An R interface to the MEME Suite family of tools, which provides several utilities for performing motif analysis on DNA, RNA, and protein sequences. memes works by detecting a local install of the MEME suite, running the commands, then importing the results directly into R.
memes is currently available on the Bioconductor devel
branch:
if (!requireNamespace("BiocManager", quietly = TRUE))
install.packages("BiocManager")
# The following initializes usage of Bioc devel
BiocManager::install(version='devel')
BiocManager::install("memes")
You can install the development version of memes from GitHub with:
if (!requireNamespace("remotes", quietly=TRUE))
install.packages("remotes")
remotes::install_github("snystrom/memes")
# To temporarily bypass the R version 4.1 requirement, you can pull from the following branch:
remotes::install_github("snystrom/memes", ref = "no-r-4")
# Get development version from dockerhub
docker pull snystrom/memes_docker:devel
# the -v flag is used to mount an analysis directory,
# it can be excluded for demo purposes
docker run -e PASSWORD=<password> -p 8787:8787 -v <path>/<to>/<project>:/mnt/<project> snystrom/memes_docker:devel
memes relies on a local install of the MEME Suite. For installation instructions for the MEME suite, see the MEME Suite Installation Guide.
memes needs to know the location of the meme/bin/
directory on your
local machine. You can tell memes the location of your MEME suite
install in 4 ways. memes will always prefer the more specific definition
if it is a valid path. Here they are ranked from most- to
least-specific:
meme_path
argument of all
memes functionsoptions(meme_bin = "/path/to/meme/bin/")
inside your R scriptMEME_BIN=/path/to/meme/bin/
in your .Renviron
file~/meme/bin/
If memes fails to detect your install at the specified location, it will fall back to the next option.
To verify memes can detect your MEME install, use check_meme_install()
which uses the search herirarchy above to find a valid MEME install. It
will report whether any tools are missing, and print the path to MEME
that it sees. This can be useful for troubleshooting issues with your
install.
library(memes)
# Verify that memes detects your meme install
# (returns all green checks if so)
check_meme_install()
#> checking main install
#> ✓ /opt/meme/bin
#> checking util installs
#> ✓ /opt/meme/bin/dreme
#> ✓ /opt/meme/bin/ame
#> ✓ /opt/meme/bin/fimo
#> ✓ /opt/meme/bin/tomtom
#> ✓ /opt/meme/bin/meme
#> x /opt/meme/bin/streme
# You can manually input a path to meme_path
# If no meme/bin is detected, will return a red X
check_meme_install(meme_path = 'bad/path')
#> checking main install
#> x bad/path
| Function Name | Use | Sequence Input | Motif Input | Output |
|:-------------:|:------------------------------:|:--------------:|:-----------:|:-----------------------------------------------------------------|
| runStreme()
| Motif Discovery (short motifs) | Yes | No | universalmotif_df
|
| runDreme()
| Motif Discovery (short motifs) | Yes | No | universalmotif_df
|
| runAme()
| Motif Enrichment | Yes | Yes | data.frame (optional: sequences
column) |
| runFimo()
| Motif Scanning | Yes | Yes | GRanges of motif positions |
| runTomTom()
| Motif Comparison | No | Yes | universalmotif_df
w/ best_match_motif
and tomtom
columns* |
| runMeme()
| Motif Discovery (long motifs) | Yes | No | universalmotif_df
|
* Note: if runTomTom()
is run using a universalmotif_df
the
results will be joined with the universalmotif_df
results as extra
columns. This allows easy comparison of de-novo discovered motifs with
their matches.
Sequence Inputs can be any of:
Biostrings::XStringSet
(can be generated from GRanges using
get_sequence()
helper function)Biostrings::XStringSet
objects (generated by
get_sequence()
)Motif Inputs can be any of:
universalmotif
object, or list of universalmotif
objectsrunDreme()
results object (this allows the results of
runDreme()
to pass directly to runTomTom()
)list()
(e.g. list("path/to/database.meme", "dreme_results" = dreme_res)
)Output Types:
runDreme()
, runStreme()
, runMeme()
and runTomTom()
return
universalmotif_df
objects which are data.frames with special columns.
The motif
column contains a universalmotif
object, with 1 entry per
row. The remaining columns describe the properties of each returned
motif. The following column names are special in that their values are
used when running update_motifs()
and to_list()
to alter the
properties of the motifs stored in the motif
column. Be careful about
changing these values as these changes will propagate to the motif
column when calling update_motifs()
or to_list()
.
memes is built around the universalmotif
package
which provides a framework for manipulating motifs in R.
universalmotif_df
objects can interconvert between data.frame and
universalmotif
list format using the to_df()
and to_list()
functions, respectively. This allows use of memes
results with all
other Bioconductor motif packages, as universalmotif
objects can
convert to any other motif type using convert_motifs()
.
runTomTom()
returns a special column: tomtom
which is a data.frame
of all match data for each input motif. This can be expanded out using
tidyr::unnest(tomtom_results, "tomtom")
, and renested with
nest_tomtom()
. The best_match_
prefixed columns returned by
runTomTom()
indicate values for the motif which was the best match to
the input motif.
suppressPackageStartupMessages(library(magrittr))
suppressPackageStartupMessages(library(GenomicRanges))
# Example transcription factor peaks as GRanges
data("example_peaks", package = "memes")
# Genome object
dm.genome <- BSgenome.Dmelanogaster.UCSC.dm6::BSgenome.Dmelanogaster.UCSC.dm6
The get_sequence
function takes a GRanges
or GRangesList
as input
and returns the sequences as a BioStrings::XStringSet
, or list of
XStringSet
objects, respectively. get_sequence
will name each fasta
entry by the genomic coordinates each sequence is from.
# Generate sequences from 200bp about the center of my peaks of interest
sequences <- example_peaks %>%
resize(200, "center") %>%
get_sequence(dm.genome)
runDreme()
accepts XStringSet or a path to a fasta file as input. You
can use other sequences or shuffled input sequences as the control
dataset.
# runDreme accepts all arguments that the commandline version of dreme accepts
# here I set e = 50 to detect motifs in the limited example peak list
# In a real analysis, e should typically be < 1
dreme_results <- runDreme(sequences, control = "shuffle", e = 50)
memes is built around the
universalmotif
package. The results are returned in universalmotif_df
format, which
is an R data.frame that can seamlessly interconvert between data.frame
and universalmotif
format using to_list()
to convert to
universalmotif
list format, and to_df()
to convert back to
data.frame format. Using to_list()
allows using memes
results with
all universalmotif
functions like so:
library(universalmotif)
dreme_results %>%
to_list() %>%
view_motifs()
Discovered motifs can be matched to known TF motifs using runTomTom()
,
which can accept as input a path to a .meme formatted file, a
universalmotif
list, or the results of runDreme()
.
TomTom uses a database of known motifs which can be passed to the
database
parameter as a path to a .meme format file, or a
universalmotif
object.
Optionally, you can set the environment variable MEME_DB
in
.Renviron
to a file on disk, or the meme_db
value in options
to a
valid .meme format file and memes will use that file as the database.
memes will always prefer user input to the function call over a global
variable setting.
options(meme_db = system.file("extdata/flyFactorSurvey_cleaned.meme", package = "memes"))
m <- create_motif("CMATTACN", altname = "testMotif")
tomtom_results <- runTomTom(m)
tomtom_results
#> motif name altname consensus alphabet strand icscore type
#> 1 <mot:motif> motif testMotif CMATTACN DNA +- 13 PPM
#> bkg best_match_name best_match_altname
#> 1 0.25, 0.25, 0.25, 0.25 prd_FlyReg prd
#> best_db_name best_match_offset best_match_pval best_match_eval
#> 1 flyFactorSurvey_cleaned 0 9.36e-05 0.052
#> best_match_qval best_match_strand
#> 1 0.0353 +
#> best_match_motif
#> 1 <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>
#> tomtom
#> 1 prd_FlyReg, tup_SOLEXA_10, CG13424_Cell, CG11085_Cell, BH2_Cell, CG13424_SOLEXA_2, Tup_Cell, Tup_SOLEXA, Bsh_Cell, Exex_SOLEXA, Odsh_SOLEXA, Unc4_Cell, Ubx_FlyReg, Unc4_SOLEXA, E5_Cell, inv_SOLEXA_5, BH2_SOLEXA, Zen_SOLEXA, CG33980_SOLEXA_2_10, BH1_SOLEXA, CG33980_SOLEXA_2_0, Hgtx_Cell, NK7.1_Cell, Slou_Cell, CG13424_SOLEXA, Zen2_Cell, AbdA_SOLEXA, Antp_SOLEXA, Btn_Cell, Dfd_SOLEXA, Eve_SOLEXA, Ftz_Cell, Hmx_SOLEXA, Hmx_Cell, CG34031_Cell, zen2_SOLEXA_2, En_Cell, Pb_SOLEXA, Slou_SOLEXA, Unpg_Cell, inv_SOLEXA_2, ovo_FlyReg, lim_SOLEXA_2, C15_SOLEXA, Ems_Cell, Btn_SOLEXA, Unpg_SOLEXA, Pb_Cell, Bsh_SOLEXA, Scr_SOLEXA, Zen2_SOLEXA, CG34031_SOLEXA, Eve_Cell, Pph13_Cell, BH1_Cell, CG11085_SOLEXA, CG32532_Cell, en_FlyReg, Dll_SOLEXA, Dfd_Cell, Dr_SOLEXA, Ap_Cell, Ro_Cell, CG4136_SOLEXA, CG33980_SOLEXA, Hbn_SOLEXA, Lbl_Cell, Otp_Cell, Rx_Cell, CG32532_SOLEXA, NK7.1_SOLEXA, Dr_Cell, Odsh_Cell, Al_SOLEXA, Antp_Cell, Hgtx_SOLEXA, Ftz_SOLEXA, Lab_SOLEXA, Dfd_FlyReg, Ap_SOLEXA, Awh_SOLEXA, CG11294_SOLEXA, CG4136_Cell, E5_SOLEXA, Ro_SOLEXA, PhdP_SOLEXA, CG12361_SOLEXA_2, Ind_Cell, Scr_Cell, CG9876_Cell, CG18599_Cell, CG9876_SOLEXA, Otp_SOLEXA, Lbl_SOLEXA, Ubx_Cell, Ubx_SOLEXA, en_SOLEXA_2, Pph13_SOLEXA, Rx_SOLEXA, CG15696_SOLEXA, CG18599_SOLEXA, Ems_SOLEXA, Repo_Cell, Dll_Cell, C15_Cell, CG12361_SOLEXA, Abd-A_FlyReg, Repo_SOLEXA, Zen_Cell, Inv_Cell, En_SOLEXA, Lim3_Cell, Lim1_SOLEXA, CG15696_Cell, Crc_CG6272_SANGER_5, Lab_Cell, CG32105_SOLEXA, Bap_SOLEXA, CG9437_SANGER_5, AbdA_Cell, pho_FlyReg, CG33980_Cell, Cad_SOLEXA, CG4328_SOLEXA, CG4328_Cell, Gsc_Cell, vri_SANGER_5, AbdB_SOLEXA, Xrp1_CG6272_SANGER_5, Al_Cell, Exex_Cell, br-Z4_FlyReg, CG11294_Cell, Aef1_FlyReg, CG7745_SANGER_5, PhdP_Cell, Awh_Cell, prd, tup, lms, CG11085, B-H2, lms, tup, tup, bsh, exex, OdsH, unc-4, Ubx, unc-4, E5, inv, B-H2, zen, CG33980, B-H1, CG33980, HGTX, NK7.1, slou, lms, zen2, abd-A, Antp, btn, Dfd, eve, ftz, Hmx, Hmx, CG34031, zen2, en, pb, slou, unpg, inv, ovo, Lim1, C15, ems, btn, unpg, pb, bsh, Scr, zen2, CG34031, eve, Pph13, B-H1, CG11085, CG32532, en, Dll, Dfd, Dr, ap, ro, CG4136, CG33980, hbn, lbl, otp, Rx, CG32532, NK7.1, Dr, OdsH, al, Antp, HGTX, ftz, lab, Dfd, ap, Awh, CG11294, CG4136, E5, ro, PHDP, CG12361, ind, Scr, CG9876, CG18599, CG9876, otp, lbl, Ubx, Ubx, en, Pph13, Rx, CG15696, CG18599, ems, repo, Dll, C15, CG12361, abd-A, repo, zen, inv, en, Lim3, Lim1, CG15696, crc, lab, CG32105, bap, CG9437, abd-A, pho, CG33980, cad, CG4328, CG4328, Gsc, vri, Abd-B, Xrp1, al, exex, br, CG11294, Aef1, CG7745, PHDP, Awh, <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>, <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>, <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>, <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>, <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>, <S4 class 'universalmotif' [package "universalmotif"] with 20 slots>, <S4 class 'universalmotif' [package 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#>
#> [Hidden empty columns: family, organism, nsites, bkgsites, pval, qval,
#> eval.]
runTomTom()
will add its results as columns to a runDreme()
results
data.frame.
full_results <- dreme_results %>%
runTomTom()
AME is used to test for enrichment of known motifs in target sequences.
runAme()
will use the MEME_DB
entry in .Renviron
or
options(meme_db = "path/to/database.meme")
as the motif database.
Alternately, it will accept all valid inputs similar to runTomTom()
.
# here I set the evalue_report_threshold = 30 to detect motifs in the limited example sequences
# In a real analysis, evalue_report_threshold should be carefully selected
ame_results <- runAme(sequences, control = "shuffle", evalue_report_threshold = 30)
ame_results
#> # A tibble: 2 x 17
#> rank motif_db motif_id motif_alt_id consensus pvalue adj.pvalue evalue tests
#> <int> <chr> <chr> <chr> <chr> <dbl> <dbl> <dbl> <int>
#> 1 1 /usr/lo… Eip93F_… Eip93F ACWSCCRA… 5.14e-4 0.0339 18.8 67
#> 2 2 /usr/lo… Cf2-PB_… Cf2 CSSHNKDT… 1.57e-3 0.0415 23.1 27
#> # … with 8 more variables: fasta_max <dbl>, pos <int>, neg <int>,
#> # pwm_min <dbl>, tp <int>, tp_percent <dbl>, fp <int>, fp_percent <dbl>
view_tomtom_hits
allows comparing the input motifs to the top hits
from TomTom. Manual inspection of these matches is important, as
sometimes the top match is not always the correct assignment. Altering
top_n
allows you to show additional matches in descending order of
their rank.
full_results %>%
view_tomtom_hits(top_n = 1)
#> $m01_AGAGC
It can be useful to view the results from runAme()
as a heatmap.
plot_ame_heatmap()
can create complex visualizations for analysis of
enrichment between different region types (see vignettes for details).
Here is a simple example heatmap.
ame_results %>%
plot_ame_heatmap()
The FIMO tool is used to identify matches to known motifs. runFimo
will return these hits as a GRanges
object containing the genomic
coordinates of the motif match.
# Query MotifDb for a motif
e93_motif <- MotifDb::query(MotifDb::MotifDb, "Eip93F") %>%
universalmotif::convert_motifs()
#> See system.file("LICENSE", package="MotifDb") for use restrictions.
# Scan for the E93 motif within given sequences
fimo_results <- runFimo(sequences, e93_motif, thresh = 1e-3)
# Visualize the sequences matching the E93 motif
plot_sequence_heatmap(fimo_results$matched_sequence)
memes also supports importing results generated using the MEME suite outside of R (for example, running jobs on meme-suite.org, or running on the commandline). This enables use of preexisting MEME suite results with downstream memes functions.
| MEME Tool | Function Name | File Type |
|:---------:|:-------------------:|:----------:|
| Streme | importStremeXML()
| streme.xml |
| Dreme | importDremeXML()
| dreme.xml |
| TomTom | importTomTomXML()
| tomtom.xml |
| AME | importAme()
| ame.tsv* |
| FIMO | importFimo()
| fimo.tsv |
| Meme | importMeme()
| meme.txt |
* importAME()
can also use the “sequences.tsv” output when AME used
method = "fisher"
, this is optional.
The MEME Suite does not currently support Windows, although it can be installed under Cygwin or the Windows Linux Subsytem (WSL). Please note that if MEME is installed on Cygwin or WSL, you must also run R inside Cygwin or WSL to use memes.
An alternative solution is to use
Docker to run a virtual
environment with the MEME Suite installed. We provide a memes docker
container
that ships with the MEME Suite, R studio, and all memes
dependencies
pre-installed.
memes is a wrapper for a select few tools from the MEME Suite, which were developed by another group. In addition to citing memes, please cite the MEME Suite tools corresponding to the tools you use.
If you use runDreme()
in your analysis, please cite:
Timothy L. Bailey, “DREME: Motif discovery in transcription factor ChIP-seq data”, Bioinformatics, 27(12):1653-1659, 2011. full text
If you use runTomTom()
in your analysis, please cite:
Shobhit Gupta, JA Stamatoyannopolous, Timothy Bailey and William Stafford Noble, “Quantifying similarity between motifs”, Genome Biology, 8(2):R24, 2007. full text
If you use runAme()
in your analysis, please cite:
Robert McLeay and Timothy L. Bailey, “Motif Enrichment Analysis: A unified framework and method evaluation”, BMC Bioinformatics, 11:165, 2010, . full text
If you use runFimo()
in your analysis, please cite:
Charles E. Grant, Timothy L. Bailey, and William Stafford Noble, “FIMO: Scanning for occurrences of a given motif”, Bioinformatics, 27(7):1017-1018, 2011. full text
The MEME Suite is free for non-profit use, but for-profit users should purchase a license. See the MEME Suite Copyright Page for details.
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