MEME Suite

MEME Suite discovers and analyzes sequence motifs in DNA and protein sequences to identify conserved regulatory and functional elements.

Key Features:

• MEME (motif discovery): Uses expectation maximization to fit a two-component finite mixture model to unaligned sequences and discovers motifs by probabilistically erasing occurrences and repeating the search.
• GLAM2 (gapped motif discovery): Identifies motifs that contain insertions and deletions, enabling discovery of motifs with gaps.
• HMM modeling: Constructs Hidden Markov Models from motif models generated via the EM algorithm to model conserved regions within sequence families.
• Sequence scanning/search: Provides MAST, FIMO, and GLAM2SCAN to scan DNA and protein databases for motif occurrences, with MAST using MEME output and furnishing statistical measures for hits.
• Motif comparison: TOMTOM compares discovered motifs to motifs in existing motif databases.
• Functional association: GOMO associates motifs with Gene Ontology (GO) terms to infer potential functions.
• Output visualization: Produces sequence LOGOs for each discovered motif to visualize motif information content and positions.

Scientific Applications:

• Transcription Factor Binding Sites: Discovery of novel transcription factor binding sites in DNA sequences to study gene regulation.
• Protein Domains: Identification of conserved protein interaction domains and motifs relevant to protein function and interactions.
• Structural Analysis: Mapping motifs onto structural elements such as alpha-helices and beta-strands, exemplified by analyses of the short-chain alcohol dehydrogenase superfamily.

Methodology:

Expectation maximization fitting of a two-component finite mixture model to unaligned sequences with iterative probabilistic masking of motif occurrences; GLAM2 for gapped motif alignment; construction of HMMs from EM-derived motif models; database searches using MAST, FIMO, and GLAM2SCAN; motif comparison via TOMTOM and GO association via GOMO; generation of sequence LOGOs.