Missing all IGH fusions

[ndaniel]

It looks like all IGH fusions are missed. IGH fusions are for example found in lymphoblastic leukemias.

For example, the IGH-DUX4 fusion is missed in NALM-6 cell line (using this RNA-seq data from CCLE https://gdc-portal.nci.nih.gov/legacy-archive/files/6fa77b04-bb16-49c5-8033-79dd76860c97 ).

[friend1ws]

Thank you very much for the interest in our software.
Yes, IGH-DUX4 fusion is one of few example which our approach miss.
Our approach accepts list of of chimeric reads generated by aligner (e.g., *.Chimeric.out.sam by STAR), and filter them to identify highly reliable fusions (so mostly similar to the approach by STAR-fusion).
Therefore, actually, there are no chimeric reads supporting IGH-DUX4 fusions at the stage of *.Chimeric.out.sam. (when using STAR), and IGH-DUX4 cannot be found by our software.

I guess either IGH or DUX4 is highly repetitive sequence and STAR miss to accurately align short reads covering these genes...

I'm considering resolve this issue by other approaches.

[ndaniel]

IGH-DUX4 fusion is one of few example which our approach miss.

Our there are more than 40 known IGH fusions (see: http://atlasgeneticsoncology.org/Genes/GC_IGH.html ) so therefore a lot of fusion genes that are missed! Also I would guess that also fusion CIC-DUX4 is missed too (see: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099439 )

STAR and STAR-fusion are known to miss almost all IGH fusions. Out there are fusion callers that are very well known to be able to find IGH fusions in RNA-seq data, like for example CICERO and FusionCatcher.

I guess either IGH or DUX4 is highly repetitive sequence and STAR miss to accurately align short reads covering these genes...

I guess that the IGH-DUX4 fusion is missed because all of these three reasons together:

• IGH annotation that is used is not optimal because there is high variation at IGH@ from one individual to another (i.e. the standard GTF file is not good enough for finding IGH fusion genes);
• DUX4 has a very large number of pseudogenes which have very high sequence similarity;
• IGH fusions in general may have a random sequence of 5bp to 40bp inserted at fusion junction (e.g. STAR and STAR-fusion cannot handle this kind of alignment).

Here is a small FASTQ files test for fusions which contains 17 known fusions and it can be used to asses quickly what fusions are missed by a fusion caller:
https://sourceforge.net/projects/fusioncatcher/files/test/