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MEME Suite: Motif Discovery, Enrichment and Scanning Tools Explained

MEME Suite explained: which tool discovers, tests, scans or compares sequence motifs, with a task-to-tool table and input requirements.

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The MEME Suite is a collection of software tools for finding, testing, scanning for and comparing sequence motifs in DNA, RNA or protein sequences. Its own documentation groups the tools by task: motif discovery, motif enrichment, motif searching (scanning) and motif comparison. This guide adds a task-to-tool decision table so you can pick the right program for your question. Information below is drawn from the MEME Suite overview documentation and the project’s Nucleic Acids Research papers, read 2026-11-08.

Short answer

Use MEME or STREME to discover new motifs in a set of sequences, SEA, AME or CentriMo to test whether motifs you already know are enriched, FIMO to find where a motif occurs, and Tomtom to compare a motif with known motifs. Not every tool is offered as a web service, so some work requires a local installation.

Definition and scope

A sequence motif is a recurring pattern in biological sequences, for example a transcription factor binding pattern in DNA. The MEME Suite was introduced in 2009 as MEME SUITE: tools for motif discovery and searching and described again in Bailey TL, Johnson J, Grant CE, Noble WS, “The MEME Suite”, Nucleic Acids Research 2015;43(Web Server issue):W39-W49, doi:10.1093/nar/gkv416. The 2015 paper describes a web-based collection of 13 tools, six of them added since 2009 (DREME, MEME-ChIP, CentriMo, AME, SpaMo and MCAST), freely available for academic use, with source code for local installation. The project lists NIH grant R01 GM103544 as support. The tool list changes between releases; DREME, for instance, is now marked deprecated in the current overview.

How it is used in practice

A typical analysis moves through the categories in the overview documentation:

  1. Discover motifs in a set of unaligned DNA, RNA or protein sequences.
  2. Test enrichment of discovered or known motifs against shuffled or control sequences.
  3. Scan sequences for individual occurrences of a motif.
  4. Compare a motif against databases of known motifs. Motif databases such as the one described in the JASPAR transcription factor binding profile guide are the usual reference sets for this step.

The documentation also lists utilities (BED2FASTA, AMA), motif format converters and FASTA utilities. The overview states: “Not all the tools are available as webservices, so to get the full power of the MEME Suite you will need to download and install a local copy.”

Which MEME Suite tool do I need?

Question Tool What the documentation says it does
Discover ungapped motifs in a set of unaligned sequences MEME Probabilistic model of ungapped motifs in unaligned DNA, RNA or protein sequences
Discover ungapped motifs in a large set STREME Finds motifs enriched relative to shuffled or control sequences; DNA, RNA, protein or a custom alphabet
Comprehensive motif analysis, motif anywhere in the sequence XSTREME Comprehensive analysis for motifs that can appear anywhere
Comprehensive analysis, motif near the centre (e.g. ChIP-seq peaks) MEME-ChIP Comprehensive analysis where motifs tend to be central
Motifs with gaps GLAM2 Gapped motifs in DNA or protein
Post-translational modification motifs MoMo PTM motifs in fixed-width protein sequences
Are my known motifs enriched? SEA Known motifs enriched relative to shuffled or control sequences
Is a motif enriched at a particular position? CentriMo Local enrichment; requires equal-length sequences
Enrichment of known motifs, or of low scores you specify AME Tests known motifs for enrichment
Preferred spacing between motifs SpaMo Preferred spacing relative to a primary motif (DNA)
Possible biological roles GOMo Possible Gene Ontology roles for DNA-binding motifs
Where does a motif occur? FIMO Reports occurrences scoring below a p-value threshold
Score sequences against several motifs MAST Combines p-values; assumes one occurrence per motif per sequence
Clusters of known motifs MCAST Finds clusters of known motifs in any order
Conserved matches across species MOTIPH Needs aligned sequences and a maximum-likelihood phylogenetic tree
Is my motif already known? Tomtom Finds known motifs similar to a given DNA or RNA motif
Which gene might a region regulate? T-Gene Predicts regulatory links between chromosomal regions and genes

Gene-level follow-up often continues in resources such as the NCBI Gene database or the DAVID bioinformatics resource.

Where it matters for lab work

Check input requirements before you run

  • CentriMo expects equal-length sequences.
  • MOTIPH needs aligned sequences and a maximum-likelihood phylogenetic tree.
  • MoMo expects fixed-width protein sequences.
  • MAST assumes one occurrence of each motif per sequence.

Web server versus local install

The documentation says not all tools are offered as web services. If a method in a paper depends on a tool you cannot find on the server, plan for a local installation, and record the release you used, because the tool set varies by release.

Choosing between near neighbours

  • XSTREME versus MEME-ChIP: the difference the documentation draws is where motifs are expected: anywhere, or tending to be central.
  • MAST, FIMO and MCAST: FIMO reports individual occurrences below a p-value threshold, MAST scores whole sequences, and MCAST looks for clusters of known motifs in any order.

Common misunderstandings

  • Scanning is not discovery. FIMO and MAST look for motifs you already have; MEME, STREME and GLAM2 find new ones.
  • Enrichment is relative. SEA and STREME test enrichment against shuffled or control sequences, so the choice of control matters to the result.
  • A deprecated tool still appears in older papers. DREME is deprecated in the current documentation; STREME is the listed tool for motifs in large sets.
  • Motif discovery does not prove binding. A motif is a statistical pattern in sequences, not experimental confirmation of binding.

Frequently asked questions

What is the MEME Suite used for?

Discovering, enriching, scanning for and comparing sequence motifs in DNA, RNA and protein sequences.

Is the MEME Suite free?

The 2015 paper describes it as freely available for academic use, with source code for local installation. Check the project site for the terms that apply to your use.

What is the difference between MEME and STREME?

Both find ungapped motifs. The documentation presents STREME for large sequence sets, finding motifs enriched relative to shuffled or control sequences.

Which tool compares my motif with known motifs?

Tomtom, for DNA or RNA motifs.

Sources

  • MEME Suite documentation overview, meme-suite.org/meme/doc/overview.html, read 2026-11-08.
  • Bailey TL, Johnson J, Grant CE, Noble WS. The MEME Suite. Nucleic Acids Res 2015;43(W1):W39-W49. PMC4489269, read 2026-11-08.
  • Bailey TL et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 2009 (PMID 19458158).

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