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

Abstract

40Background 41 Mitochondria produce cellular energy in the form of ATP and are involved in various 42 metabolic and signaling processes. However, the cellular requirements for 43 mitochondria are different depending on cell type, cell state or organism. Information 44 on the expression dynamics of genes with mitochondrial functions (mito-genes) is 45 embedded in publicly available transcriptomic or proteomic studies and the variety of 46 available datasets enables us to study the expression dynamics of mito-genes in many 47 different cell types, conditions and organisms. Yet, we lack an easy way of extracting 48 these data for gene groups such as mito-genes. 49 50 Results 51 Here, we introduce the web-based visual data mining platform mitoXplorer, which 52 systematically integrates expression and mutation data of mito-genes. The central part 53 of mitoXplorer is a manually curated mitochondrial interactome containing ~1200 54 genes, which we have annotated in 35 different mitochondrial processes. This 55 mitochondrial interactome can be integrated with publicly available transcriptomic, 56 proteomic or mutation data in a user-centric manner. A set of analysis and visualization 57 tools allows the mining and exploration of mitochondrial expression dynamics and 58 mutations across various datasets from different organisms and to quantify the 59 adaptation of mitochondrial dynamics to different conditions. We apply mitoXplorer to 60 quantify expression changes of mito-genes of a set of aneuploid cell lines that carry 61 an extra copy of chromosome 21. mitoXplorer uncovers remarkable differences in the 62 regulation of the mitochondrial transcriptome and proteome due to the dysregulation 63 of the mitochondrial ribosome in retinal pigment epithelial trisomy 21 cells which 64 results in severe defects in oxidative phosphorylation. 65 3 66Conclusions 67 We demonstrate the power of the visual data mining platform mitoXplorer to explore 68 expression data in a focused and detailed way to uncover underlying potential 69 mechanisms for further experimental studies. We validate the hypothesis-creating 70 power of mitoXplorer by testing predicted phenotypes in trisomy 21 model systems. 71 MitoXplorer is freely available at http://mitoxplorer.ibdm.univ-mrs.fr. MitoXplorer does 72 not require installation nor programming knowledge and is web-based. Therefore, 73 mitoXplorer is accessible to a wide audience of experimental experts studying 74 mitochondrial dynamics. 75 76 77 4

The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

“…Because the KEGG, SPIA, and GO term analyses described above hinted, in line with the literature, toward mitochondria being a key player in both damage 35,36 and preconditioning, 37,38 we used mitoXplorer 24 to obtain a more detailed view on mitochondrial processes. Preconditioning via CR affected mitochondrial pathways much more than HP (Supplemental Figure 12).…”

“…mitoXplorer was used to analyze and visualize mitochondrial expression dynamics. 24 For visualization of the data, access http://mitoxplorer.ibdm.univ-mrs.fr/, then go to "analysis," choose "Mouse" as organism and select project "Kidney_Injury" to view the data.…”

Stable Isotope Labeling of Amino Acids in Flies (SILAF) Reveals Differential Phosphorylation of Mitochondrial Proteins Upon Loss of OXPHOS Subunits

“…p value < 0.01), corresponding to 12.5% of the total detected proteome, including nonmitochondrial background ( supplemental Table S5 ). Using a curated set of Dm mitochondrial proteins ( 20 ), our data set covered 75.3% of the mitoproteome ( supplemental Fig. S4 B ).…”

“…Adjusted p values for plotting were calculated as FDR with limma moderated t test ( 19 ), which is part of the limma package version 3.38.3. The Dm -specific MitoXplorer ( 20 ) library was used to annotate mitochondrial proteins and the functional processes they are related to.…”

OmicsVolcano: Software for intuitive visualization and interactive exploration of high-throughput biological data

“…Specific information about mitochondrial processes was based on our previous studies ( Kühl et al. 2017 ), MitoXplorer ( Yim et al. 2019 ) and combined with MitoCarta 2.0 ( Calvo et al.…”