Functional Equivalency Inferred from “Authoritative Sources” in Networks of Homologous Proteins

A one-on-one mapping of protein functionality across different species is a critical component of comparative analysis. This paper presents a heuristic algorithm for discovering the Most Likely Functional Counterparts (MoLFunCs) of a protein, based on simple concepts from network theory. A key feature of our algorithm is utilization of the user's knowledge to assign high confidence to selected functional identification. We show use of the algorithm to retrieve functional equivalents for 7 membrane proteins, from an exploration of almost 40 genomes form multiple online resources. We verify the functional equivalency of our dataset through a series of tests that include sequence, structure and function comparisons. Comparison is made to the OMA methodology, which also identifies one-on-one mapping between proteins from different species. Based on that comparison, we believe that incorporation of user's knowledge as a key aspect of the technique adds value to purely statistical formal methods.

• Publication year

  2009

• Venue

  PLoS ONE

• Publication date

  2009-06-12

• Fields of study

  Biology, Medicine, Computer Science

• Identifiers
  DOI 10.1371/journal.pone.0005898PMID 19521530PMCID 2690840
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Transporter Classification Database: recent advances

  2008cited by this paper
• The Genomes On Line Database (GOLD) in 2007: status of genomic and metagenomic projects and their associated metadata

  2008cited by this paper
• Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH.

  2008cited by this paper
• Choosing BLAST options for better detection of orthologs as reciprocal best hits

  2008cited by this paper
• A critical GxxxA motif in the γ6 calcium channel subunit mediates its inhibitory effect on Cav3.1 calcium current

  2008cited by this paper
• Ensembl 2008

  2007cited by this paper
• Evolution and structural diversification of hyperpolarization-activated cyclic nucleotide-gated channel genes.

  2007cited by this paper
• Assessing Performance of Orthology Detection Strategies Applied to Eukaryotic Genomes

  2007cited by this paper
• OMA Browser - Exploring orthologous relations across 352 complete genomes

  2007cited by this paper
• The Genomes On Line Database (GOLD) in 2007: status of genomic and metagenomic projects and their associated metadata

  2007cited by this paper
• eggNOG: automated construction and annotation of orthologous groups of genes

  2007cited by this paper
• Uncoupling Proton Activation of Vanilloid Receptor TRPV1

  2007cited by this paper
• Voltage-Gated Potassium Channels: Regulation by Accessory Subunits

  2006cited by this paper
• Pigment Pattern in jaguar/obelix Zebrafish Is Caused by a Kir7.1 Mutation: Implications for the Regulation of Melanosome Movement

  2006cited by this paper
• Automatic clustering of orthologs and inparalogs shared by multiple proteomes

  2006cited by this paper
• An Arginine Residue in the Pore Region Is a Key Determinant of Chloride Dependence in Cardiac Pacemaker Channels*

  2005cited by this paper
• Pore-to-gate coupling of HCN channels revealed by a pore variant that contributes to gating but not permeation.

  2005cited by this paper
• Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel

  2005cited by this paper
• Functional characterisation of the S512Y mutant vanilloid human TRPV1 receptor

  2005cited by this paper
• Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels

  2004cited by this paper
• Structure and gating of the glutamate receptor ion channel.

  2004cited by this paper
• MUSCLE: multiple sequence alignment with high accuracy and high throughput.

  2004influential reference
• NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins

  2004cited by this paper
• Molecular Basis of Ion Selectivity, Block, and Rectification of the Inward Rectifier Kir3.1/Kir3.4 K+ Channel

  2003cited by this paper
• A common architecture for K+ channels and ionotropic glutamate receptors?

  2003cited by this paper
• OrthoMCL: identification of ortholog groups for eukaryotic genomes.

  2003cited by this paper
• Sequence-function analysis of the K+-selective family of ion channels using a comprehensive alignment and the KcsA channel structure.

  2003cited by this paper
• Cross-referencing eukaryotic genomes: TIGR Orthologous Gene Alignments (TOGA).

  2002cited by this paper
• Potassium channel ontogeny.

  2002cited by this paper
• Orthology, paralogy and proposed classification for paralog subtypes.

  2002influential reference
• Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.

  2001cited by this paper
• Glutamate receptor channel signatures.

  2001cited by this paper
• Cyclic nucleotide-gated channels: shedding light on the opening of a channel pore

  2001cited by this paper
• The S4–S5 linker couples voltage sensing and activation of pacemaker channels

  2001cited by this paper
• Co-evolution of proteins with their interaction partners.

  2000cited by this paper
• Effects of mutation at a conserved N‐glycosylation site in the bovine retinal cyclic nucleotide‐gated ion channel

  2000cited by this paper
• Stable cation coordination at a single outer pore residue defines permeation properties in Kir channels

  2000cited by this paper
• Molecular determinants of a Ca2+‐binding site in the pore of cyclic nucleotide‐gated channels: S5/S6 segments control affinity of intrapore glutamates

  1999cited by this paper
• Authoritative sources in a hyperlinked environment

  1999influential reference
• Profile hidden Markov models

  1998cited by this paper
• Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

  1997cited by this paper
• A genomic perspective on protein families.

  1997cited by this paper
• CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.

  1994influential reference
• Identification of an external divalent cation-binding site in the pore of a cGMP-activated channel.

  1993cited by this paper
• Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence

  1991cited by this paper
• Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila.

  1988cited by this paper
• Bioinformatics Original Paper Coco-cl: Hierarchical Clustering of Homology Relations Based on Evolutionary Correlations

  year unknowncited by this paper

• Comprehensively Surveying Structure and Function of RING Domains from Drosophila melanogaster

  2011cites this paper
• Understanding the “Horizontal Dimension” of Molecular Evolution to Annotate, Classify, and Discover Proteins with Functional Domains

  2010cites this paper
• Evolutionary coupling in the KV1.2-β2 complex

  2010cites this paper