RNA 40. SCI文章中转录组之筛选候选癌症亚型特异性药物-CSDN博客

本文链接：https://blog.csdn.net/weixin_41368414/article/details/135761779

SubtypeDrug包是一个系统性的生物学工具，用于选择特定癌症亚型的药物，下面我们就看看怎么来实现吧！

简介

癌症可以根据其分子、组织学或临床特征分为不同的亚型。发现针对癌症亚型的药物是个体化医疗的关键一步。SubtypeDrug 是一个系统生物学基于R的软件包，可以根据癌症表达对亚型特异性药物进行优先排序来自许多亚型样本的数据。这提供了一种通过con考虑药物在亚通路水平调节的生物学功能来识别亚型特异性药物的新方法。操作模式包括提取来自生物学途径的亚通路，鉴定由每种药物引起的失调亚通路，推断在样本特异性亚通路活性概况中，评估亚通路上的药物-疾病反向关联水平，通过亚型样本集富集分析鉴定癌症亚型特异性药物，并将结果可视化。它的功能使 SubtypeDrug 能够找到特定于亚型的药物，这将填补该领域的空白最近的工具只能识别针对特定癌症类型的药物。亚型药物可能有助于促进发展为癌症患者量身定制的治疗方案。

SubtypeDrug包是一个系统性的生物学工具，用于选择特定癌症亚型的药物。该工具的主要功能如下：

识别药物调控的亚通路。
推测特定患者的亚通路活性概况。
计算药物-疾病反向关联分数。
选择特定癌症亚型所对应的药物。
结果可视化。

软件包安装

chooseBioCmirror()
if(require(SubtypeDrug))
  BiocManager::install("SubtypeDrug")

if(require(SubtypeDrugData))
  devtools::install_github("hanjunwei-lab/SubtypeDrugData",force = TRUE)

数据读取

这里药物相关的数据我们可以从 SubtypeDrugData 软件包里面下载，例子同样也来自这个数据包。

library(SubtypeDrug)
## Download SubtypeDrugData package from GitHub.
library(SubtypeDrugData)
## Get subpathway list data.  If the gene expression profile contains gene
## Symbol.
data(SpwSymbolList)
## If the gene expression profile contains gene Entrezid.
data(SpwEntrezidList)
## Get drug subpathway association data.
data(DrugSpwData)

实例操作

我们的方法不仅可以在具有多表型分类的数据集中识别癌症亚型特异性药物，还可以在具有癌症和正常样本的数据集中识别癌症相关药物。以模拟乳腺癌数据为例，乳腺癌相关及亚型特异性药物鉴定如下:

require(GSVA)
# > Loading required package: GSVA
require(parallel)
# > Loading required package: parallel Get simulated breast cancer gene
# expression profile data.
Geneexp <- get("Geneexp")
Geneexp[1:5, 1:5]
##          TCGA-BH-A0BZ-11A TCGA-BH-A1FR-11B TCGA-A7-A0DB-11A TCGA-A7-A0CH-11A
## PMPCB            18.00481         18.07167         18.18495         18.16765
## WISP2            19.51181         18.44486         19.45742         19.00089
## IQCB1            17.23446         17.15936         16.67831         17.38432
## ARHGAP17         17.62721         17.21063         17.86861         17.45563
## BCL7C            17.01795         17.03588         17.40710         18.00261
##          TCGA-E9-A1RD-11A
## PMPCB            18.20920
## WISP2            19.91755
## IQCB1            16.83018
## ARHGAP17         17.51310
## BCL7C            17.25346
## Obtain sample subtype data and calculate breast cancer subtype-specific
## drugs.
Subtype_labels <- system.file("extdata", "Subtype_labels.cls", package = "SubtypeDrug")

# Identify breast subtype-specific drugs.
Subtype_drugs<-PrioSubtypeDrug(Geneexp,Subtype_labels,"Control",SpwSymbolList,
                               drug.spw.data=DrugSpwData,E_FDR=1,S_FDR=1)

PrioSubtypeDrug()函数也只能在乳腺癌和正常两种类型的样本中识别乳腺癌相关药物。

## Results display.
Cancer_normal_labels <- system.file("extdata", "Cancer_normal_labels.cls", package = "SubtypeDrug")
Disease_drugs <- PrioSubtypeDrug(Geneexp, Cancer_normal_labels, "Control", SpwSymbolList,
    drug.spw.data = DrugSpwData, E_FDR = 1, S_FDR = 1)

PrioSubtypeDrug()函数也支持用户定义的数据。

## User-defined drug regulation data should resemble the structure below.
UserDS <- get("UserDS")
str(UserDS[1:5])
## List of 5
##  $ 1,5-isoquinolinediol(1e-04M):List of 2
##   ..$ Target_upregulation  : chr [1:64] "00140_10" "00450_2" "00590_2" "00830_2" ...
##   ..$ Target_downregulation: chr [1:76] "00030_2" "00071_1" "00100_2" "00100_5" ...
##  $ 2-deoxy-D-glucose(0.01M)    :List of 2
##   ..$ Target_upregulation  : chr [1:68] "00250_1" "01524_2" "03013_1" "03015_4" ...
##   ..$ Target_downregulation: chr [1:43] "00051_1" "00100_6" "00230_1" "00240_8" ...
##  $ NA                          : NULL
##  $ NA                          : NULL
##  $ NA                          : NULL
## Need to load gene set data consistent with drug regulation data.
UserGS <- get("UserGS")
str(UserGS[1:5])
## List of 5
##  $ 00140_10: chr [1:49] "CYP11A1" "HSD3B1" "HSD3B2" "CYP17A1" ...
##  $ 00250_1 : chr [1:17] "NIT2" "ASNS" "NAT8L" "IL4I1" ...
##  $ 00030_2 : chr [1:28] "GPI" "DERA" "PRPS1L1" "PRPS1" ...
##  $ 00071_1 : chr [1:17] "ACADSB" "ACADS" "EHHADH" "HADH" ...
##  $ 00100_2 : chr [1:8] "EBP" "DHCR7" "SC5D" "DHCR24" ...
Drugs <- PrioSubtypeDrug(Geneexp, Subtype_labels, "Control", UserGS, spw.min.sz = 1,
    drug.spw.data = UserDS, drug.spw.min.sz = 1, E_FDR = 1, S_FDR = 1)
## Estimating GSVA scores for 17 gene sets.
## Estimating ECDFs with Gaussian kernels
## 
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结果可视化

绘制癌症样本标准化药物-疾病反向关联评分的热图

require(pheatmap)
## Heat map of normalized disease-drug reverse association scores for all
## subtype-specific drugs.
plotDScoreHeatmap(data = Subtype_drugs, E_Pvalue.th = 0.05, E_FDR.th = 1, S_Pvalue.th = 0.05,
    S_FDR.th = 1, show.colnames = FALSE)

## Plot only Basal subtype-specific drugs.
plotDScoreHeatmap(Subtype_drugs, subtype.label = "Basal", SDS = "all", E_Pvalue.th = 0.05,
    E_FDR.th = 1, S_Pvalue.th = 0.05, S_FDR.th = 1, show.colnames = FALSE)

## Plot a heat map of the individualized activity aberrance scores of
## subpathway regulated by drug pirenperone(1.02e-05M).  Basal-specific drugs
## pirenperone(1.02e-05M) regulated subpathways that show opposite activity
## from normal samples.
plotDSpwHeatmap(data = Subtype_drugs, drug.label = "pirenperone(1.02e-05M)", subtype.label = "Basal",
    show.colnames = FALSE)

绘制药物的分布图

## Plot a global graph of the Basal-specific drug pirenperone(1.02e-05M).
plotGlobalGraph(data = Subtype_drugs, drug.label = "pirenperone(1.02e-05M)")

绘制网络图

require(igraph)
# plot network graph of the subpathway 00020_4.
plotSpwNetGraph(spwid = "00020_4")

可视化药物的化学结构

require(ChemmineR)
require(rvest)
## Plot the chemical structure of drug pirenperone.
Chem_str <- getDrugStructure(drug.label = "pirenperone")
plot(Chem_str)

## $pirenperone
## An instance of "SDF"
## 
## <<header>>
##                             Molecule_Name 
##                                    "4847" 
##                                    Source 
##                  "  -OEChem-01212420182D" 
##                                   Comment 
##                                        "" 
##                               Counts_Line 
## " 53 56  0     0  0  0  0  0  0999 V2000" 
## 
## <<atomblock>>
##           C1      C2  C3  C5  C6  C7  C8  C9 C10 C11 C12 C13 C14 C15 C16
## F_1  14.1923  0.7327   0   0   0   0   0   0   0   0   0   0   0   0   0
## O_2  10.7282 -2.2673   0   0   0   0   0   0   0   0   0   0   0   0   0
## ...      ...     ... ... ... ... ... ... ... ... ... ... ... ... ... ...
## H_52  1.4643  0.3998   0   0   0   0   0   0   0   0   0   0   0   0   0
## H_53  1.4643  2.0656   0   0   0   0   0   0   0   0   0   0   0   0   0
## 
## <<bondblock>>
##      C1  C2  C3  C4  C5  C6  C7
## 1     1  26   1   0   0   0   0
## 2     2  13   2   0   0   0   0
## ... ... ... ... ... ... ... ...
## 55   28  52   1   0   0   0   0
## 56   29  53   1   0   0   0   0
## 
## <<datablock>> (34 data items)
##                                    
## "4847" "4847" "4847" "4847"  "..."

Reference

Han X, Kong Q, Liu C, Cheng L, Han J. SubtypeDrug: a software package for prioritization of candidate cancer subtype-specific drugs. Bioinformatics. 2021 Aug 25;37(16):2491-2493. doi: 10.1093/bioinformatics/btab011. PMID: 33459772.