Fig. 6: ALS iPSMNs and post-mortem tissue accumulate somatic mutations and gene fusions.

a Violin plots showing the partial residuals of somatic mutations, controlling for age and read depth, identified in Answer ALS iPSMNs in ALS (red, n = 238) and CTRL (blue, n = 42) samples, for all mutation types, insertions, deletions, and single-nucleotide variants (SNV). Statistics are from the generalised linear model Wald test using a Poisson distribution. b Forest plot showing the generalised linear model point estimate and 95% confidence interval of changes in mutation types (SNV, blue; insertion, red; deletion, green) in ALS genetic subgroups versus controls. The vertical dashed line indicates no difference, to the right of the dashed line indicates an increase in ALS. c, d As for (a, b) except in NYGC post-mortem spinal cord samples (n = 214 ALS, n = 57 controls). In addition to age and read depth, the sequencing instrument is also controlled for. e Violin plots showing the partial residuals of gene fusions in CTRL (blue, n = 90) and ALS (red, n = 306) in paired-end sequenced iPSMNs, controlling for age, read depth and dataset. Statistics are from the generalised linear model Wald test using a Poisson distribution. f Forest plot showing the generalised linear model point estimate and 95% confidence interval changes in each genetic subtype versus controls. g, h As for (e, f) except in post-mortem (n = 214 ALS, n = 57 controls), controlling for age, read depth, dataset and sequencing instrument. In the boxplots, whiskers (error bars) represent 1.5 times the interquartile range, the hinges correspond to the first and third quartiles, and the centre represents the median. **** represents P < 0.0001, ^*** P < 0.001, ^**P < 0.01, ^*P < 0.05.