miRNAmeConverter-vignette

In miRNAmeConverter: Convert miRNA Names to Different miRBase Versions

The miRBase database [@Griffiths-Jones01012004; @Griffiths-Jones01012006; @Griffiths-Jones01012008; @Kozomara01012011; @Kozomara01012014] is the official repository for miRNAs and includes a miRNA naming convention [@AMBROS01032003; @meyers2008criteria]. Over the years of development miRNAs have been added to, or deleted from the database, while some miRNA names have been changed. As a result, each version of the miRBase database can differ substantially from previous versions. If working with just one or two miRNAs, these can be manually searched on the miRBase website. With larger sets of miRNAs, however, this work becomes labour intensive and prone to mistakes. When working with a set of miRNAs, therefore, useful information includes

• if a certain miRNA name exists in the miRBase database.
• the miRNA sequence in a certain miRBase version.
• if a given miRNA is still considered to be a miRNA.
• the miRNA names from the most recent miRBase version
• the respective miRNA name from a different miRBase version, for using other services, such as miRNA target databases.

The miRNAmeConverter R package has been developed for handling naming challenges of mature miRNAs.

In addition we have developed a web interface that enables one to use the translateMiRNAName function via web interface and is based on shiny (miRNAmeConverter-web).

1. Introduction

The miRNAmeConverter package delivers results in a fast and transparent way. The main functions

• check for validity of mature miRNA names,
• determine the most likely miRBase version of a given set of miRNAs and
• translate mature miRNA names to different versions (incl. sequences).

The core function, translating miRNA names to different versions, is especially useful when dealing with miRNA tools other than miRBase. To retrieve targets from miRTarBase, for example, the miRNA name from version 20 is required, whereas the website miRecords only accepts version 17. The miRNAmeConverter can manage large sets of miRNA names and hence can be easily implemented into workflows.

The data set included in the package (miRNAs) is a collection of human miRNA names. It consists of valid miRNA names (some duplicates), incorrect names and features used as controls in experiments, such as the RNU44 as a house keeping gene for HT-qPCR assay plates from Applied Biosystems.

To load the package and gain access to the functions and sample dataset of the miRNAmeConverter package just run the following command:

library(miRNAmeConverter)

Citing miRNAmeConverter

To give the authors professional credit for their work, please try to cite the publication when you use the miRNAmeConverter:

citation("miRNAmeConverter")

Vignette Info

This vignette has been generated using an R Markdown file with knitr:rmarkdown as vignette engine [@bibtex; @knitr1; @knitr2; @knitr3; @knitcitations].

Database information

The data used in the miRNAmeConverter package is obtained from the miRBaseVersions.db annotation package [@mirbaseversionscite].

miRNA name input values

According to the nomenclature used in the miRBase repository hsa-mir-29a is a stem-loop sequence name. If we substitute the 'r' by a capital 'R' it codes for the mature 3' miRNA hsa-miR-29a (or hsa-miR-29a-5p in the current version). The miRNAs input value for the functions has to be in form of a character vector. Algorithms of the package are not case sensitive. This has the effect, that for example in the case hsa-mir-29a and hsa-miR-29a as input values both will be considered as valid mature miRNA names.

2. The MiRNANameConverter class

The MiRNANameConverter class is coded in S4 style. All functions offered by the miRNAmeConverter package are methods of that class. The following figure is a simplified class diagram with the exported methods and class attributes:

All methods can be displayed by

ls("package:miRNAmeConverter");

The slot names (attributes) of the class can be displayed by

slotNames("MiRNANameConverter");

An instance of the MiRNANameConverter class can be created by calling the MiRNANameConverter function:

MiRNANameConverter();

3. Use Cases

3.1 Check for valid miRNA name

Valid input values

We have given a set of mature miRNA names miRNAs and would like to check if the names are actual miRNA names that are or were listed in any miRBase version. Our miRNAs have the following values:

miRNAs = c("hsa-miR-422b", "mmu-mir-872", "gra-miR157b", "cel-miR-56*");

Our first step is to create an instance of the MiRNANameConverter class by calling the constructor and saving it to the variable nc.

nc = MiRNANameConverter();

Now we check if the names are valid names listed in any of the provided miRBase versions:

checkMiRNAName(nc, miRNAs);

Mixed input values

The following set of miRNA names contains valid as well as invalid names.

# "RNU-6" and "bpcv1-miR-B23" are not valid
miRNAs = c("hsa-miR-422b", "RNU-6", "mmu-miR-872", "gra-miR157b", "bpcv1-miR-B23", "bpcv1-miR-B1");
nc = MiRNANameConverter();    # Create MiRNANameConverter object
checkMiRNAName(nc, miRNAs);   # check names

This time the function prints information for the features that did not pass the check and therefore are not included in the return value.

3.2 Assess most likely miRBase version

Sometimes it is useful to know the miRBase version that a given set of miRNA names is from. In this case one can use the assessVersion function to receive the most likely miRBase version. The following example makes use of the provided example-miRNAs-dataset.

nc = MiRNANameConverter();             # Create MiRNANameConverter object
assessVersion(nc, example.miRNAs);     # Assess most likely miRBase version

The console output shows that from the r length(example.miRNAs) input names there were r length(unique(example.miRNAs)) unique values. Five of these values are not listed in any miRBase version and were neglected. The return value is a data.frame object with the two columns version and frequency. It is ordered by frequency and version. It shows that 347 out of 350 valid input miRNAs could be assigned to miRBase version 9.0. This is the highest score and therefore the most likely miRBase version of the input mature miRNA names.

3.3 Translate miRNA name(s) and their sequence(s)

Translating miRNA names to different versions is the most required function. Let us assume we found a paper that shows that the miRNA "hsa-miR-422b" is significantly differentially expressed under certain conditions. Assume further, that we did a similar experiment but this miRNA does not show up in our analysis. Instead we got "hsa-miR-378a-3p" from miRBase version 21. We see, that the previous paper was released a couple of years ago so there might be a chance that their miRNA could now run under a different name. We apply the translateMiRNAName function with hsa-miR-422b as miRNA parameter and no version. With no given version the function returns the miRBase version 21 by default.

miRNA.paper = "hsa-miR-422b";
nc = MiRNANameConverter();             # Create MiRNANameConverter object
translateMiRNAName(nc, miRNA.paper);   # Translate miRNA names

The result shows that these two miRNAs are actually the same. This is because "hsa-miR-422b" is last listed in miRBase version 9.2. In version 10.0 it was named "hsa-miR-378" which in the current version 21.0 runs under the name "hsa-miR-378a-3p".

Another example with more diverse input names is shown below, with the respective console output and the entry in the attribute description.

miRNAs = c("hsa-miR-128b", "hsa-miR-213", "mmu-miR-302b*", 
           "mmu-miR-872", "ebv-miR-BART5", "bpcv1-miR-B23");
nc = MiRNANameConverter();              # Create MiRNANameConverter object
result = translateMiRNAName(            # Translate names
                            nc
                            ,miRNAs
                            ,sequenceFormat = 1
                            ,versions = c(8, 8.1, 18, 21)
                            );        

The console output shows us that one of the input values is not a miRNA ("bpcv1-miR-B23") and another is not listed in miRBase version 21 ("hsa-miR-128b").

result;

Attribute description

The information, whether a miRNA is OK or not, is stored in form of an attribute of the return value of the function. This data.frame object provides information about every single input value and can be accessed via the attr command followed by 'description'.

attr(result, 'description');

Attribute sequences

Sometimes it can be useful to confirm the sequence of miRNAs for selected miRBase versions. In such a case all we have to do is checking out the sequence attribute of our translation result.

attr(result, 'sequence');

Due to the fact that we called the translateMiRNAName function with the parameter sequenceFormat = 1 the attribute only contains the sequence for each version respectively. If we would like to have miRNA name and sequence combined in one table we can call the translateMiRNAName function with sequenceFormat = 2.

result = translateMiRNAName(            # Translate names
                            nc
                            ,miRNAs
                            ,sequenceFormat = 2
                            ,versions = c(17, 19, 21)
                            );
attr(result, 'sequence');

3.4 Other functions

Save translation results

Sometimes it is useful to save a variable to a file. Taking the translation result from above we can do so by running the following command with default settings:

saveResults(nc, result);

Three files will be saved, the miRNA name translation result, the description and sequence. By default the files are tab-separated files without the parameter quote set to FALSE. Other options can be applied and will be passed on to the utils::write.table function.

Getter functions

Other functions are so called getter-functions to receive the values of the class attributes current.version and valid.versions respectively.

nc = MiRNANameConverter();   # Create MiRNANameConverter object
currentVersion(nc);          # Receive the maximum miRBase version included in the package
validVersions(nc);           # Receive all valid versions
nOrganisms(nc);              # Number of organisms
validOrganisms(nc);          # Valid organisms

Additional information

Packages loaded via namespace

The following packages are used in the miRNAmeConverter package:

• AnnotationDbi_1.32.3 [@annotdbicite]
• miRBaseVersions.db annotation package [@mirbaseversionscite]
• RSQLite_1.0.0 [@rsqlitecite]
• tools_3.2.5 [@toolscite]

Future Aspects

This tool can only offer good functionality if it will be kept up to date. Therefore we plan to include new miRBase releases as soon as possible.

References {-}

miRNAmeConverter documentation built on Nov. 8, 2020, 5:36 p.m.