Searching for patterns, motifs, or profiles in a DNA or protein sequence

This is a traditional bioinformatics task, and many tools do this in a variety of ways. One main determinant of tool is the representation of what you're looking for. ​Identifying enriched sites is a related but different task.

Search with a pattern (text, with optional choices at some positions)

​dreg (EMBOSS suite) - for nucleic acids (where "pattern" is a regular expression)

dreg -pattern "GGCC[ACGT]" -sequence My_promoters.fa -outfile My_promoters.GGCCN.dreg_out.txt

​preg (EMBOSS suite) - for proteins (where "pattern" is a regular expression)

dreg -pattern "LPE[ACS]G" -sequence My_proteins.fa -outfile My_proteins.fa.LPEMG.preg_out.txt

​fuzznuc (EMBOSS suite) - for nucleic acids (where "pmismatch" is the number of mismatches in the pattern)

fuzznuc -pattern "nnnGGCCTnnn" -sequence My_promoters.fa -pmismatch 1 -outfile My_promoters.GGCCT.1mis.fuzznuc_out.txt

​fuzzpro (EMBOSS suite) - for proteins (where "pmismatch" is the number of mismatches in the pattern)

fuzzpro -pattern "xxxxLPEAGxxxx" -sequence My_proteins.fa -pmismatch 1 -outfile My_proteins.LPEAG.1mis.fuzzpro_out.txt

EMBOSS output format can be changed with the option, -rformat. See ​EMBOSS Report Formats for more details.

Search with a custom profile (a probability matrix, with choices at all positions)

These searches are generally a two-step process, one step to create the motif and one step to search with it. There are several choices of detailed options, so check out the documentation. You need to ​align your sequences before you can create a profile.

​prophecy + ​profit (EMBOSS suite) - for proteins

prophecy -sequence Aligned_protein_sites.fa -type F -name MyProfile -outfile MyProfile.txt -filter
profit -infile MyProfile.txt -sequence My_proteins.fa -outfile My_proteins.MyProfileprofit_out.txt

​HMMER - for proteins or nucleic acids

# Create a HMM from a set of proteins or nucleic acids (fasta or other common format)
hmmbuild MyProfile.hmm Aligned_protein_sites.fa
# Use the HMM to search a fasta file of proteins
hmmsearch MyProfile.hmm Protein_set.fa > Protein_set.MyProfile.hmmsearch_out.txt

​JASPAR - for transcription factor binding sites

​MEME Suite For proteins or nucleic acids

• Build a PWM from a series of sequences using the ​meme command

  meme Sequence_set.fa -protein -nmotifs 5 -minw 8 -maxw 12 -o output_directory
  

Program options:

-protein: specifies your input sequences are amino acids.
-dna: specifies your input sequences are DNA nucleotides.
-nmotifs: indicates the number of motifs to look for in your sequences
-minw, -maxw: minimum and maximum motif widths

• Using the ​MAST program within the MEME-suite, with the PWM output by the above command you can search a list of protein sequences, in FASTA format, for your motif.

  mast -minseqs 100 -m 1 -comp -ev 10 -o output_directory
  

Program options:

-minseqs: Specifies the number of sequences to analyze.
-m: Specifies the number of motifs within your matrix file.
-comp: This option can improve search selectivity when erroneous matches are due to biased sequence composition.
-ev: MAST only displays sequences matching your query with E-values below the given threshold you specify here. By default, sequences in the database with matches with E-values less than 10 are displayed. If your motifs are very short or have low information content (are not very specific), it may be impossible for any sequence to achieve a low E-value.

Search with a dataset of profiles

​JASPAR - for transcription factor binding sites

• Select a JASPAR CORE database (like ​Vertebrata) to search your DNA sequence(s) with the set of profiles

​TRANSFAC's match - for transcription factor binding sites

• commercial application requiring a license for the most up-to-date version
• Whitehead only: See BaRC_datasets/Transfac for the command-line program and data files

  # Search using all Transfac profiles
  match matrix.dat MyPromoters.fa MyPromoters.match_out.txt minSUM_good.prf
  # Search using a subset of profiles
  match matrix.dat MyPromoters.fa MyPromoters.vert.match_out.txt vertebrate_non_redundant_minSUM.prf
  

• Publication: ​Kel et al., 2003
• Public web site (older data): ​http://www.gene-regulation.com/cgi-bin/pub/programs/match/bin/match.cgi

​HMMER - for proteins or nucleic acids

• Use a set of HMMs (like Pfam or another public protein domain resource) to search a fasta file of proteins

  hmmsearch Pfam-A.hmm MyProteins.fa > MyProteins.Pfam-A.hmm.out.txt
  

​Bioconductor packages

• ​TFBSTools