导语
GUIDE ╲
由于基因组改变引起的分子损伤的特异性,我们可以生成特征改变谱,称为“signature”。
背景介绍
癌症基因组在其生命周期中由各种突变过程形成,这些过程源于外源性和细胞固有的DNA损伤,以及容易出错的DNA复制,产生了特征突变谱,称为突变特征。sigminer包,帮助用户从基因组改变记录中提取、分析和可视化签名,从而为癌症研究提供新的见解。
R包安装
BiocManager::install("sigminer")
library(sigminer)
结果解析
01
CopyNumber Object
首先用read_copynumber()读取数据,需要是具有以下信息的绝对拷贝数配置文件。
# 加载数据集
load(system.file("extdata", "toy_segTab.RData",
package = "sigminer", mustWork = TRUE
))
cn <- read_copynumber(segTabs,
seg_cols = c("chromosome", "start", "end", "segVal"),
genome_build = "hg19", complement = FALSE, verbose = TRUE
)
Profile
show_cn_profile(cn, nrow = 2, ncol = 1)
show_cn_circos(cn, samples = 1)
show_cn_distribution(cn, mode = "ld")
show_cn_distribution(cn, mode = "cd")
02
Signature Object
操作signature
sig_extract() 或 sig_auto_extract() 的结果是一个带有 Signature 类的列表。
library(maftools)
tcgaAvailable()
set.seed(1234)
#brca <- readRDS("data/BRCA.RDs")
brca <- tcga_load("BRCA")
brca <- subsetMaf(brca,
tsb = as.character(sample(brca@variants.per.sample$Tumor_Sample_Barcode, 100))
)
saveRDS(brca, file = "data/brca.rds")
brca <- readRDS("data/brca.rds")
mt_tally <- sig_tally(
brca,
ref_genome = "BSgenome.Hsapiens.UCSC.hg19",
useSyn = TRUE
)
mt_sig <- sig_unify_extract(mt_tally$nmf_matrix, range = 10, nrun = 10)
sig_signature(mt_sig2)[1:5, ]
show_sig_profile(mt_sig, mode = "SBS", paint_axis_text = FALSE, x_label_angle = 90)
options(sigminer.copynumber.max = 20)
# Load copy number object
load(system.file("extdata", "toy_copynumber.RData",
package = "sigminer", mustWork = TRUE
))
# Use method designed by Wang, Shixiang et al.
cn_tally_W <- sig_tally(cn, method = "W")
sig_w <- sig_extract(cn_tally_W$nmf_matrix, n_sig = 2)
show_sig_profile(sig_w,
mode = "copynumber",
normalize = "feature",
method = "W",
style = "cosmic"
)
show_sig_consensusmap(mt_sig)
03
简单分析流程
数据获取
library(sigminer)
data("simulated_catalogs")
mat <- t(simulated_catalogs$set1)
mat[1:5, 1:5]
提取signature
e1 <- bp_extract_signatures(mat, range = 8:12, n_bootstrap = 5, n_nmf_run = 10)
检查哪个signature号是正确的
bp_show_survey2(e1, highlight = 10)
获取10个signature
obj <- bp_get_sig_obj(e1, 10)
可视化signature文件
show_sig_profile(obj, mode = "SBS", style = "cosmic")
show_sig_exposure(obj, rm_space = TRUE)
计算与 COSMIC 参考signature的相似度
sim <- get_sig_similarity(obj, sig_db = "SBS")
if (require(pheatmap)) {
pheatmap::pheatmap(sim$similarity)
}
小编总结
作为最新发布的突变特征提取和可视化R包,sigminerd的使用是非常简单的,但是一定要注意输入数据的内容要包含关键信息,更加详细的分析流程和使用方法介绍可以参考作者的github链接:
https://github.com/ShixiangWang/sigminer