6Y叔的clusterProfiler-book阅读 Chapter 6 KEGG analysis

Chapter 6 KEGG analysis

注释包KEGG.db自2012年起就没有进行过更新,并且在clusterProfiler中,richKEGG(用于KEGG路径分析)richMKEGG(用于KEGG模块分析)支持下载最新的KEGG数据进行富集分析,还可以通过将use_internal_data参数显示设置为TRUE来支持使用KEGG.db。

有了这个功能以后,生物不仅限于先前版本支持的生物,它还可以是在KEGG数据库中的具有KEGG注释数据的任何物种,用户需要将相应名称的缩写传递给生物参数,KEGG支持的生物物种的完整的列表可以通过以下链接进行查询。通过指定的物种,还支持KEGG Orthology(KO)数据库。

clusterProfiler提供了search_kegg-organism()函数,来帮助搜索支持的物种。

library(clusterProfiler)
search_kegg_organism('ece', by='kegg_code')

##     kegg_code                        scientific_name
## 366       ece Escherichia coli O157:H7 EDL933 (EHEC)
##     common_name
## 366        <NA>


ecoli <- search_kegg_organism('Escherichia coli', by='scientific_name')
dim(ecoli)

## [1] 65  3
head(ecoli)

##     kegg_code                        scientific_name
## 361       eco           Escherichia coli K-12 MG1655
## 362       ecj            Escherichia coli K-12 W3110
## 363       ecd            Escherichia coli K-12 DH10B
## 364       ebw                Escherichia coli BW2952
## 365      ecok            Escherichia coli K-12 MDS42
## 366       ece Escherichia coli O157:H7 EDL933 (EHEC)
##     common_name
## 361        <NA>
## 362        <NA>
## 363        <NA>
## 364        <NA>
## 365        <NA>
## 366        <NA>

6.1 KEGG over-representation test

data(geneList, package="DOSE")
gene <- names(geneList)[abs(geneList) > 2]

kk <- enrichKEGG(gene         = gene,
                 organism     = 'hsa',
                 pvalueCutoff = 0.05)
head(kk)


##                ID
## hsa04110 hsa04110
## hsa04114 hsa04114
## hsa04218 hsa04218
## hsa04061 hsa04061
## hsa03320 hsa03320
## hsa04914 hsa04914
##                                                            Description
## hsa04110                                                    Cell cycle
## hsa04114                                                Oocyte meiosis
## hsa04218                                           Cellular senescence
## hsa04061 Viral protein interaction with cytokine and cytokine receptor
## hsa03320                                        PPAR signaling pathway
## hsa04914                       Progesterone-mediated oocyte maturation
##          GeneRatio  BgRatio       pvalue     p.adjust
## hsa04110     11/93 124/7932 1.799177e-07 3.544378e-05
## hsa04114     10/93 128/7932 2.188761e-06 2.155930e-04
## hsa04218     10/93 160/7932 1.613634e-05 9.988265e-04
## hsa04061      8/93 100/7932 2.028074e-05 9.988265e-04
## hsa03320      7/93  76/7932 2.745818e-05 1.081852e-03
## hsa04914      7/93  99/7932 1.502807e-04 4.934216e-03
##                qvalue
## hsa04110 3.465782e-05
## hsa04114 2.108123e-04
## hsa04218 9.766778e-04
## hsa04061 9.766778e-04
## hsa03320 1.057863e-03
## hsa04914 4.824802e-03
##                                                      geneID
## hsa04110 8318/991/9133/890/983/4085/7272/1111/891/4174/9232
## hsa04114    991/9133/983/4085/51806/6790/891/9232/3708/5241
## hsa04218     2305/4605/9133/890/983/51806/1111/891/776/3708
## hsa04061           3627/10563/6373/4283/6362/6355/9547/1524
## hsa03320                 4312/9415/9370/5105/2167/3158/5346
## hsa04914                    9133/890/983/4085/6790/891/5241
##          Count
## hsa04110    11
## hsa04114    10
## hsa04218    10
## hsa04061     8
## hsa03320     7
## hsa04914     7

输入的Gene ID的格式可以是以下格式kegg, ncbi-geneid, ncbi-proteinid or uniprot

6.2 KEGG Gene Set Enrichment Analysis

kk2 <- gseKEGG(geneList     = geneList,
               organism     = 'hsa',
               nPerm        = 1000,
               minGSSize    = 120,
               pvalueCutoff = 0.05,
               verbose      = FALSE)
head(kk2)


##                ID                 Description setSize
## hsa04510 hsa04510              Focal adhesion     188
## hsa04151 hsa04151  PI3K-Akt signaling pathway     322
## hsa03013 hsa03013               RNA transport     131
## hsa05152 hsa05152                Tuberculosis     162
## hsa04062 hsa04062 Chemokine signaling pathway     165
## hsa04218 hsa04218         Cellular senescence     143
##          enrichmentScore       NES      pvalue   p.adjust
## hsa04510      -0.4188582 -1.706291 0.001430615 0.02322097
## hsa04151      -0.3482755 -1.497042 0.002614379 0.02322097
## hsa03013       0.4116488  1.735751 0.003095975 0.02322097
## hsa05152       0.3745153  1.630500 0.003154574 0.02322097
## hsa04062       0.3754101  1.633635 0.003184713 0.02322097
## hsa04218       0.4153718  1.772207 0.003194888 0.02322097
##             qvalues rank                   leading_edge
## hsa04510 0.01576976 2183 tags=27%, list=17%, signal=23%
## hsa04151 0.01576976 1997 tags=23%, list=16%, signal=20%
## hsa03013 0.01576976 3383 tags=40%, list=27%, signal=29%
## hsa05152 0.01576976 2823 tags=34%, list=23%, signal=27%
## hsa04062 0.01576976 1298 tags=21%, list=10%, signal=19%
## hsa04218 0.01576976 1155  tags=17%, list=9%, signal=16%
##                                                                                                                                                                                                                                                                                                                                                                                     core_enrichment
## hsa04510                                                                                                                        5595/5228/7424/1499/4636/83660/7059/5295/1288/23396/3910/3371/3082/1291/394/3791/7450/596/3685/1280/3675/595/2318/3912/1793/1278/1277/1293/10398/55742/2317/7058/25759/56034/3693/3480/5159/857/1292/3908/3909/63923/3913/1287/3679/7060/3479/10451/80310/1311/1101
## hsa04151 627/2252/7059/92579/5563/5295/6794/1288/7010/3910/3371/3082/1291/4602/3791/1027/90993/3441/3643/1129/2322/1975/7450/596/3685/1942/2149/1280/4804/3675/595/2261/7248/2246/4803/3912/1902/1278/1277/2846/2057/1293/2247/55970/5618/7058/10161/56034/3693/4254/3480/4908/5159/1292/3908/2690/3909/8817/9223/4915/3551/2791/63923/3913/9863/3667/1287/3679/7060/3479/80310/1311/5105/2066/1101
## hsa03013                                                                                             10460/1978/55110/54913/9688/8894/11260/10799/9631/4116/5042/8761/6396/23165/8662/10248/55706/79833/9775/29107/23636/5905/9513/5901/10775/10557/4927/79902/1981/26986/11171/10762/8480/8891/11097/26019/10940/4686/9972/81929/10556/3646/9470/387082/1977/57122/8563/7514/79023/3837/9818/56000
## hsa05152                                                                                                      820/51806/6772/64581/3126/3112/8767/3654/1054/1051/3458/1520/11151/1594/50617/54205/91860/8877/3329/637/3689/7096/2207/3929/4360/5603/929/533/3452/6850/7124/1509/3569/7097/1378/8772/64170/3119/843/2213/8625/3920/2215/3587/5594/3593/9103/3592/6300/9114/10333/3109/3108/1432/3552
## hsa04062                                                                                                                                                                                                                  3627/10563/6373/4283/6362/6355/2921/6364/3576/6352/10663/1230/6772/6347/6351/3055/1237/1236/4067/6354/114/3702/6361/1794/1234/6367/6375/6374/2919/409/4793/2792/6360/5880
## hsa04218       

6.3 KEGG Module over-representation test

KEGG模块是手动定义的功能单元的集合,在某些情况下,KEGG模块具有更直接的解释。

mkk <- enrichMKEGG(gene = gene,
                   organism = 'hsa')


6.4 KEGG Module Gene Set Enrichment Analysis

mkk2 <- gseMKEGG(geneList = geneList,
                 organism = 'hsa')

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