2.C: miEEA & rbioapi

Moosa Rezwani

2025-02-07

1 Introduction

The miRNA Enrichment Analysis and Annotation Tool (miEAA) is a service provided by the Chair for Clinical Bioinformatics at Saarland University. Basically, miEAA is a multi-species microRNA enrichment analysis tool. For more information, see their website or published paper.


2 First, find enrichment categories

Before Performing enrichment analysis on a miRNA set, note that based on your input miRNA type (either all mature or precursor, not a mixture of both!) and the species, there will be different sets of supported enrichment categories.

Thus, it is recommended to retrieve a list of possible enrichment categories that you may use:

## A list of available enrichment categories for:

## mature human miRNA:
rba_mieaa_cats(mirna_type = "mature", species = 9606)

## precursor human miRNA
rba_mieaa_cats(mirna_type = "precursor", species = 9606)

## precursor zebrafish miRNA
rba_mieaa_cats(mirna_type = "mature", species = "Danio rerio")

3 Submit Enrichment analysis request to miEAA

There are two approaches to do this, we will start with the simpler one.

3.1 Approach 1: Using the Wrapper function

Just fill the arguments of rba_mieaa_enrich() according to the function’s manual; As you can see in the function’s arguments, you have a lot of controls over your enrichment request, but you need to provide test_set, mirna_type, test_type, and species:

## 1 We create a variable with our miRNAs' mature IDs
mirs <- c(
  "hsa-miR-20b-5p", "hsa-miR-144-5p", "hsa-miR-17-5p", "hsa-miR-20a-5p",
  "hsa-miR-222-3p", "hsa-miR-106a-5p", "hsa-miR-93-5p", "hsa-miR-126-3p",
  "hsa-miR-363-3p", "hsa-miR-302c-3p", "hsa-miR-374b-5p", "hsa-miR-18a-5p",
  "hsa-miR-548d-3p", "hsa-miR-135a-3p", "hsa-miR-558", "hsa-miR-130b-5p",
  "hsa-miR-148a-3p"
)

## 2a We can perform enrichment analysis on our miRNA set without limiting the analysis to any categories
mieaa_all <- rba_mieaa_enrich(
  test_set = mirs,
  mirna_type = "mature",
  test_type = "ORA",
  species = 9606
)
#>  -- Step 1/3: Submitting Enrichment analysis request:
#> No categories were supplied, Requesting enrichment using all of the 32 available categories for species 'Homo sapiens'.
#> Submitting ORA enrichment request for 17 miRNA IDs of species Homo sapiens to miEAA servers.
#> 
#>  -- Step 2/3: Checking for Submitted enrichment analysis's status every 5 seconds.
#>     Your submitted job ID is: 31443fed-d459-408e-ad31-a65e078d7560
#> ............
#> 
#>  -- Step 3/3: Retrieving the results.
#> Retrieving results of submitted enrichment request with ID: 31443fed-d459-408e-ad31-a65e078d7560

## 2b Or, We can limit the enrichment to certain datasets (enrichment categories)
mieaa_kegg <- rba_mieaa_enrich(
  test_set = mirs,
  mirna_type = "mature",
  test_type = "ORA",
  species = 9606,
  categories = "KEGG_mature"
)
#>  -- Step 1/3: Submitting Enrichment analysis request:
#> Submitting ORA enrichment request for 17 miRNA IDs of species Homo sapiens to miEAA servers.
#> 
#>  -- Step 2/3: Checking for Submitted enrichment analysis's status every 5 seconds.
#>     Your submitted job ID is: c81bd6d0-f5af-41a9-8ef4-2bab0139c1a4
#> .
#> 
#>  -- Step 3/3: Retrieving the results.
#> Retrieving results of submitted enrichment request with ID: c81bd6d0-f5af-41a9-8ef4-2bab0139c1a4

3.2 Approach 2: Going step-by-step

As stated before, rba_mieaa_enrich() is a wrapper function, meaning that it executes the following sequence of functions:

## 1 Submit enrichment request to miEAA
request <- rba_mieaa_enrich_submit(
  test_set = mirs,
  mirna_type = "mature",
  test_type = "ORA",
  species = 9606,
  categories = c("miRWalk_Diseases_mature", "miRWalk_Organs_mature")
)

## 2 check for job's running status
rba_mieaa_enrich_status(job_id = request$job_id)

## 3 If the job has completed, retrieve the results
results <- rba_mieaa_enrich_results(job_id = request$job_id)

Please Note: Other services supported by rbioapi also provide Over-representation analysis tools. Please see the vignette article Do with rbioapi: Over-Representation (Enrichment) Analysis in R (link to the documentation site) for an in-depth review.


4 Convert miRNA accessions

miEAA only recognizes miRBASE version 22 accessions. You can use rba_mieaa_convert_version() to convert miRNA accession between different miRBASE versions. Also, as stated before, miEAA differentiate between precursor and mature miRNA accessions, to convert between these 2 accession types, use rba_mieaa_convert_type().


5 How to Cite?

To cite miEAA (Please see https://ccb-compute2.cs.uni-saarland.de/mieaa2/):

To cite rbioapi:


7 Session info

#> R version 4.4.2 (2024-10-31 ucrt)
#> Platform: x86_64-w64-mingw32/x64
#> Running under: Windows 11 x64 (build 26100)
#> 
#> Matrix products: default
#> 
#> 
#> locale:
#> [1] LC_COLLATE=C                          
#> [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    
#> 
#> time zone: Europe/Brussels
#> tzcode source: internal
#> 
#> attached base packages:
#> [1] stats     graphics  grDevices utils     datasets  methods   base     
#> 
#> other attached packages:
#> [1] rbioapi_0.8.2
#> 
#> loaded via a namespace (and not attached):
#>  [1] digest_0.6.37     R6_2.5.1          fastmap_1.2.0     xfun_0.50        
#>  [5] magrittr_2.0.3    cachem_1.1.0      knitr_1.49        htmltools_0.5.8.1
#>  [9] png_0.1-8         rmarkdown_2.29    lifecycle_1.0.4   DT_0.33          
#> [13] cli_3.6.3         grid_4.4.2        sass_0.4.9        jquerylib_0.1.4  
#> [17] compiler_4.4.2    httr_1.4.7        rstudioapi_0.17.1 tools_4.4.2      
#> [21] curl_6.1.0        evaluate_1.0.3    bslib_0.8.0       yaml_2.3.10      
#> [25] htmlwidgets_1.6.4 rlang_1.1.4       jsonlite_1.8.9    crosstalk_1.2.1