What are some popular methods that go beyond using position weight matrices (PWMs) to determine putative transcription factor binding sites (TFBS)? The rate of false positives is very high so I am looking for better ways to assess the probability that a sequence is indeed a binding site.
I am looking at the promoters of a set of genes (2.5k region upstream of the transcription start site) and separately at creating a list of potential targets for certain transcription factors. I am using MotifDb to obtain PWMs for TFs in Mouse and TFBSTools to search for possible TFs that would bind in the promoter regions.
I am not interested in using pipelines such as MEME and others which leave little flexibility, I would much rather read about a method and implement it. However, I am unsure as to which would be a reliable one which would yield better results than just using PWMs.
Thank you for you help!