HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised Classification of Superfamily Protein Sequences with a reliable Cut-off Threshold

PAGNUCO IA; REVUELTA MV; BONDINO HG; BRUN M; ARJEN TEN HAVE

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018 vol. 13

1932-6203

BackgroundProtein superfamilies can be divided intosubfamilies of proteins with different functional characteristics.Their sequences can be classified hierarchically, which is part ofsequence function assignation. Typically, there are no clearsubfamily hallmarks that would allow pattern-based functionassignation by which this task is mostly achieved based on thesimilarity principle. This is hampered by the lack of a scorecut-off that is both sensitive and specific.ResultsHMMER Cut-off Threshold Tool (HMMERCTTER)adds a reliable cut-off threshold to the popular HMMER. Using a highquality superfamily phylogeny, it clusters a set of trainingsequences such that the cluster-specific HMMER profiles show clusteror subfamily member detection with 100% precision and recall (P&R),thereby generating a specific threshold as inclusion cut-off.Profiles and thresholds are then used as classifiers to screen atarget dataset. Iterative inclusion of novel sequences to groups andthe corresponding HMMER profiles results in high sensitivity whilespecificity is maintained by imposing 100% P&R self detection.In three presented case studies of protein superfamilies,classification of large datasets with 100% precision was achievedwith over 95% recall. Limits and caveats are presented andexplained.ConclusionsHMMERCTTERis a promising protein superfamily sequence classifier provided highquality training datasets are used. It provides a decision supportsystem that aids in the difficult task of sequence functionassignation in the twilight zone of sequence similarity. Allrelevant data and source codes are available from the Githubrepository at the following URL:https://github.com/BBCMdP/HMMERCTTERh2 { margin-top: 0.17in; margin-bottom: 0.17in; direction: ltr; color: rgb(0, 0, 10); text-align: left; }h2.western { font-family: "Arial", sans-serif; font-size: 16pt; }h2.cjk { font-family: "Droid Sans Fallback"; font-size: 16pt; }h2.ctl { font-size: 14pt; font-weight: normal; }h1 { margin-top: 0in; margin-bottom: 0in; direction: ltr; color: rgb(0, 0, 10); text-align: left; }h1.western { font-family: "Arial", sans-serif; font-size: 18pt; }h1.cjk { font-family: "Droid Sans Fallback"; font-size: 18pt; }h1.ctl { font-family: "DejaVu Sans"; font-size: 14pt; font-weight: normal; }p { margin-bottom: 0.08in; direction: ltr; color: rgb(0, 0, 10); text-align: left; }p.western { font-family: "Times", "Times New Roman", serif; font-size: 12pt; }p.cjk { font-family: "DejaVu Sans"; font-size: 12pt; }p.ctl { font-family: "DejaVu Sans"; font-size: 12pt; }