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Developed in the Data Sciences Platform at the Broad Institute, the toolkit offers a wide variety of tools with a primary focus on variant discovery and genotyping. Its powerful processing engine and high-performance computing features make it capable of taking on projects of any size. Learn more

(How to part II) Sensitively detect copy ratio alterations and allelic segments Follow

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    Bilyana Stoilova

    Hi,
    First of all, thank you for putting these two tutorials together - this is the best WES CNV pipeline I have used. Could I just check with you a few settings? When using CallCopyRatioSegments the default parameters are --neutral-segment-copy-ratio-lower-bound 0.9 and --neutral-segment-copy-ratio-upper-bound 1.1, which corresponds to heterozygous copy number gain or loss in 20% of cells. This seems quite high number and I am wondering whether my data will allow me to call, for example heterozygous copy number gain or loss in 5% of cells by changing the parameters to --neutral-segment-copy-ratio-lower-bound 0.975 --neutral-segment-copy-ratio-upper-bound 1.025? In order to do so, I need to understand what my background it and make sure my calls are not just noise. Do you have a suggestion how I can define the background level and set a sample-specific threshold to confidently call CNV gains and losses with lower frequencies?
    Furthermore, the outputs from ModelSegments has a column called NUM_POINTS_COPY_RATIO - what does this parameter mean? I noticed that for some segments with very high or vary low copy ratio values, this number is very low. For example here for a sample with monosomy 7, e.g. line 4 and 9 in bold, NUM_POINTS_COPY_RATIO is 1:

    CONTIG START END NUM_POINTS_COPY_RATIO MEAN_LOG2_COPY_RATIO
    chr7 31127 2610604 371 -0.970608
    chr7 2631917 6764353 545 -0.968955
    chr7 6765438 6766161 1 -29.219897
    chr7 6805656 38260513 1695 -0.975855
    chr7 38261822 38358772 15 0.38893
    chr7 38358773 38385336 6 -0.918812
    chr7 38389472 73111427 1497 -0.979949
    chr7 73184300 73184960 1 -29.526709
    chr7 73192104 77027191 584 -1.027995
    chr7 77027848 77056891 4 -15.357203
    chr7 77058881 77736804 89 -1.367833
    chr7 77749237 139065288 4597 -0.987914
    chr7 139073532 139080077 5 -1.073054
    chr7 139080078 142346386 490 -0.95668
    chr7 142618867 142797361 27 0.165386
    chr7 142797362 144187184 232 -0.957674
    chr7 144258427 144276715 6 -2.782032
    chr7 144282040 144318694 7 -0.972986
    chr7 144362468 144372526 6 -11.344774
    chr7 144372527 144375110 3 -3.65833
    chr7 144376855 150860905 407 -0.97085
    chr7 150860906 159144997 729 -0.968317

    Do I need to exclude these lines  with low NUM_POINTS_COPY_RATIO values from the analysis? I see you have them in the tutorial too but haven't discussed what they mean. Thank you, Bilyana

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