Extended Data Fig. 5. Differences in sample technical factors where UNC13A CE was detected and undetected vary between cortical and spinal tissues.

Targeted long reads in FTLD frontal cortex show that UNC13A CE and IR occur independently in-vivo. (a) Detection rate of UNC13A CE across tissues by RNA sequencing platform and read length. UNC13A CE was more likely to be detected in cervical spinal cord and motor cortex when sequenced on machines with 125 bp compared to 100 bp. (b) No significant differences in total RNA-seq library size (log10 scaled). (c) RNA integrity score (RIN) was significantly lower in motor and temporal cortices in samples where UNC13A was detected. (d) Cell type decomposition revealed that samples with UNC13A CE detected had a higher proportion of neurons in cervical and lumbar spinal cord, whereas in frontal, temporal, and motor cortex samples with UNC13A CE detected had a lower proportion of neurons, and in motor and temporal cortex samples with UNC13A CE detected had a higher proportion of astrocytes. Astrocy. - Astrocytes, Endothi. - Endothelial, Microgl. - Microglia. Neur. - Neurons, Oligiodendr. - Oligiodendrycytes. P-values shown are from Fisher’s exact test (a) or Wilcoxon test (b–d). N tissue samples show below in brackets. Box plots (a–d): boundaries 25-75th percentiles; midline, median; whiskers, Tukey style. (e) Percentage of targeted UNC13A long reads with TDP-43 regulated splice events that contain either both, CE, or IR in four in FTLD frontal cortices. (f) Percentage of all targeted UNC13A long reads in (a) containing neither CE nor IR, both, or either CE or IR.