Hi all,

I have codes to download updated KEGG pathways that I have run thousands of times that now fail with an error. Here is a reproducible example using kegga():

> library(limma)
> library(Mus.musculus)
Loading required package: AnnotationDbi
#... deleted for space
> univ_EG <- keys(Mus.musculus, keytype = "ENTREZID")
> sel_EG <- univ_EG[200:1200]
> kegg_out <- kegga(sel_EG, universe = univ_EG, 
+                         species.KEGG = "mmu")
Error in scan(file = file, what = what, sep = sep, quote = quote, dec = dec,  : 
  cannot read from connection
In addition: Warning message:
In scan(file = file, what = what, sep = sep, quote = quote, dec = dec,  :
  URL 'https://rest.kegg.jp/link/pathway/mmu': status was 'Failure when receiving data from the peer'

I went to KEGG and this notice was posted that KEGG API moving to HTTPS as of June 1, 2022: https://www.genome.jp/kegg/docs/announce.html . I think this may be the cause of my problem and also this recent post KEGG Pathway in R . Anyone know what settings I need to change?

Thanks, Jenny

sessionInfo( )
R version 4.2.0 (2022-04-22 ucrt)
Platform: x86_64-w64-mingw32/x64 (64-bit)
Running under: Windows 10 x64 (build 19044)

Matrix products: default

locale:
[1] LC_COLLATE=English_United States.utf8 
[2] LC_CTYPE=English_United States.utf8   
[3] LC_MONETARY=English_United States.utf8
[4] LC_NUMERIC=C                          
[5] LC_TIME=English_United States.utf8    

attached base packages:
[1] stats4    stats     graphics  grDevices utils     datasets  methods  
[8] base     

other attached packages:
 [1] Mus.musculus_1.3.1                       
 [2] TxDb.Mmusculus.UCSC.mm10.knownGene_3.10.0
 [3] org.Mm.eg.db_3.15.0                      
 [4] GO.db_3.15.0                             
 [5] OrganismDbi_1.38.0                       
 [6] GenomicFeatures_1.48.0                   
 [7] GenomicRanges_1.48.0                     
 [8] GenomeInfoDb_1.32.1                      
 [9] AnnotationDbi_1.58.0                     
[10] IRanges_2.30.0                           
[11] S4Vectors_0.34.0                         
[12] Biobase_2.56.0                           
[13] BiocGenerics_0.42.0                      
[14] limma_3.52.0                             

loaded via a namespace (and not attached):
 [1] MatrixGenerics_1.8.0        httr_1.4.3                 
 [3] bit64_4.0.5                 assertthat_0.2.1           
 [5] BiocManager_1.30.18         BiocFileCache_2.4.0        
 [7] RBGL_1.72.0                 blob_1.2.3                 
 [9] GenomeInfoDbData_1.2.8      Rsamtools_2.12.0           
[11] yaml_2.3.5                  progress_1.2.2             
[13] pillar_1.7.0                RSQLite_2.2.13             
[15] lattice_0.20-45             glue_1.6.2                 
[17] digest_0.6.29               XVector_0.36.0             
[19] Matrix_1.4-1                XML_3.99-0.9               
[21] pkgconfig_2.0.3             biomaRt_2.52.0             
[23] zlibbioc_1.42.0             purrr_0.3.4                
[25] BiocParallel_1.30.0         tibble_3.1.6               
[27] KEGGREST_1.36.0             generics_0.1.2             
[29] ellipsis_0.3.2              cachem_1.0.6               
[31] SummarizedExperiment_1.26.0 cli_3.3.0                  
[33] magrittr_2.0.3              crayon_1.5.1               
[35] memoise_2.0.1               fansi_1.0.3                
[37] xml2_1.3.3                  graph_1.74.0               
[39] tools_4.2.0                 prettyunits_1.1.1          
[41] hms_1.1.1                   BiocIO_1.6.0               
[43] lifecycle_1.0.1             matrixStats_0.62.0         
[45] stringr_1.4.0               DelayedArray_0.22.0        
[47] Biostrings_2.64.0           compiler_4.2.0             
[49] rlang_1.0.2                 grid_4.2.0                 
[51] RCurl_1.98-1.6              rstudioapi_0.13            
[53] rjson_0.2.21                rappdirs_0.3.3             
[55] bitops_1.0-7                restfulr_0.0.13            
[57] DBI_1.1.2                   curl_4.3.2                 
[59] R6_2.5.1                    GenomicAlignments_1.32.0   
[61] dplyr_1.0.9                 rtracklayer_1.56.0         
[63] fastmap_1.1.0               bit_4.0.4                  
[65] utf8_1.2.2                  filelock_1.0.2             
[67] stringi_1.7.6               parallel_4.2.0             
[69] Rcpp_1.0.8.3                vctrs_0.4.1                
[71] png_0.1-7                   dbplyr_2.1.1               
[73] tidyselect_1.1.2

Yes you're right, the move to https has caused the error. Just reinstall limma -- the issue is fixed in limma 3.52.2.

The issue is system and R version dependent. It depends on whether the system is tolerant of reading https as if it was http. In Windows, the issue only appears in R 4.2.X and not in R 4.1.X. In Linux, the issue doesn't appear at all. On the Mac, the issue appears even in R 4.1.X.

If you updated the KEGGREST package there was a PR to correct this as well in version 1.36.2