Physical interaction annotation-BiFC

[Hsinyugithub]

I came across this experiment using BiFC to prove the protein-protein interaction. Is it possible to add this in the interaction type? @jseager7

1.The publication:
https://www.cell.com/action/showPdf?pii=S1674-2052%2818%2930061-3

2.What are BiFC and FRET:
Bimolecular Fluorescence Complementation (BiFC) and Förster Resonance Energy Transfer (FRET) are both powerful techniques used to study protein-protein interactions in live cells, but they differ significantly in their principles, applications, and limitations.

3. The main differences between BiFC and FRET:
   BiFC:
   Involves splitting a fluorescent protein (e.g., YFP or GFP) into two non-fluorescent fragments. Each fragment is fused to a protein of interest. If the two proteins interact, the fragments come together and reconstitute the fluorescent protein, emitting fluorescence.

FRET:
Relies on energy transfer between two fluorophores: a donor and an acceptor. When the donor is excited by a specific wavelength, it can transfer energy to the acceptor only if they are within 1–10 nm, causing the acceptor to fluoresce.

[jseager7]

@Hsinyugithub It is possible to add BiFC as a new interaction type. However BiFC is not in the BioGRID Experimental Evidence Codes, which is where all the other interaction types come from. Since there are no interaction types in the list that are not also in BioGRID, I assume this list is a controlled vocabulary that PomBase doesn't want to diverge from.

Since the list of interaction types is shared between all Canto versions, I would have to copy the whole list into our own configuration file in order to add BiFC, which means any changes that PomBase makes to the list in future wouldn't be synchronised automatically with us, which isn't ideal.

The BioGRID evidence codes mention BiFC in the context of Protein-Fragment Complementation Assay (PCA) (see below), so maybe for now you could use PCA as the interaction type, and note the fact that it was a BiFC assay in the Comment field?

PCA - An interaction is inferred through the use of a Protein-Fragment Complementation Assay (PCA) in which a bait protein is expressed as a fusion to either an N- or C- terminal peptide fragment of a reporter protein and a prey protein is expressed as a fusion to the complementary C- or N- terminal fragment, respectively, of the same reporter protein. Interaction of bait and prey proteins bring together complementary fragments, which can then fold into an active reporter, e.g. the split-ubiquitin assay (e.g. PMID: 12134063, Figs. 1,2), bimolecular fluorescent complementation (BiFC). More examples of PCAs are discussed in this paper.

Copilot confirmed that BiFC is a type of PCA:

BiFC is a specific type of PCA where the reporter is a fluorescent protein (commonly GFP, YFP, or Venus). When the two non-fluorescent fragments of the fluorescent protein are brought together by the interaction of the fused proteins, they reassemble into a fluorescent complex, allowing visualization of the interaction in living cells.

[Hsinyugithub]

Thanks @jseager7. This makes sense. However, I think PCA should be spelled out as 'Protein-Fragment Complementation Assay,' since not everyone may know what PCA stands for (or maybe it's just me). :P

[jseager7]

I just discovered that the definition of 'PCA' appears if you leave your mouse hovered over the option:

This works for all the other terms.

A better solution would be to have the term definitions shown next to the dropdown, like what happens with the phenotype lookup, but I don't know how complicated that would be to implement.

The physical interaction terms are hard-coded into Canto's configuration (see here for PCA), so it would be possible to rename 'PCA' to 'Protein-Fragment Complementation Assay' in the dropdown, but we'd need support from PomBase for this, for the reasons I mentioned previously.

I'm happy to make that request if you want it. We could also consider expanding 'FRET' to 'Fluorescence Resonance Energy Transfer'.

[Hsinyugithub]

Personally, I prefer 'Protein-Fragment Complementation Assay' and 'Fluorescence Resonance Energy Transfer'. Not sure if @martin2urban feels the same.