Type: | Package |
Title: | Calculate Chromosomal Instability Metrics |
Version: | 0.1.0 |
Author: | Vishal H. Oza, Roshan Darji, Brittany N. Lasseigne |
Maintainer: | Vishal H. Oza <vishoza@uab.edu> |
Description: | Implement various chromosomal instability metrics. 'CINmetrics' (Chromosomal INstability metrics) provides functions to calculate various chromosomal instability metrics on masked Copy Number Variation(CNV) data at individual sample level. The chromosomal instability metrics have been implemented as described in the following studies: Baumbusch LO et al. 2013 <doi:10.1371/journal.pone.0054356>, Davidson JM et al. 2014 <doi:10.1371/journal.pone.0079079>, Chin SF et al. 2007 <doi:10.1186/gb-2007-8-10-r215>. |
License: | GPL-3 |
Encoding: | UTF-8 |
LazyData: | true |
RoxygenNote: | 7.1.1 |
Depends: | R (≥ 2.10), stats |
Suggests: | knitr, rmarkdown |
VignetteBuilder: | knitr |
NeedsCompilation: | no |
Packaged: | 2021-07-29 16:04:48 UTC; vishal |
Repository: | CRAN |
Date/Publication: | 2021-08-02 08:20:02 UTC |
CINmetrics
Description
Calculate all CINmetrics on a given dataframe
Usage
CINmetrics(
cnvData,
segmentMean_tai = 0.2,
segmentMean_cna = (log(1.7, 2) - 1),
segmentMean_base_segments = 0.2,
segmentMean_break_points = 0.2,
segmentMean_fga = 0.2,
numProbes = NA,
segmentDistance_cna = 0.2,
minSegSize_cna = 10,
genomeSize_fga = 2873203431
)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean_tai |
numerical value for the minimum segment_mean cutoff/ threshold for Total Aberration Index calculation. Default is 0.2 |
segmentMean_cna |
numerical value for the minimum segment_mean cutoff/ threshold for Copy Number Aberration calculation. Default is 0.2 |
segmentMean_base_segments |
numerical value for the minimum segment_mean cutoff/ threshold for Base segments calculation. Default is 0.2 |
segmentMean_break_points |
numerical value for the minimum segment_mean cutoff/ threshold for Break points calculation. Default is 0.2 |
segmentMean_fga |
numerical value for the minimum segment_mean cutoff/ threshold for Fraction of genome altered calculation. Default is 0.2 |
numProbes |
Number of Probes |
segmentDistance_cna |
Segment distance threshold |
minSegSize_cna |
Minimum segment size |
genomeSize_fga |
Size of the genome derived from Affymetrix 6.0 array probe. Default is 2873203431 calculated based on hg38 **excluding sex chromosomes** |
Value
All Chromosomal INstability metrics
Examples
CINmetrics(cnvData = maskCNV_BRCA)
Copy Number Aberration
Description
Calculates the number of copy number aberrations
Usage
cna(
cnvData,
segmentMean = (log(1.7, 2) - 1),
numProbes = NA,
segmentDistance = 0.2,
minSegSize = 10
)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean |
numerical value for the minimum segment_mean cutoff/ threshold. Default is 0.2 |
numProbes |
Number of Probes |
segmentDistance |
Segment distance threshold |
minSegSize |
Minimum segment size |
Details
Copy Number Aberrations (CNA) (Davidson JM, et al), are defined as a segment with copy number outside the pre-defined range of 1.7-2.3
(\log_2 1.7 -1) \le \bar{y}_{S_i} \le (\log_2 2.3 -1)
that is not contiguous with an adjacent independent CNA of identical copy number. For our purposes, we have adapted the range to be
|\bar{y}_{S_i}| \ge |\log_2 1.7|
, which is only slightly larger than the original.
It is nearly identical to countingBreakPoints, except this one calculates breaks as adjacent segments that have a difference in segment means of \ge 0.2
.
Total\ Copy\ Number\ Aberration = \sum^{R}_{i = 1} n_i \ where \
\bar{y}_{S_i}| \ge |\log_2{1.7}|, \
\bar{y}_{S_{i-1}} - \bar{y}_{S_i}| \ge 0.2, \
d_i \ge 10
Value
Number of copy number aberrations between segments
See Also
Examples
cna(cnvData = maskCNV_BRCA)
countingBaseSegments
Description
Function for counting altered base segments
Usage
countingBaseSegments(cnvData, segmentMean = 0.2, numProbes = NA)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean |
numerical value for the minimum segment_mean cutoff/ threshold. Default is 0.2 |
numProbes |
Number of Probes |
Details
The Altered Base Segment calculation takes all the CNV data for a single patient and first filters it for a segmentation mean of > 0.2 and, if specified, the minimum number of probes covering that area. Then, it calculates the sums of the lengths of each segment for a particular patient and outputs that.
Number\ of\ Altered\ Bases = \sum^{R}_{i = 1} d_i\ where\ |\bar{y}_{S_i}| \ge 0.2
Value
Number of Base segments for each unique sample
Examples
countingBaseSegments(cnvData = maskCNV_BRCA)
countingBreakPoints
Description
The Break Point calculation takes all the CNV data for a single patient and first filters it for segmentation mean of > 0.2 and, if specified, the minimum number of probes covering that area. Then it counts the number of rows of data and multiplies it by 2. This represents the break points at the 5' and 3' ends of each segment.
Number\ of \ Break\ Points = \sum^{R}_{i = 1} (n_i \cdot 2)\ where\ |\bar{y}_{S_i}| \ge 0.2
Usage
countingBreakPoints(cnvData, segmentMean = 0.2, numProbes = NA)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean |
numerical value for the minimum segment_mean cutoff/ threshold. Default is 0.2 |
numProbes |
Number of Probes |
Value
Number of Break points for each unique sample
Fraction Genome Altered
Description
Fraction Genome Altered looks at the fraction of the genome that deviates from a diploid state fga calculates the fraction of the genome altered (FGA; [Chin SF, et. al.](https://www.ncbi.nlm.nih.gov/pubmed/17925008)), measured by taking the sum of the number of bases altered and dividing it by the genome length covered ($G$). Genome length covered was calculated by summing the lengths of each probe on the Affeymetrix 6.0 array. This calculation **excludes** sex chromosomes.
Fraction\ Genome\ Altered =
\frac
{\sum^{R}_{i = 1} d_i}
{G}
\ \ where\ |\bar{y}_{S_i}| \ge 0.2
Usage
fga(cnvData, segmentMean = 0.2, numProbes = NA, genomeSize = 2873203431)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean |
numerical value for the minimum segment_mean cutoff/ threshold. Default is 0.2 |
numProbes |
Number of Probes |
genomeSize |
Size of the genome derived from Affymetrix 6.0 array probe. Default is 2873203431 calculated based on hg38 **excluding sex chromosomes** |
Value
Fraction of the genome altered
Examples
fga(cnvData = maskCNV_BRCA)
Breast Cancer Data from TCGA Data Release 25.0 GDC Product: Data Release Date: July 22, 2020 Masked Copy Number variation data for Breast Cancer for 10 unique samples selected randomly from TCGA
Description
Breast Cancer Data from TCGA Data Release 25.0 GDC Product: Data Release Date: July 22, 2020 Masked Copy Number variation data for Breast Cancer for 10 unique samples selected randomly from TCGA
Usage
data(maskCNV_BRCA)
Format
An object of class dataframe
Source
https://portal.gdc.cancer.gov/
References
Koboldt, D., Fulton, R., McLellan, M. et al. (2012) Nature 490, 61–70 https://www.nature.com/articles/nature11412
Examples
data(maskCNV_BRCA)
tai <- tai(maskCNV_BRCA)
Total Aberration Index
Description
Total Aberration Index calculation takes the sum of lengths of each segment times its segmentation mean for each sample and divides it by the sum of the lengths of each sample.
Usage
tai(cnvData, segmentMean = 0.2, numProbes = NA)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean |
numerical value for the minimum segment_mean cutoff/ threshold. Default is 0.2 |
numProbes |
Number of Probes |
Details
The Total Aberration Index (TAI) (Baumbusch LO, et. al.) is “a measure of the abundance of genomic size of copy number changes in a tumour". It is defined as a weighted sum of the segment means
Total\ Aberration\ Index =
\frac
{\sum^{R}_{i = 1} {d_i} \cdot |{\bar{y}_{S_i}}|}
{\sum^{R}_{i = 1} {d_i}}\ \
where |\bar{y}_{S_i}| \ge |\log_2 1.7|
Value
Average of lengths weighted by segmentation mean for each unique sample
Examples
tai(cnvData = maskCNV_BRCA)
Modified Total Aberration Index
Description
Modified Total Aberration Index calculation takes the sum of lengths of each segment times its segmentation mean for each sample and divides it by the sum of the lengths of each sample.
Usage
taiModified(cnvData, segmentMean = 0, numProbes = NA)
Arguments
cnvData |
dataframe containing following columns: Sample, Start, End, Num_Probes, Segment_Mean |
segmentMean |
numerical value for the minimum segment_mean cutoff/ threshold. Default is 0.2 |
numProbes |
Number of Probes |
Details
Modified Total Aberration Index uses all sample values instead of those in aberrant copy number state, thus does not remove the directionality from the score.
Modified\ Total\ Aberration\ Index =
\frac
{\sum^{R}_{i = 1} {d_i} \cdot {\bar{y}_{S_i}}}
{\sum^{R}_{i = 1} {d_i}}
Value
Average of lengths weighted by segmentation mean for each unique sample
See Also
Examples
taiModified(cnvData = maskCNV_BRCA)