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


Align sequences to a covariance model

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

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
(http://rfam.sanger.ac.uk), 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 (http://hmmer.org), 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 (http://rfam.sanger.ac.uk). 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

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.

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