Fig 1.
Gene level network analysis of transcriptome changes in motor neurons from C9ORF72-ALS cases.
WGCNA analysis identified six gene networks which were dysregulated between C9ORF72-ALS and control samples. A clustering tree and heat map are shown illustrating separation of the gene networks, a lower branch height or darker colour denotes a greater Pearson correlation coefficient between pairs of genes.
Table 1.
Gene level network analysis of transcriptome changes in motor neurons from C9ORF72-ALS cases.
Fig 2.
Gene level network analysis of transcriptome changes in lymphoblastoid cell lines derived from C9ORF72-ALS cases.
WGCNA analysis identified nine gene networks which were dysregulated between C9ORF72-ALS and control samples. A clustering tree and heat map are shown illustrating separation of the gene networks, a lower branch height or darker colour denotes a greater Pearson correlation coefficient between pairs of genes. The median fold change of genes within each network and the functional enrichment of each of the gene networks is tabulated (B). A fold change of >1 equates to up-regulation and a fold change of <1 equates to down-regulation.
Table 2.
Gene level network analysis of transcriptome changes in lymphoblastoid cell lines derived from C9ORF72-ALS cases.
Fig 3.
Frequency of exon inclusion and exclusion events.
Plots of median and 95% CI for numbers of (A) exon inclusion and (B) exon exclusion events in C9ORF72-ALS (+), non-C9ORF72 ALS (-) and control (C) derived lymphoblastoid cell lines, as determined by FIRMA score. There was no significant difference between sample groups.
Fig 4.
Plots of θ against the mean splicing rate with 95% confidence intervals.
Exon inclusion events are shown in the left panel and exclusion inclusion events are shown in the right panel. θ is higher indicating reduced consistency of splicing in (A) C9ORF72-ALS (+) compared to non-C9ORF72 ALS (-) and control (C) derived lymphoblastoid cell lines; and (B) in cell lines derived from patients with rapid (length <2 years, Fast) compared to slowly (length >4 years, Slow) progressive C9ORF72-ALS.
Fig 5.
RNA foci in lymphoblastoid cell lines derived from patients with short or long survival.
RNA FISH was performed for sense and antisense RNA foci in lymphoblastoid cells. Example cells are shown derived from patients with rapid (length <2 years, Fast, upper panels) compared to slowly (length >4 years, Slow, lower panels) progressive C9ORF72-ALS. GGGGCC-repeat sense RNA foci are visualised (arrowheads) in the left panels whereas GGCCCC-repeat antisense RNA foci are visualised (arrowheads) in the right panels. Scale bar 10 µm.
Table 3.
Clinical information relating to motor neurons laser captured from ALS patients and controls, utilised in gene level microarray analysis.
Table 4.
Clinical information relating to lymphoblastoid cell lines derived from ALS patients and controls, utilised in exon level microarray analysis.