How to merge CNVs of 400 samples?

Question

[oghzzang]

Dear everyone,

I had detected CNVs from individual by CNVnator.

So, I have segments and their corresponding normalized RD scores by samples as below.

$cat S1.cnvnator.out

Sample CNV_type coordinates CNV_size normalized_RD

S1 duplication chr1:910101-914800 4700 1.67007

S1 deletion chr1:1288501-1290000 1500 0.127995

S1 deletion chr1:1366701-1367700 1000 0.0266648

S1 deletion chr1:2121701-2124400 2700 0.0418252

S1 deletion chr1:2227301-2229100 1800 0.262821

In several papers, they combined the calls with >80% reciprocally overlapped regions from each individual.

Q1. What is general definition of "reciprocally overlapped region"?

• When all samples share more than 80% reciprocally overlapped region? or
• When two or more samples (any threshold) share more than 80% reciprocally overlapped region?

Q2. How can I merge CNVs from all patients?

Many thanks.

Answer 1

[Pierre Lindenbaum]

I wrote this a few years ago but I haven't used / tested it much: http://lindenb.github.io/jvarkit/MergeCnvNator.html

[oghzzang]

Dear Pierre Lindenbaum,

Thank you for your reply.

I executed MergeCNVnator using my samples.

(java -jar ../dist/mergecnvnator.jar -r 0.5 -R /Reference/Homo_sapiens_assembly38.fasta in.list > out.r0.5.vcf)

When I use this tool, it seems to merge based on the first sample.

[S1.out]

deletion chr1:2-6000 5999 0 1.59373e-11 0 1.99216e-11 0 -1

deletion chr1:10501-10900 400 0.11168 2135.63 2.73059e-05 1 1 0.655738

[S2.out]

deletion chr1:3-6002 6000 0 1.59373e-11 0 1.99216e-11 0 -1

duplication chr1:11201-15700 4500 1.79337 1.41664e-09 3.90419e+06 0.0045581 7.33723e+07 0.637473

[S3.out]

deletion chr1:3-5888 6000 0 1.59373e-11 0 1.99216e-11 0 -1

duplication chr1:11101-17900 6800 1.5379 4.57429e-05 2.81502e+09 0.220526 2.83137e+09 0.524762

[Results] out.r0.5.vcf

CHROM POS ID REF ALT QUAL FILTER INFO FORMAT S1 S2 S3

chr1 2 . N DEL . . END=6000;IMPRECISE;SAMPLES=S1,S2,S3;SVLEN=5999;SVTYPE=DEL GT:CN:OV:P1:P2:P3:P4:Q0:RD 1/1:0:2:1.594e-11:0.00:1.992e-11:0.00:-1.000e+00:0.00 1/1:0:2:1.594e-11:0.00:1.992e-11:0.00:-1.000e+00:0.00 1/1:0:2:1.594e-11:0.00:1.992e-11:0.00:-1.000e+00:0.00

chr1 10501 . N DEL . . END=10900;IMPRECISE;SAMPLES=2016000051;SVLEN=400;SVTYPE=DEL GT:CN:OV:P1:P2:P3:P4:Q0:RD 1/1:0:0:2135.63:2.731e-05:1.00:1.00:0.656:0.112 ./. ./.

Many Thanks.