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 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.