R/detect_arm_overfragmentation.R
detect_arm_overfragmentation.RdThe fragmentation of a chromosome arm is assessed with a statistical test based on counting the size of the copy number segments mapping to the arm. This analysis works only at the level of clonal CNAs.
CNAqc counts, for every arm with lenght $L$ nucleotides:
- the number of mapped CNA segments shorter than a percentage of $L$; - the number of mapped CNA segments longer than a percentage of $L$.
A one-sided Binomial test is used to compute a p-value. In this way the test accounts for the difference in lenghts of the chromsome arms; a p-value per arm is reported and adjusted for multiple hyoptheses (Bonferroni).
detect_arm_overfragmentation(
x,
alpha = 0.01,
genome_percentage_cutoff = 0.2,
minimum_segments_for_testing = 10
)A CNAqc object.
Confidence level for the tests, for instance 0.05.
Segments are considered long or short depending on whether
they are longer (in basepairs) than genome_percentage_cutoff * L bases, where L
is the arm length for the reference genome. Default is 0.2 (twenty percent).
Smallest number of segments required to actually test
a certain arm Default is 10 segments. This number influences the correction for mulitple
hypothesis testing.
A CNAqc objectwith the results.
data('example_dataset_CNAqc')
x = init(mutations = example_dataset_CNAqc$mutations, cna = example_dataset_CNAqc$cna, purity = example_dataset_CNAqc$purity)
#>
#> ── CNAqc - CNA Quality Check ───────────────────────────────────────────────────
#>
#> ℹ Using reference genome coordinates for: GRCh38.
#> ✔ Found annotated driver mutations: TTN, CTCF, and TP53.
#> ✔ Fortified calls for 12963 somatic mutations: 12963 SNVs (100%) and 0 indels.
#> ! CNAs have no CCF, assuming clonal CNAs (CCF = 1).
#> ✔ Fortified CNAs for 267 segments: 267 clonal and 0 subclonal.
#> ✔ 12963 mutations mapped to clonal CNAs.
x = detect_arm_overfragmentation(x)
#> ℹ One-tailed Binomial test: 8 tests, alpha 0.01. Short segments: 0.2% of the reference arm.
#> ✔ chr7p, p = 1.71798691840001e-24 ~ 34 segments, 34 short.
#> ✔ chr1p, p = 1.62738995200002e-15 ~ 24 segments, 23 short.
#> ✔ chr11q, p = 2.4788992e-07 ~ 14 segments, 12 short.
#> ✔ chr1q, p = 4.34176000000001e-08 ~ 13 segments, 12 short.
#> ✔ chr12q, p = 4.34176000000001e-08 ~ 13 segments, 12 short.
#> ✔ chr3q, p = 4.52608e-06 ~ 12 segments, 10 short.
#> ✔ chr7q, p = 4.52608e-06 ~ 12 segments, 10 short.
#> ✔ chr8p, p = 9.21599999999998e-07 ~ 11 segments, 10 short.
#> ℹ 8 significantly overfragmented chromosome arms (alpha level 0.01).
# Report to console
print(x)
#> ── [ CNAqc ] MySample 12963 mutations in 267 segments (267 clonal, 0 subclonal).
#>
#> ── Clonal CNAs
#>
#> 2:2 [n = 7478, L = 1483 Mb] ■■■■■■■■■■■■■■■■■■■■■■■■■■■ { CTCF }
#> 4:2 [n = 1893, L = 331 Mb] ■■■■■■■
#> 3:2 [n = 1625, L = 357 Mb] ■■■■■■
#> 2:1 [n = 1563, L = 420 Mb] ■■■■■■ { TTN }
#> 3:0 [n = 312, L = 137 Mb] ■
#> 2:0 [n = 81, L = 39 Mb] { TP53 }
#> 16:2 [n = 4, L = 0 Mb]
#> 25:2 [n = 2, L = 1 Mb]
#> 3:1 [n = 2, L = 1 Mb]
#> 106:1 [n = 1, L = 0 Mb]
#>
#> ℹ Sample Purity: 89% ~ Ploidy: 4.
#>
#> ℹ There are 3 annotated driver(s) mapped to clonal CNAs.
#> chr from to ref alt DP NV VAF driver_label is_driver
#> chr2 179431633 179431634 C T 117 77 0.6581197 TTN TRUE
#> chr16 67646006 67646007 C T 120 54 0.4500000 CTCF TRUE
#> chr17 7577106 7577107 G C 84 78 0.9285714 TP53 TRUE
#> ✔ Arm-level fragmentation analysis: 8 segments overfragmented.