Annotate fusion genes

[alumi]

This PR adds a new namespace varity.fusion to annotate fusion genes for breakpoints.

varity.fusion assumes a variant in the format of VCF as an input.
varity.fusion/variant->breakpoints converts a variant into an breakpoint entry.

varity/src/varity/fusion.clj

Lines 229 to 231 in 12c1026

	(defn variant->breakpoints
	"Converts each allele in a VCF-style variant into a map used in
	`varity.fusion`. Returns a lazy sequence of the same length with alleles."

Then, varity.fusion/fusion-transcripts annotates fusion transcripts for the breakpoint.
This is a function intended for ease of use and is just a simple combination of the following 3 functions.

varity/src/varity/fusion.clj

Lines 194 to 196 in 12c1026

	(defn fusion-transcripts
	"Like `fusion-genes` but returns only in-frame and actually fused genes. An
	amino acid sequence is added as `:transcript` for each candidates."

1. varity.fusion/fusion-genes searches for all possible gene pairs from refGene and determines if each pair can form a valid fusion transcript.
   

   varity/src/varity/fusion.clj

   Lines 151 to 160 in 12c1026

   	(defn fusion-genes
   	"Returns a lazy sequence of annotations of all possible combinations of fusion
   	genes. An annotation is a map containing the following key-values:
   	- `:breakpoints` Given breakpoints in the order of 5'-part, 3'-part.
   	- `:genes` Candidate genes for each of the `:breakpoints`.
   	- `:fusion?` `true` iff the genes form a fused transcript.
   	- `:breakpoint-regions` Genic regions for each of the `:breakpoints`.
   	- `:transcript-regions` A sequence of regions corresponding to each exon of a
   	resulting transcript. May not be fused or may be `nil` if no transcription is
   	expected."

2. varity.fusion/in-frame? checks if a fused sequence is aligned in or out of reading frame.
   

   varity/src/varity/fusion.clj

   Line 175 in 12c1026

   (defn in-frame?

3. varity.fusion/transcript gives an amino acid sequence for a fusion gene.
   

   varity/src/varity/fusion.clj

   Line 186 in 12c1026

   (defn transcript

---

The annotation algorithm is originally developed at Cancer Precision Medicine Center, Japanese Foundation for Cancer Research and I re-implemented it with some additional features such as:

• support for inserted sequences
• specialized handling of UTRs
• wider support of VCF notations

Thankfully, @athos, @r6eve and @k-kom have already reviewed this PR internally.

[codecov]

Codecov Report

Merging #52 (9a0dfdb) into master (f84c720) will increase coverage by 1.75%.
The diff coverage is 65.77%.

@@            Coverage Diff             @@
##           master      #52      +/-   ##
==========================================
+ Coverage   43.49%   45.24%   +1.75%     
==========================================
  Files          15       16       +1     
  Lines        1805     1954     +149     
  Branches       39       61      +22     
==========================================
+ Hits          785      884      +99     
- Misses        981     1009      +28     
- Partials       39       61      +22     

Impacted Files	Coverage Δ
src/varity/fusion.clj	65.77% <65.77%> (ø)
src/varity/ref_gene.clj	80.75% <0.00%> (+0.29%)	⬆️

---

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[totakke]

Thank you for the great feature. The implementation looks good to me. I have left a few trivial comments.

[totakke]

Please add 1.11 to also .github/workflows/build.yml.

varity/.github/workflows/build.yml

Line 11 in f84c720

clojure: ['1.8', '1.9', '1.10']

[totakke]

Prural Acknowledgements generally.

[alumi]

@totakke Thank you for your review! 🙏 I fixed the problems you pointed out by bf7445b and 9a0dfdb.

[totakke]

Speedy. Thank you.