bioRxiv Science⌕ Search

bioRxiv · 10.1101/641423

mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations

Abstract

BackgroundMitochondria produce cellular energy in the form of ATP and are involved in various metabolic and signaling processes. However, the cellular requirements for mitochondria are different depending on cell type, cell state or organism. Information on the expression dynamics of genes with mitochondrial functions (mito-genes) is embedded in publicly available transcriptomic or proteomic studies and the variety of available datasets enables us to study the expression dynamics of mito-genes in many different cell types, conditions and organisms. Yet, we lack an easy way of extracting these data for gene groups such as mito-genes.\n\nResultsHere, we introduce the web-based visual data mining platform mitoXplorer, which systematically integrates expression and mutation data of mito-genes. The central part of mitoXplorer is a manually curated mitochondrial interactome containing [~]1200 genes, which we have annotated in 35 different mitochondrial processes. This mitochondrial interactome can be integrated with publicly available transcriptomic, proteomic or mutation data in a user-centric manner. A set of analysis and visualization tools allows the mining and exploration of mitochondrial expression dynamics and mutations across various datasets from different organisms and to quantify the adaptation of mitochondrial dynamics to different conditions. We apply mitoXplorer to quantify expression changes of mito-genes of a set of aneuploid cell lines that carry an extra copy of chromosome 21. mitoXplorer uncovers remarkable differences in the regulation of the mitochondrial transcriptome and proteome due to the dysregulation of the mitochondrial ribosome in retinal pigment epithelial trisomy 21 cells which results in severe defects in oxidative phosphorylation.\n\nConclusionsWe demonstrate the power of the visual data mining platform mitoXplorer to explore expression data in a focused and detailed way to uncover underlying potential mechanisms for further experimental studies. We validate the hypothesis-creating power of mitoXplorer by testing predicted phenotypes in trisomy 21 model systems. MitoXplorer is freely available at http://mitoxplorer.ibdm.univ-mrs.fr. MitoXplorer does not require installation nor programming knowledge and is web-based. Therefore, mitoXplorer is accessible to a wide audience of experimental experts studying mitochondrial dynamics.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yim, A., Koti, P., Bonnard, A., Duerrbaum, M., Mueller, C., Villaveces, J., Gamal, S., Cardone, G., Perocchi, F., Storchova, Z., Habermann, B.. 2019-05-17. mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations. https://doi.org/10.1101/641423

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

KEEP EXPLORING

Related preprints

Deducing splicing events from transcript sets with splicelogic

Long-read RNA sequencing captures a greater proportion of full-length transcripts, enabling more accurate isoform identification, discovery of novel isoforms, and more precise differential transcript usage analysis. However, comparing transcripts, whether between conditions or between sets such as novel and annotated isoforms, yields complex isoform changes that are hard to manipulate, summarize, and visualize. This is compounded by vertical integration of some tools, where downstream analysis depends on the specific output of a particular upstream tool. To address this gap, we have developed splicelogic, an R/Bioconductor package that makes transcript-set comparisons biologically interpretable by turning them into discrete splicing events, such as exon skipping, alternative splice sites, intron retention, and alternative transcription start and end sites. We designed splicelogic to integrate easily with existing RNA-seq workflows and tools. The splicelogic functions are modular, readable, and extensible, making it easy for users to adapt core logic to their own custom scientific questions or novel splicing definitions. By obtaining interpretable splicing events from transcript changes, splicelogic enables downstream analyses, including annotation of RNA-binding protein recognition sites, alongside summary statistics and visualization. The splicelogic package is publicly available and distributed through Bioconductor.

bioinformatics↗

Contrastive Learning Improves Generalization on M2OR Olfactory Binding Dataset

Olfaction-based biosensors stand to have profound impacts in fields such as medical diagnostics, national security, and drug discovery. A promising mode of vapor phase biodetection mimics volatile organic compound-olfactory receptor (VOC-OR) interactions with target-specific protein or peptide probes; however, lack of experimental coverage remains a core bottleneck. Current computational approaches aim to improve prediction of VOC-OR binding to reduce experimental burden, and current machine learning approaches fail to demonstrate a level of generalization that addresses current engineering challenges. Here, using the Molecular to Olfactory Dataset (M2OR) and Insect Olfactory Binding Protein Database (iOBPdb) datasets, data partitioning methods and their performance are evaluated on a neural network and contrastive learning framework on such VOC-OR binding datasets, varying: model training, architecture, and structure of the input data distribution. It was found that holding out certain chemical or proteomic motifs from the training data diminished model performance with a two layer neural network model. The model was able to generalize to state of the art performance (0.88 AUCROC) on every data split by applying a contrastive learning objective defined by shared molecular constituents and a stochastic sampler. This suggests the contrastive objective provides a strong inductive bias for neural networks to predict novel VOC-OR pairs. These findings highlight that model performance on pairwise biological interaction datasets can be inflated through identity leakage from constituent overlap, and emphasize the need for more robust evaluation protocols. Furthermore, we show contrastive regularization mitigates dataset degeneracy through enforcement of compatibility in the models latent geometry that may extend to other binder target-datasets where identity leakage confounds evaluation.

bioinformatics↗

Plate design confounds donor variation and model evaluation in single-cell perturbation screens

Single-cell screens of immune cells from many donors are used to study why individuals respond differently and to benchmark response models. Each donor-perturbation combination typically occupies one well, controls are grouped, and donors share one layout, so technical effects can look biological. Using a 90-cytokine screen, two compound screens, four cohorts and simulations, we show that well effects explain most replicate-control variation in abundant cell types, controls carry a shared offset, and identical control wells differ by hundreds of differentially expressed genes at a standard threshold, about as many as two receptor-negative proteins do. Negative controls, design-aware estimators and perturbation-specific evaluation change the interpretation of four recent analyses. A deep-learning model that scores below a perturbation-agnostic predictor under standard evaluation outperforms a simple baseline on perturbation-specific differences in two of three cell types (significantly in one with stricter controls), but predicts less well the component shared with inert wells.

bioinformatics↗