pftools

pftools provides profile-based sequence analysis for detecting and characterizing protein motifs and searching protein sequence databases.

Key Features:

• Generalized Profiles: Uses generalized profiles derived from multiple sequence alignments that encode position-specific scores and gap penalties to describe protein motifs.
• Enhanced Sensitivity and Selectivity: Incorporates sequence weighting by inter-sequence distances (Sibbald PR, Argos P, 1990) applied automatically and employs the BLOSUM45 amino acid substitution table (Henikoff S, Henikoff JG, 1992) to improve discrimination relative to Dayhoff matrices.
• Optimized Search Capabilities: Includes an optimized implementation of the PROSITE search tool, pfsearchV3, using a heuristic that reduces search time and yields approximately two orders of magnitude speed improvement on modern x86_64 hyper-threaded quad-core desktop computers when scanning protein sequence databases for matches.

Scientific Applications:

• Distant relationship detection: Detects distant relationships between amino acid sequences using profile-based similarity.
• Protein domain detection: Identifies protein domains and motif instances in sequence datasets.
• Functional annotation: Supports functional annotation of proteins by matching sequences to profile-defined motifs.
• Genome and metagenome annotation: Enables large-scale annotation of genomes and metagenomes by rapidly scanning sequence databases for profile matches.
• Evolutionary studies: Facilitates evolutionary analysis by revealing conserved motifs and distant homologs.
• Novel protein identification: Aids identification of putative novel proteins by distinguishing true members from false positives with enhanced sensitivity.

Methodology:

Derives generalized profiles from multiple sequence alignments with position-specific scores and gap penalties, applies sequence weights based on distances (Sibbald PR, Argos P, 1990), uses the BLOSUM45 substitution matrix (Henikoff S, Henikoff JG, 1992), and performs accelerated database searches via an optimized pfsearchV3 implementation with a heuristic.