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Graph handling issue with AltSplice Insertion & indel that shifts back to original reading frame #726

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zhuchcn opened this issue Apr 27, 2023 · 0 comments · Fixed by #725

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zhuchcn commented Apr 27, 2023

This is when a AltSplice insertion (frameshift +2) with an intronic indel (frameshift +1). The intronic indel brings it back to the original reading frame.

Original TVG looks like this:

                                                                        
                G-----------------|-------------------------------------|-------------------------------
               /                  |                                    /                                \
              |   GTCTC..TTTTT-TT-AG-----------------------------------                                  |
              |  /            \                                                                          |
              | |              T-                                                                        |
              | |                \                                                                       |
              | |                 |                                                                      |
              | |              GGTCTCTATGAATAAAGAAAAGCAAATAGAATCTTATCAG                                  |            T
              | |             /   |                                    \                                 |           / \
0- GTCGG..TTTGT-G-AGTGG..GGCAA-G----------------------------------------GTACCAGCATCAAGATGATTTATGGTAATAAG-ATATA..AACTG-C-TTAGG..CTTGA
                                  |                                     |
                G-------------------------------------------------------|-------------------------------
               /                  |                                    /                                \
              |   GTCTC..TTTTT-TT-AG-----------------------------------                                  |
              |  /            \                                                                          |
              | |              T-                                                                        |
              | |                \                                                                       |
              | |                 |                                                                      |
              | |              GGTCTCTATGAATAAAGAAAAGCAAATAGAATCTTATCAG                                  |            T
              | |             /   |                                    \                                 |           / \
1-  TCGG..TTTGT-G-AGTGG..GGCAA-G----------------------------------------GTACCAGCATCAAGATGATTTATGGTAATAAG-ATATA..AACTG-C-TTAGG..CTTGA
                                  |                                     |
                G-------------------------------------------------------|-------------------------------
               /                  |                                    /                                \
              |   GTCTC..TTTTT-TT-AG-----------------------------------                                  |
              |  /            \                                                                          |
              | |              T-                                                                        |
              | |                \                                                                       |
              | |                 |                                                                      |
              | |              GGTCTCTATGAATAAAGAAAAGCAAATAGAATCTTATCAG                                  |            T
              | |             /   |                                    \                                 |           / \
1-   CGG..TTTGT-G-AGTGG..GGCAA-G----------------------------------------GTACCAGCATCAAGATGATTTATGGTAATAAG-ATATA..AACTG-C-TTAGG..CTTGA
                                  |

Issue happens in the middle of doing variant alignment. Below is a local piece of the graph, on reading frame 0. The red rectangle TAG is merged from the intronic deletion (TT->T) and its downstream AG, from the inserted sequence of the AltSplice event from reading frame 1. This merging happens when alignment variants at reading frame 1. So now when we align the nodes that starts from node GTCTC..TTTTT, we should treat TAG as a frameshifting, but it maybe failed to be recognized because it's inframe.

image

zhuchcn added a commit that referenced this issue Apr 27, 2023
… indel that goes back to the original reading frame. #726
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