mitoXplorer 3.0, a web tool for exploring mitochondrial dynamics in single-cell RNA-seq data.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

ABSTRACT Mitochondria are important eukaryotic organelles, best known for their function in ATP production and cellular metabolism signalling. It is widely accepted that structure, composition differ across cell types. However, little about mitochondrial variability within the same type. To truly understand dynamics, we need to study individual types, as well on a single-cell level. Based our mitoXplorer 2.0 web tool, introduce 3.0 with new features adapted analysing sequencing data, focusing only mitochondria. We provide formatting script, scXplorer generate compatible files upload. This script creates pseudo-bulk transcriptomes of types from scRNA-seq data differential expression analysis subsequent mitochondria-centric classical interfaces. also matrix containing mitochondria-associated genes (mito-genes), which can be analysed cell-to-cell novel, interactive interfaces created 3.0: these help identify sub-clusters based mito-genes offer in-depth subpopulations. demonstrate usability predictive power using transcriptome Spinocerebellar Ataxia Type 1. identified several mito-processes majorly affected SCA1 Purkinje cells might contribute understanding decline loss this disease. MitoXplorer freely available at https://mitoxplorer3.ibdm.univ-amu.fr .

Language: Английский

Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Dec. 31, 2024

Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize discoveries, we provide comprehensive critical overview architecture concepts, Mendelian inheritance the latest insights omnigenic We explore roles common rare variants, gene-gene gene-environment interactions, epigenetic influences shaping phenotypes. Additionally, emphasize importance layers including genomic, transcriptomic, proteomic, epigenetic, metabolomic elucidating molecular mechanisms underlying neurodegeneration. Special attention is given missing heritability contribution particularly context pleiotropy network pleiotropy. examine application single-cell omics technologies, transcriptome-wide association studies, epigenome-wide studies as key approaches for dissecting at tissue- cell-type levels. Our review introduces OmicPeak Disease Trajectory Model, conceptual framework progression, which integrates across biological time points. This highlights adopting genetics approach unravel diseases. Finally, this emerging holistic exploration intricate landscape aim foundation establishing more architectures diseases, enhancing diagnostic precision, predicting pathogenic mechanisms, refining therapeutic strategies conditions.

Language: Английский