Limits...
Mitochondrial network genes in the skeletal muscle of amyotrophic lateral sclerosis patients.

Bernardini C, Censi F, Lattanzi W, Barba M, Calcagnini G, Giuliani A, Tasca G, Sabatelli M, Ricci E, Michetti F - PLoS ONE (2013)

Bottom Line: The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls.The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals.In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy and Cell Biology, School of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy. camilla.bernardini@rm.unicatt.it

ABSTRACT
Recent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal muscle, using microarray technology and gene regulatory network analysis. The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls. The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals. In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism. Overall, the analytical approach used in this study offer the possibility to observe higher levels of correlation (i.e. common expression trends) among genes, whose function seems to be aberrantly activated during the progression of muscle atrophy.

Show MeSH

Related in: MedlinePlus

Volcano plot.This representation of data resulting from microarray analysis compares the size of the fold change with the statistical significance level. x-axis: log2 of FC (fold change of differential gene expression between the ALS patients and controls); y-axis: corresponding p-value resulting from t-test used to measure the significance of the difference between samples in groups.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585165&req=5

pone-0057739-g003: Volcano plot.This representation of data resulting from microarray analysis compares the size of the fold change with the statistical significance level. x-axis: log2 of FC (fold change of differential gene expression between the ALS patients and controls); y-axis: corresponding p-value resulting from t-test used to measure the significance of the difference between samples in groups.

Mentions: To identify differentially expressed genes, the dataset was filtered by IQR, which allowed obtaining 2478 transcript clusters out of 8793. Thereafter, an absolute log2-fold change ≥1 and a BH-corrected P-value ≤0.05 were used as cutoffs (figure 3). This allowed identifying 96 differentially expressed transcripts (table 1), including 16 downregulated and 80 upregulated genes in the ALS patient samples compared to controls.


Mitochondrial network genes in the skeletal muscle of amyotrophic lateral sclerosis patients.

Bernardini C, Censi F, Lattanzi W, Barba M, Calcagnini G, Giuliani A, Tasca G, Sabatelli M, Ricci E, Michetti F - PLoS ONE (2013)

Volcano plot.This representation of data resulting from microarray analysis compares the size of the fold change with the statistical significance level. x-axis: log2 of FC (fold change of differential gene expression between the ALS patients and controls); y-axis: corresponding p-value resulting from t-test used to measure the significance of the difference between samples in groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585165&req=5

pone-0057739-g003: Volcano plot.This representation of data resulting from microarray analysis compares the size of the fold change with the statistical significance level. x-axis: log2 of FC (fold change of differential gene expression between the ALS patients and controls); y-axis: corresponding p-value resulting from t-test used to measure the significance of the difference between samples in groups.
Mentions: To identify differentially expressed genes, the dataset was filtered by IQR, which allowed obtaining 2478 transcript clusters out of 8793. Thereafter, an absolute log2-fold change ≥1 and a BH-corrected P-value ≤0.05 were used as cutoffs (figure 3). This allowed identifying 96 differentially expressed transcripts (table 1), including 16 downregulated and 80 upregulated genes in the ALS patient samples compared to controls.

Bottom Line: The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls.The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals.In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy and Cell Biology, School of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy. camilla.bernardini@rm.unicatt.it

ABSTRACT
Recent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal muscle, using microarray technology and gene regulatory network analysis. The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls. The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals. In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism. Overall, the analytical approach used in this study offer the possibility to observe higher levels of correlation (i.e. common expression trends) among genes, whose function seems to be aberrantly activated during the progression of muscle atrophy.

Show MeSH
Related in: MedlinePlus