Analysis of insertions in MMTV-induced mammary tumors by shear-splink and RE-splink. (A) Venn diagram showing strong overlap between MMTV insertions at known CISs for the shear-splink and RE-splink methods. The overlapping CISs are strongly enriched for components of the Wnt and Fgf signaling pathways, which are known to cooperate during mammary tumorigenesis. (B) Total number of unique insertions (>0 and >1 sequence coverage and unique LPs) identified in a panel of 16 MMTV-induced tumors using shear-splink or RE-splink with BfaI or NlaIII. A high level of variability is observed in the absolute number of insertions not linked to a CIS, in contrast to a comparable number of insertions mapping to known CISs. (C) Bar diagrams showing percentages of insertions representing known CISs for shear-splink and for RE-splink with BfaI and NlaIII. Increasing the threshold to higher sequence coverage of unique LPs increases the fraction of insertions representing known CISs. For all thresholds tested (>0, >1, >2, >5, >10), the percentage of insertions mapping to known CISs is higher for shear-splink than for RE-splink. (D) Receiver Operating Characteristic (ROC) curves for the RE-splink and shear-splink methods show for shear-splink that enrichment in the identification of relevant insertions does not result in reduced sensitivity. The ROC curves are built upon unique LPs for the shear-splink analysis and sequence coverage for the RE-splink experiments. By moving along the ROC curves from left to right, the ratios between true positives (sensitivity) and false positives (specificity) are visualized.
