Infernal 1.1: 100-fold faster RNA homology searches

Abstract

Summary: Infernal builds probabilistic profiles of the sequence and secondary structure of an RNA family called covariance models (CMs) from structurally annotated multiple sequence alignments given as input. Infernal uses CMs to search for new family members in sequence databases and to create potentially large multiple sequence alignments. Version 1.1 of Infernal introduces a new filter pipeline for RNA homology search based on accelerated profile hidden Markov model (HMM) methods and HMM-banded CM alignment methods. This enables ∼100-fold acceleration over the previous version and ∼10 000-fold acceleration over exhaustive non-filtered CM searches.

Availability: Source code, documentation and the benchmark are downloadable from http://infernal.janelia.org. Infernal is freely licensed under the GNU GPLv3 and should be portable to any POSIX-compliant operating system, including Linux and Mac OS/X. Documentation includes a user's guide with a tutorial, a discussion of file formats and user options and additional details on methods implemented in the software.

Contact: nawrockie@janelia.hhmi.org

Fig. 1.

ROC-like curves for the benchmark. Plots are shown for the new Infernal 1.1 with and without filters, for the old Infernal 1.0.2, for profile HMM searches with nhmmer (from the HMMER package included in Infernal 1.1, default parameters) and for family-pairwise-searches with BLASTN (ncbi-blast-2.2.28+, default parameters). The maximum sensitivity (not shown) for default Infernal 1.1 is 0.81 (629 of 820 true positives found), which is achieved at a false-positive rate of 0.19/Mb/query. For non-filtered Infernal, maximum sensitivity is 0.87 at 2.9 false positives per Mb per query. This indicates that at high false-positive rates the filters prevent some true positives from being found, but prevent many more false positives from being found. CPU times are total times for all 106 family searches measured for single execution threads on 3.0 GHz Intel Xeon processors. The Infernal times do not include time required for model calibration.