Search bioRxiv⌕ Search

bioRxiv · 10.1101/431734

Efficient feature selection on gene expression data: Which algorithm to use?

Abstract

BackgroundFeature selection seeks to identify a minimal-size subset of features that is maximally predictive of the outcome of interest. It is particularly important for biomarker discovery from high-dimensional molecular data, where the features could correspond to gene expressions, Single Nucleotide Polymorphisms (SNPs), proteins concentrations, e.t.c. We evaluate, empirically, three state-of-the-art, feature selection algorithms, scalable to high-dimensional data: a novel generalized variant of OMP (gOMP), LASSO and FBED. All three greedily select the next feature to include; the first two employ the residuals re-sulting from the current selection, while the latter rebuilds a statistical model. The algorithms are compared in terms of predictive performance, number of selected features and computational efficiency, on gene expression data with either survival time (censored time-to-event) or disease status (case-control) as an outcome. This work attempts to answer a) whether gOMP is to be preferred over LASSO and b) whether residual-based algorithms, e.g. gOMP, are to be preferred over algorithms, such as FBED, that rely heavily on regression model fitting.\n\nResultsgOMP is on par, or outperforms LASSO in all metrics, predictive performance, number of features selected and computational efficiency. Contrasting gOMP to FBED, both exhibit similar performance in terms of predictive performance and number of selected features. Overall, gOMP combines the benefits of both LASSO and FBED; it is computationally efficient and produces parsimonious models of high predictive performance.\n\nConclusionsThe use of gOMP is suggested for variable selection with high-dimensional gene expression data, and the target variable need not be restricted to time-to-event or case control, as examined in this paper.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tsagris, M., Papadovasilakis, Z., Lakiotaki, K., Tsamardinos, I.. 2018-10-03. Efficient feature selection on gene expression data: Which algorithm to use?. https://doi.org/10.1101/431734

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

KEEP EXPLORING

Related preprints

scRM: A single-cell foundation model trained on scRNA-seq reads

To our knowledge, scRM is the first single-cell foundation model trained on sequencing reads, demonstrating that raw data pretraining is not only feasible but competitive at a fraction of the computational cost. We anticipate that scaling this framework and exploring alternative architectures will unlock biological information inaccessible to count models and extend the dataset-specific pretraining it already makes possible. The source code is available at https://github.com/altos-labs/scRM.

bioinformatics↗

Local fractal dimension as an indicator of functional reorganization in molecular interaction networks

Changes in protein abundance incompletely describe how molecular perturbations reshape cellular organization. Here we introduce DIFFRACT, a framework that integrates quantitative proteomics with protein-protein interaction networks to identify reorganization through changes in local fractal dimension. Molecular associations define effective distances between connected proteins, allowing the geometry of their surrounding network neighborhoods to be compared across conditions. Analyses across four organisms (E. coli, A. thaliana, C. elegans, and H. sapiens) and three interaction resources (STRING, BioGRID, and IntAct) establish heterogeneous local scaling, while controlled perturbations demonstrate sensitivity to regional changes and invariance to uniform distance rescaling. Applied to RAVER1-deficient A549 cells, DIFFRACT identifies components associated with established RNA-regulatory functions and candidate roles in tRNA biology, mitochondrial organization and ciliogenesis. Selected RNA-regulatory and ciliary themes are not significantly enriched by abundance-ranked gene set analysis, supporting complementary information from network geometry. Selected functional annotations also recur in HEK293T cells. Guided by the ciliary predictions, we show that RAVER1 depletion increases the proportion of ciliated A549 cells 2.57-fold and increases cilium length. DIFFRACT thus connects changes in molecular network geometry to experimentally testable biological responses, extending the interpretation of proteomic perturbations beyond differential abundance.

bioinformatics↗

Peripheral Exercise Transcriptomes Do Not Converge on Glutamatergic or Neuroinflammatory Signatures: A Cross-Platform Meta-Analysis

Executive dysfunction following physical overtraining has been linked to glutamatergic dysregulation in the lateral prefrontal cortex (LPFC), but whether this central mechanism is reflected in peripheral gene expression is unknown. This study tested whether peripheral transcriptomic responses to exercise converge on the glutamatergic or neuroinflammatory pathways implicated in LPFC dysfunction. Three publicly available GEO datasets spanning skeletal muscle, whole blood, and circulating neutrophils were analyzed across four exercise groups using limma, with a discovery threshold of nominal p < 0.05 and absolute log2 fold change above 0.5. Differential expression analysis identified 7,311 unique differentially expressed genes (DEGs) across the four contrasts, but overlap between datasets was limited: 7 genes were shared between skeletal muscle and blood, 38 between skeletal muscle and the GSE43856 contrasts, and 90 between blood and the GSE43856 contrasts, with none significant across all three studies. Gene Ontology and KEGG enrichment of the DEG union identified ribonucleoprotein complex biogenesis, ribosome biogenesis, protein folding, and T cell activation as the dominant biological processes; no glutamatergic or neuroinflammatory terms reached significance. Cross-tissue concordance between skeletal muscle and blood was absent (r = 0). Effect sizes among the genes driving the top enriched pathways were dominated by ribosomal proteins, heat shock proteins, and translation initiation factors rather than glutamate receptors or transporters. These findings indicate that peripheral transcriptomic responses to exercise are tissue-specific and dominated by proteostasis, translational, and immune programs rather than glutamatergic signaling. Direct assessment of central nervous system tissue or fluid-based glutamatergic biomarkers may be required to link overtraining-induced fatigue to LPFC dysfunction.

bioinformatics↗