Integrating Sequencing Technologies in Personal Genomics: Optimal Low Cost Reconstruction of Structural Variants
Figure 2
Schematic of the reconstruction of a novel insertion and rearrangement analysis.
The horizontal positions of the reads indicate the mapping locations, and the colors refer to sequences from different genomic regions. (A–C) An example of the reconstruction of a novel insertion. (A) The region A (L bases) has multiple copies in the reference genome, and the region B has multiple copies in the target genome. The novel sequence is inserted right after a copy of region A and contains a copy of region B. (B) Split-reads such as read 1 or 2 will be needed to detect the left boundary of the insertion: read 1 is a single read that covers that boundary with M bases on the left (M>L); read 2 is a paired-end read with one end covering that boundary, and the two ends of read 2 can unambiguously map it back to the reference, thus revealing the insertion boundary; spanning-reads 3–7 are the reads from the novel insertion region; misleading-reads 8–9 are the reads from elsewhere in the target genome containing the same sequence contents of region B. Such reads may mislead the de novo assembly process for the novel insertion. (C) A possible set of resulting contigs after the reconstruction process. The gap is due to the false extension of the first contig caused by the misleading read 8. (D) An example of rearrangement analysis. The target individual genome has a deletion of region B from the reference. Although the sequence reads can detect such a variant, they may not be sufficient to determine whether this is a large deletion or translocation when the sequencing coverage is relatively low. The copy numbers of the genomic regions inferred from CGH array data can be integrated in the rearrangement analysis providing additional evidence of the SV types. For example, the 0 copy number of B inferred from CGH data #1 would be sufficient for us to confidently identify the deletion of B, while CGH data #2 indicates the translocation of B.