ProtPhylo

ProtPhylo identifies functional associations between proteins and phenotypes by analyzing phylogenetic profiles derived from over 9.7 million non-redundant protein sequences across bacteria, eukaryotes, and archaea.

Key Features:

• Extensive Database: Provides phylogenetic profiles for 2048 fully sequenced organisms—1678 bacterial species, 255 eukaryotic species, and 115 archaeal species.
• Orthology Inference Methods: Implements pair-wise sequence comparisons (Best Hits and Best Reciprocal Hits) and clustering-based methods (OrthoMCL and eggNOG) for orthology inference.
• Phylogenetic Profiling: Infers functional associations by examining co-occurrence patterns of orthology relationships across species.
• Similarity Measurement: Ranks phylogenetic neighbors using the Hamming distance metric between profiles.
• Prioritization and Filtering: Prioritizes candidate hits using subcellular localization, known protein-protein interactions, membrane-spanning regions, and protein domains.
• Data Export: Exports lists of proteins associated with queries into CSV text files.

Scientific Applications:

• Molecular basis of phenotypes: Infers candidate proteins associated with phenotypic traits by detecting co-evolutionary signals.
• Discovery of functional relationships: Identifies candidate functional relationships between proteins through shared phylogenetic profiles.
• Evolutionary conservation analysis: Analyzes conservation patterns across bacteria, eukaryotes, and archaea.
• Hypothesis generation for gene function and interaction networks: Supports generation of hypotheses about gene function and interaction networks based on co-evolution.

Methodology:

Constructs phylogenetic profiles by analyzing orthologous relationships across species; uses orthology inference methods including Best Hits, Best Reciprocal Hits, OrthoMCL, and eggNOG; ranks profile similarity with Hamming distance; identifies co-evolving proteins as candidate functional linkages; prioritizes candidates using subcellular localization, protein-protein interactions, membrane-spanning regions, and protein domains.