FLiPS Functional Linkage Prediction Service

Functional Linkage of Proteins Protein-Protein Interaction Protein Complex Metabolic and Signaling Pathway

Prediction of Functional Linkage Genome Context Analysis (GCA) Phylogenetic Profile (PP) method Rosetta Stone (RS) method Gene Neighbor (GN) method Gene Cluster (GC) method

Phylogenetic Profile Method The Phylogenetic Profile Method uses the co-occurrence or absence of pairs of nonhomologous genes across genomes to infer functional relatedness. Phylogenetic profile

Phylogenetic Profile Method Next, we determine the probability that two proteins have coevolved; this is based on the similarity of their profiles.

Rosetta Stone Method Occasionally, two proteins expressed separately in one organism can be bound as a single chain in the same or a second genome. Analysis of gene fusion/division events to infer functional relatedness Rosetta Stone protein

Rosetta Stone Method To screen out these confounding fusion events we compute the probability that two proteins are found linked by the Rosetta Stone method by chance alone

Gene Neighbor Method Some of the operons contained within a particular organism may be conserved across other organisms. The genes within the operon are functionally coupled and are perhaps components of a protein complex or pathway.

Gene Neighbor Method We generate a P value for the likelihood that two proteins are coded within a conserved operon.

Gene Cluster Method Within bacteria, proteins of closely related function are often transcribed from a single functional unit known as an operon

Gene Cluster Method We assume that the probability that two genes that are adjacent and coded on the same strand are part of an operon is 1-P.

Functional Linkage Prediction System

Ex) Protein-Protein Interaction Figure 5 Genome Res. 2006 May;16(5):686-91 Large-scale comprehensive pull-down assay Result of FLiPS

Ex) Protein Complex Result of FLiPS Proc Natl Acad Sci U S A. 1992 March 15; 89(6): 2360–2364 Result of FLiPS Maltose transport across the cytoplasmic membrane of Escherichia coli is dependent on the presence of a periplasmic maltose-binding protein (MBP), the product of the malE gene. The products of the malF, malG, and malK genes form a membrane-associated complex that catalyzes the hydrolysis of ATP to provide energy for the transport event.

Ex) Pathway b2020 b2022 b2021 b2023 b2024 b2019 b2026 Result of FLiPS

Ex) Annotation of Hypothetical Protein

Ex) Annotation of Hypothetical Protein