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Infernal - sequence analysis using profiles of RNA sequence and secondary structure consensus


Align sequences to a covariance model

Construct covariance model(s) from structurally annotated RNA multiple sequence alignment(s)

Fit exponential tails for covariance model E-value determination

Convert Infernal covariance model files

Sample sequences from a covariance model

Retrieve covariance model(s) from a file

Prepare a covariance model database for cmscan

Search sequence(s) against a covariance model database

Search covariance model(s) against a sequence database

summary statistics for a covariance model file


Infernal is a suite of several programs for structural RNA sequence alignment and database homology search. It uses probabilistic models called "covariance models" (CMs) to represent the likely evolutionary homologs of a multiple alignment (or single sequence) of a structural RNA sequence family.

Along with the Rfam database of RNA families and associated CMs (, Infernal can be used to annotate homologs of known structural RNA families in genomes.

Infernal is closely related to the HMMER software suite for sequence family analysis using profile HMMs (, but is designed specifically for structural RNA sequence families. In addition to modeling the conserved sequence of a family as profile HMMs do, CMs model the family's conserved, well-nested (non-pseudoknotted) secondary structure as well. Consequently, CM search and alignment methods are relatively computationally expensive. Infernal uses profile HMMs as filters and for deriving constraints to make the CM methods more practical.

Infernal is used in three main modes: to search a sequence database for new homologs of an RNA family (or annotate homologs in a genome); to search a CM database (like Rfam) to find what known family a query sequence belongs to; and to automatically construct large multiple alignments (i.e. with an effectively unlimited number of sequences) using a CM representative of a sequence family.

Suppose you have a structurally annotated multiple sequence alignment of a RNA sequence family of interest, and you want to search a sequence database for additional homologs. The cmbuild program builds covariance model(s) from multiple alignment(s) and cmcalibrate determines important parameters for estimating the statistical significance of database hits to the model in subsequent searches.

The cmsearch program searches CM(s) against a sequence database.

Suppose you have sequence(s) that you want to analyze using a Infernal-based CM database like Rfam ( The cmpress program formats a covariance model (such as the file you would download from Rfam) into a Infernal binary database. The cmscan program searches sequence(s) against that database.

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

Infernal also includes some auxiliary tools for working with large CM databases. cmfetch fetches one or more CMs from a database. cmstat prints summary statistics about a CM file.

For compatibility with previous versions of Infernal, as well as with HMMER, the cmconvert program converts CM files to a few other formats.

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

Each program has its own man page.


This is a summary man page for the entire Infernal package. See individual man pages [cmbuild(1), for example] for usage, options, and description of each program in the package.

For complete documentation, see the user guide that came with your Infernal distribution (Userguide.pdf); or see the Infernal web page (


Copyright (C) 2023 Howard Hughes Medical Institute.
Freely distributed under the BSD open source license.

For additional information on copyright and licensing, see the file called COPYRIGHT in your Infernal source distribution, or see the Infernal web page (

Sep 2023 Infernal 1.1.5