Fig 1: DeepCLIP predicts increased TDP-43 binding as mechanism behind ACADM exon 6 skipping. (A) DeepCLIP TDP-43 profile across the 5'ss of ACADM exon 6 with wt indicated in black and patient mutation indicated in red. Along the first axis the sequence is shown and along the second axis the DeepCLIP BLSTM values are shown. SPRi oligo location and SSO locations are indicated in blue and red bars above and below the sequence, respectively. (B) Splicing of wt and mutant minigenes with either TDP-43 targeting siRNA or non-targeting siRNA determined by RT-PCR. (C) Western blot of TDP-43 and HPRT from siRNA and minigene transfected samples. (D) Splicing of wt and mutant minigenes treated with either a control SSO (Ctrl-SSO), SSO1, or SSO2 determined by RT-PCR. (E) DeepCLIP profile of short RNA oligos used in SPRi measurement, reference in black and +7A>G variant in red. (F) The difference in DeepCLIP binding profiles in (E) between reference and variant. Positive score indicates higher score in variant. (G) SPRi measurements of TDP-43 binding to the wt oligo in (E). (H) SPRi measurements of TDP-43 binding to the variant oligo in (E). In both (G) and (H), the black line indicates the fitted binding model.