Multi-allelic CNV (Beginner's level question)

Question

[jimkozubek]

I am looking at some CNV information, which I did not run, but obtained from the MSSNG database. And after reading the documentation, I still have a question.

The field CopyNumber sometimes lists values with just one number such as 0 or 3, but sometimes it looks biallelic, such as 3|4 or just 0|1 But wait, there’s more. Sometimes the value for a CopyNumber is: 3|5|4|7

How do you interpret this?

Answer 1

[Kevin Blighe]

It is likely related to the fact that the copy number variant information for MSSNG was derived from 2 sources:

1. Illumina platforms
2. Complete Genomics

The Illumina data was processed with ERDS and CNVnator - these are likely the single digit copy number values that you see. They are whole integers because a Hidden Markov Model was used.

The Complete Genomics data is haplotype-resolved, so, the 3|4, etc, likely relates to copy number 3 on one allele, and 4 on the other.

I cannot comment on the other ones, such as 3|5|4|7

For a full clarification, I would encourage you to contact the team directly - email found here: https://research.mss.ng/

Kevin

[jimkozubek]

Thank you. The HMM insight sounds correct.

I am not sure these split values are due to various sequencing platforms, because in this case each line is a specific sample, and only one sequencing platform is identified per sample, such as each line says CG or HiSeqX, and only one per line.

So, 3|4 value is for only one line with one sequencing platform. The same is true for 3|5|4|7

I think it is possible that their are ALT contigs in v38 and it could be due to that.

I agree that MSSNG should be the best place to find out, since it is their nomenclature, and will post their response, if they do get back to me.

[jimkozubek]

Here is an example such that Copy Number is listed as 3|5|4|7 for only one sample and only one platform HISEQX. I have posed the question to MSSNG

Sample  Chromosome      Start   End     CNVType CopyNumber      Size    Overlap Putative_Inheritance    GC_Content_Percent   CytobandAnn      Gene_Symbol     Gene_egID       Exon_Symbol     Exon_egID       CDS_Symbol      CDS_egID        ISCA_region  CNV_ISCA_percOverlap     ExAC_pLI        UncleanGenome_percOverlap       MPO_NervousSystem       HPO_NervousSystem       CGD  OMIM_MorbidMap   DECIPHER_region CNV_decipher_percOverlap        DGV_N_studies   DGVpercFreq_subjects_allStudies DGVpercFreq_su
bjects_coverageStudies  DGV_percOverlap_any     DGV_50percRecipOverlap  CGparentalPercFreq_50percRecipOverlap   erdsPercFreq_5
0percRecipOverlap       cnvnatorPercFreq_50percRecipOverlap     Comment Curated Platform

SampleXYZ       21      9964001 11188000        DUP     3|5|4|7 1224000 0.838|1.000     no_parent       30.7    21p11.2|21p11.1       BAGE4|TPTE|BAGE2|BAGE|BAGE3|BAGE5       7179|85318|574  BAGE4|TPTE|BAGE2|BAGE|BAGE3|BAGE5       7179|85318|574  BAGE4|TPTE|BAGE2|BAGE|BAGE3|BAGE5     7179|85318|574          0               86.357                          7179:TPTE:|85318:BAGE3:|574:BAGE:             0       0       0       0       40.041  0       0       99.822  97.724  -               HISEQX