Search bioRxivSearch

bioRxiv · 10.1101/2020.03.02.972778

A Novel Riboswitch Classification based on Imbalanced Sequences achieved by Machine Learning

Abstract

Riboswitch, a part of mRNA (50-250nt in length), has two main classes: aptamer and expression platform. One of the main challenges raised during the classification of riboswitch is imbalanced data. That is a circumstance in which the records of a dataset of one group are very small compared to the others. Such circumstances lead classifier to ignore minority group and emphasize on majority class, that resulting with a skewed classification. We considered sixteen riboswitch families, to be in accord with recent riboswitch classification work, that contain imbalanced dataset ranging from 4,826 instances (RF00174) to 39 (RF01051) instances. The dataset was divided into training and test set using new developed pipeline. From 5460 k-mers, 156 features were produced calculated based on CfsSubsetEval and BestFirst. Statistically tested result was significantly difference between balanced and imbalanced dataset (p < 0.05). Besides, each algorithm also showed a significant difference in sensitivity, specificity, accuracy, and macro F-score when used in both groups (p < 0.05). Several k-mers clustered from heat map were discovered to have biological functions and motifs at the different positions like interior loops, terminal loops and helices. They were validated to have a biological function and some are riboswitch motifs. The analysis has discovered the importance of solving the challenges of majority bias analysis and overfitting. Presented results were generalized evaluation of both balanced and imbalanced models, which implies their ability of classifying novel riboswitches. The scientific community can use python source code at https://github.com/Seasonsling/riboswitch, which can contribute to the process of developing software packages. Author SummaryMachine learning application has been used in many ways in bioinformatics and computational biology. Its use in riboswitch classification is still limited and existing attempt showed challenges due to imbalanced dataset. Algorithms classify dataset with majority and minority group, but they tend to ignore minority group and emphasize on majority class, consequential return a skewed classification We used new pipeline including SMOTE for balancing datasets that showed better classified riboswitch as well as improved performance of algorithms selected. Statistically significant difference observed between balanced and imbalanced in sensitivity, specificity, accuracy and F-score, this proved balanced dataset better for classification of riboswitch. Biological functions and motif search of k-mers in riboswitch families revealed their presence in interior loops, terminal loops and helices, some of the k-mers were reported to be riboswitch motifs of aptamer domains and critical for metabolite binding. The pipeline can be used in machine learning and deep learning study in other domains of bioinformatics and computational biology suffering from imbalanced dataset. Finally, scientific community can use python source code, the work done and flow to develop packages.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Beyene, S. S., Ling, T., Ristevski, B., Chen, M.. 2020-03-02. A Novel Riboswitch Classification based on Imbalanced Sequences achieved by Machine Learning. https://doi.org/10.1101/2020.03.02.972778

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

KEEP EXPLORING

Related preprints

spatialMET: an open and scalable framework for spatial metabolomics analysis

Mass spectrometry imaging (MSI) enables spatially resolved metabolomics in intact tissue sections, but analysis remains challenging at scale. Existing MSI workflows often require users to combine multiple software tools, while others rely on proprietary vendor software that limits interoperability and reproducibility. To address these challenges, we developed spatialMET, an open-source framework that provides an end-to-end workflow for MSI analysis. spatialMET provides a unified platform for preprocessing, spatial domain detection, and visualization. Downstream analyses include differential abundance testing, spatial autocorrelation and gradient analysis, dimensionality reduction, and correlation network analysis. Spatial domain detection uses hcdist, a C-based hierarchical clustering implementation that substantially reduces runtime and memory use relative to existing R-based approaches. spatialMET can be run through an interactive R Shiny application or as a standalone command-line workflow for larger datasets or high-performance computing environments. Applied to mouse small cell lung cancer MALDI-MSI data containing 284,673 pixels, spatialMET identified tumor-associated, stromal, and adjacent lung spatial domains that aligned with matched histology. Differential abundance analysis identified 117 m/z features that differed between tumor and stromal regions, while spatial autocorrelation analyses revealed spatially structured abundance patterns. Applying spatialMET to mouse lung adenocarcinoma data from an entire lung lobe containing 338,477 pixels further demonstrated scalability and captured spatial heterogeneity across tumor and surrounding lung tissue. In summary, spatialMET provides a scalable, open-source framework for end-to-end spatial metabolomics analysis, and it is distributed as a Docker container for reproducible deployment. Source code and installation instructions are available at https://github.com/biodatalab/spatialMET.

bioinformatics

Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

bioinformatics

An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry.

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single cell RNA sequencing data. We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes. A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work. Application of the proposed framework to single cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data. Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype and phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.

bioinformatics