Supplementary data to the paper: Transcription factor prediction using protein 3D secondary structures

Motivation: Transcription factors (TFs) are DNA-binding proteins that regulate gene expression. Traditional methods predict a protein as a TF if the protein contains any DNA-binding domains (DBDs) of known TFs. However, this approach fails to identify a novel TF that does not contain any known DBDs. Recently proposed TF prediction methods do not rely on DBDs. Such methods use features of protein sequences to train a machine learning model, and then use the trained model to predict whether a protein is a TF or not. Because 3-dimensional (3D) structure of a protein captures more information than its sequence, using 3D protein structures will likely allow for more accurate prediction of novel TFs.

Results: We propose a deep learning-based TF prediction method (StrucTFactor), which is the first method to utilize 3D secondary structural information of proteins. We compare StrucTFactor with recent state-of-the-art TF prediction methods based on ∼525 000 proteins across 12 datasets, capturing different aspects of data bias (including sequence redundancy) possibly influencing a method’s performance. We find that StrucTFactor significantly (p-value < 0.001) outperforms the existing TF prediction methods, improving the performance over its closest competitor by up to 17% based on Matthews correlation coefficient.