Dataset Information

Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

ABSTRACT: This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period.Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n?=?4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks.Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection.Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression across time correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid.

SUBMITTER: Mukund K

PROVIDER: S-EPMC4136975 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

Mukund Kavitha K Mathewson Margie M Minamoto Viviane V Ward Samuel R SR Subramaniam Shankar S Lieber Richard L RL

Muscle & nerve 20140317 5

<h4>Introduction</h4>This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period.<h4>Methods</h4>Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n = 4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks.<h4>Results</h4>Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoform ...[more]

PMID: 24536034

Similar Datasets

Project description:IntroductionWe previously developed a tandem mass spectrometry-based label-free targeted metabolomics analysis framework coupled to two distinct chromatographic methods, reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), with dynamic multiple reaction monitoring (dMRM) for simultaneous detection of over 200 metabolites to study core metabolic pathways.ObjectivesWe aim to analyze a large-scale heterogeneous data compendium generated from our LC-MS/MS platform with both RPLC and HILIC methods to systematically assess measurement quality in biological replicate groups and to investigate metabolite abundance changes and patterns across different biological conditions.MethodsOur metabolomics framework was applied in a wide range of experimental systems including cancer cell lines, tumors, extracellular media, primary cells, immune cells, organoids, organs (e.g. pancreata), tissues, and sera from human and mice. We also developed computational and statistical analysis pipelines, which include hierarchical clustering, replicate-group CV analysis, correlation analysis, and case-control paired analysis.ResultsWe generated a compendium of 42 heterogeneous deidentified datasets with 635 samples using both RPLC and HILIC methods. There exist metabolite signatures that correspond to various phenotypes of the heterogeneous datasets, involved in several metabolic pathways. The RPLC method shows overall better reproducibility than the HILIC method for most metabolites including polar amino acids. Correlation analysis reveals high confidence metabolites irrespective of experimental systems such as methionine, phenylalanine, and taurine. We also identify homocystine, reduced glutathione, and phosphoenolpyruvic acid as highly dynamic metabolites across all case-control paired samples.ConclusionsOur study is expected to serve as a resource and a reference point for a systematic analysis of label-free LC-MS/MS targeted metabolomics data in both RPLC and HILIC methods with dMRM.

Dataset Information

Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

Publications

Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets