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HMMER - profile HMMs for biological sequence analysis


Align sequences to a profile

Construct profile(s) from multiple sequence alignment(s)

Convert profile file to various HMMER and non-HMMER formats

Sample sequences from a profile

Retrieve profile HMM(s) from a file

Daemon used for hmmer.org web server, for phmmer-, hmmsearch-, and hmmscan-like search

Prepare an HMM database for hmmscan

Search protein sequence(s) against a protein profile database

Search protein profile(s) against a protein sequence database

Collect profile score distributions on random sequences

Summary statistics for a profile file

Iterative search of a protein sequence against a protein sequence database

Search nucleotide sequence(s), alignment(s), or profile(s) against a nucleotide sequence

Search nucleotide sequence(s) against a nucleotide profile database

Search a protein sequence(s) against a protein sequence database


HMMER is a suite of several programs for biological sequence alignment and database
homology search. It uses probabilistic models called "profile hidden Markov models"
(profile HMMs) to represent the likely evolutionary homologs of a single sequence or a
multiple alignment of a sequence family. A main avenue of research is to improve the
evolutionary predictive models in HMMER to be able to recognize and accurately align
increasingly remote homologs, distant in time.

HMMER is also used as an organizational tool, to group the exponentially growing number of
biological sequences into a vastly smaller set of well-annotated sequence families. New
sequences can be annotated by comparison against curated sequence family databases of
prebuilt HMMER profiles, in addition or instead of comparison to the entire sequence
database. Databases such as Pfam, SMART, and TIGRfams, among others, are based on this

HMMER is used in three main modes: to search a sequence database for new homologs of a
sequence or a sequence family; to search a profile database (like Pfam) to find what known
family a query sequence belongs to, or what domains it has; and to automatically construct
large multiple alignments (i.e. with an effectively unlimited number of sequences) using a
profile representative of a sequence family.

Suppose you have a multiple sequence alignment of a sequence family of interest, and you
want to search a sequence database for additional homologs. The hmmbuild program builds
profile(s) from multiple alignment(s). The hmmsearch program searches protein profile(s)
against a protein sequence database, and nhmmer searches nucleotide profile(s) against a
nucleotide sequence database.

Suppose you have a single sequence of interest, and you want to search a sequence database
for additional homologs. The phmmer program searches a single protein sequence against a
protein sequence database. The jackhmmer program does the same thing but iteratively --
homologs detected in a previous round are incorporated into a new profile, and the new
profile is searched again. phmmer is used like BLASTP, and jackhmmer is used like a
protein PSI-BLAST. The nhmmer program searches a single nucleotide sequence against a
nucleotide sequence.

Suppose you have sequence(s) that you want to analyze using a HMMER-based profile HMM
database like Pfam (http://pfam.sanger.ac.uk). The hmmpress program formats a profile HMM
flatfile (such as the file you would download from Pfam) into a HMMER binary database.
The hmmscan program searches protein sequence(s) against that database. The nhmmscan
program can similarly search nucleotide sequence(s) against a pressed database of
nucleotide profiles, such as from Dfam (http://dfam.janelia.org).

Suppose you want to align lots of sequences. You can construct a manageably small
alignment of a representative set of sequences, build a profile with hmmbuild, and use the
hmmalign program to align any number of sequences to that profile.

HMMER also includes some auxiliary tools for working with large profile databases.
hmmfetch fetches one or more profiles from a database. hmmstat prints summary statistics
about a profile file.

For compatibility with other profile software and previous versions of HMMER, the
hmmconvert program converts profiles to a few other formats. We intend to add more support
for other formats over time.

The hmmemit program generates (simulates) "homologous" sequences by sampling from a
profile. It can also generate a "consensus" sequence.

The hmmsim program is a simulator used for collecting statistics about score distributions
on random sequences.

Each program has its own man page.

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