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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| HMMER | 2/2 | https://en.wikipedia.org/wiki/HMMER | reference | science, encyclopedia | 2026-05-05T10:11:50.267033+00:00 | kb-cron |
=== Improvements in speed === A major aim of the HMMER3 project, started in 2004 was to improve the speed of HMMER searches. While profile HMM-based homology searches were more accurate than BLAST-based approaches, their slower speed limited their applicability. The main performance gain is due to a heuristic filter that finds high-scoring un-gapped matches within database sequences to a query profile. This heuristic results in a computation time comparable to BLAST with little impact on accuracy. Further gains in performance are due to a log-likelihood model that requires no calibration for estimating E-values, and allows the more accurate forward scores to be used for computing the significance of a homologous sequence. HMMER still lags behind BLAST in speed of DNA-based searches; however, DNA-based searches can be tuned such that an improvement in speed comes at the expense of accuracy.
=== Improvements in remote homology searching === The major advance in speed was made possible by the development of an approach for calculating the significance of results integrated over a range of possible alignments. In discovering remote homologs, alignments between query and hit proteins are often very uncertain. While most sequence alignment tools calculate match scores using only the best scoring alignment, HMMER3 calculates match scores by integrating across all possible alignments, to account for uncertainty in which alignment is best. HMMER sequence alignments are accompanied by posterior probability annotations, indicating which portions of the alignment have been assigned high confidence and which are more uncertain.
=== DNA sequence comparison === A major improvement in HMMER3 was the inclusion of DNA/DNA comparison tools. HMMER2 only had functionality to compare protein sequences.
=== Restriction to local alignments === While HMMER2 could perform local alignment (align a complete model to a subsequence of the target) and global alignment (align a complete model to a complete target sequence), HMMER3 only performs local alignment. This restriction is due to the difficulty in calculating the significance of hits when performing local/global alignments using the new algorithm.
== See also == Hidden Markov model Sequence alignment software Pfam UGENE Several implementations of profile HMM methods and related position-specific scoring matrix methods are available. Some are listed below:
HH-suite SAM PSI-BLAST MMseqs2 PFTOOLS GENEWISE PROBE META-MEME Archived 2009-08-31 at the Wayback Machine BLOCKS GPU-HMMER DeCypherHMM
== References ==
== External links == Official website HMMER3 announcement A blog posting on HMMER policy on trademark, copyright, patents, and licensing Archived 2016-03-06 at the Wayback Machine