How do you get functional/biological role of motifs?

Question

[DNAngel]

Just wondering if anyone here is familiar with motifs obtained from databases like JASPAR. It is very easy to get a list of motifs and their class/family that they belong to (which can give a vague idea of their role) but does anyone know how to also extract their functional role if given a list of motifs? Or would this just be simple google search and reading papers (I have about 2000 motifs to go through). I have also used the meme package GOMO on my enriched motifs which does help in giving me a general idea of their biological function - but I have no way to associate which specific motif by name is providing that functional/biological role.

Any tips or advice on this would be great!

Answer 1

[Alex Reynolds]

If you have the transcription factor binding sites as coordinates on your genome assembly of interest, you could use bedmap to associate them with proximal promoter regions of gene annotations, say, or of enhancers. Building a map of gene relationships would provide indirect evidence as to the general class of regulatory or functional roles of the transcription factor associated with the motif.

Answer 2

[Matthias Zepper]

I am not working in this field, but was nonetheless very impressed by the works of Aviv Regev and her lab. I found their 2019 paper intriguing and my naive take-away message was, that simply looking at an isolated motif is no longer state of the art to infer biological roles. Instead, advanced AI models are better suited to predict biological outcomes. I am aware that her team has published a tool and a companion paper lately, but can't assess the quality of the predictions. Nonetheless, I think it is worth trying out on your specific problem?

In addition, you might want to give DNA-BERT a spin?