is first examined individually prior to integration into a unique predictive model.…”