Extended Data Fig. 10: Application of the NeoLoopFinder framework to developmental diseases with genomic rearrangements.

a, CHi-C map reconstruction and neo-loop detection for an inversion event (inv1) in the mouse forelimb at embryonic day 11.5 (E11.5). Data were downloaded from Kragesteen BK et al. Nature Genetics 2018. (left) CHi-C map of the wild-type forelimb. The Pitx1 gene shows weak interactions with the Pen enhancer. Blue circles indicate the predicted chromatin loops by Peakachu. (middle) Original CHi-C map of the forelimb that contains a homozygous inversion of a 113-kb fragment containing Pen. (right) Reconstructed CHi-C map for the inversion. Note the neo-loop between Pitx1 and the Pen enhancer was correctly detected by NeoLoopFinder. b, CHi-C map reconstruction and neo-loop detection for a duplication event (Dup-C) in the mouse limb buds at E12.5. Data were downloaded from Franke M et al. Nature 2016. The duplicated region (blue and green arrows) contains both the Sox9 enhancers (marked by H3K27ac peaks) and the Kcnj2 gene. The rightmost panel shows the reconstructed chromatin interaction map near the duplication breakpoints. Yellow circles highlight the Kcnj2-involved neo-loops. There are also two more predicted neo-loops in this region (blue circles). c, CHi-C map reconstruction and neo-loop detection for an inversion event (InvC) in E12.5 limb buds. Data were downloaded from Despang A et al. Nature Genetics 2019. The inverted region (green bar in the middle panel) contains Sox9 enhancers (marked by H3K27ac peaks) and the TAD boundary separating the Sox9 enhancers and the Kcnj2 gene. The rightmost panel shows the reconstructed map for the whole region. The blue circles indicate the detected neo-loops, and yellow circles highlight the Kcnj2-involved neo-loops.