1. FLiPS
Functional Linkage Prediction Service

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

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

4. 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

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

6. 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

7. 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

8. 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.

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

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

11. 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.

12. Functional Linkage Prediction System

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

14. Ex) Protein Complex Result of FLiPS
Proc Natl Acad Sci U S A 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.

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

16. Ex) Annotation of Hypothetical Protein

17. Ex) Annotation of Hypothetical Protein