HMMER

HMMER

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HMMER: protein sequence similarity searches using probabilistic methods.

 

Introductory reading

Eddy (2009) A new generation of homology search tools based on probabilistic inference. Genome Inform 23:205-11. (pmid: 20180275)

[ PubMed ] Many theoretical advances have been made in applying probabilistic inference methods to improve the power of sequence homology searches, yet the BLAST suite of programs is still the workhorse for most of the field. The main reason for this is practical: BLAST's programs are about 100-fold faster than the fastest competing implementations of probabilistic inference methods. I describe recent work on the HMMER software suite for protein sequence analysis, which implements probabilistic inference using profile hidden Markov models. Our aim in HMMER3 is to achieve BLAST's speed while further improving the power of probabilistic inference based methods. HMMER3 implements a new probabilistic model of local sequence alignment and a new heuristic acceleration algorithm. Combined with efficient vector-parallel implementations on modern processors, these improvements synergize. HMMER3 uses more powerful log-odds likelihood scores (scores summed over alignment uncertainty, rather than scoring a single optimal alignment); it calculates accurate expectation values (E-values) for those scores without simulation using a generalization of Karlin/Altschul theory; it computes posterior distributions over the ensemble of possible alignments and returns posterior probabilities (confidences) in each aligned residue; and it does all this at an overall speed comparable to BLAST. The HMMER project aims to usher in a new generation of more powerful homology search tools based on probabilistic inference methods.

 

Contents

HMMs - Presentation by Joe Wu, BCB410 - 2011

 

Exercises

Exercises - by Joe Wu, BCB410 - 2011

 

Further reading and resources

Finn et al. (2011) HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 39:W29-37. (pmid: 21593126)

[ PubMed ] [ DOI ] HMMER is a software suite for protein sequence similarity searches using probabilistic methods. Previously, HMMER has mainly been available only as a computationally intensive UNIX command-line tool, restricting its use. Recent advances in the software, HMMER3, have resulted in a 100-fold speed gain relative to previous versions. It is now feasible to make efficient profile hidden Markov model (profile HMM) searches via the web. A HMMER web server (http://hmmer.janelia.org) has been designed and implemented such that most protein database searches return within a few seconds. Methods are available for searching either a single protein sequence, multiple protein sequence alignment or profile HMM against a target sequence database, and for searching a protein sequence against Pfam. The web server is designed to cater to a range of different user expertise and accepts batch uploading of multiple queries at once. All search methods are also available as RESTful web services, thereby allowing them to be readily integrated as remotely executed tasks in locally scripted workflows. We have focused on minimizing search times and the ability to rapidly display tabular results, regardless of the number of matches found, developing graphical summaries of the search results to provide quick, intuitive appraisement of them.