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The information about the domain architecture of proteins is useful for studying protein structure and function. However, accurate prediction of protein domain boundaries (i.e., sequence regions separating two domains) from sequence remains a significant challenge. In this work, we develop a deep learning method based on multi-head U-Nets (called DistDom) to predict protein domain boundaries utilizing 1D sequence features and predicted 2D inter-residue distance map as input. The 1D features contain the evolutionary and physicochemical information of protein sequences, whereas the 2D distance map includes the structural information of proteins that was rarely used in domain boundary prediction before. The 1D and 2D features are processed by the 1D and 2D U-Nets respectively to generate hidden features. The hidden features are then used by the multi-head attention to predict the probability of each residue of a protein being in a domain boundary, leveraging both local and global information in the features. The residue-level domain boundary predictions can be used to classify proteins as single-domain or multi-domain proteins. It classifies the CASP14 single-domain and multi-domain targets at the accuracy of 75.9%, 13.28% more accurate than the state-of-the-art method. Tested on the CASP14 multi-domain protein targets with expert annotated domain boundaries, the average per-target F1 measure score of the domain boundary prediction by DistDom is 0.263, 29.56% higher than the state-of-the-art method.
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FUpred: detecting protein domains through deep-learning-based contact map prediction
Abstract Motivation Protein domains are subunits that can fold and function independently. Correct domain boundary assignment is thus a critical step toward accurate protein structure and function analyses. There is, however, no efficient algorithm available for accurate domain prediction from sequence. The problem is particularly challenging for proteins with discontinuous domains, which consist of domain segments that are separated along the sequence. Results We developed a new algorithm, FUpred, which predicts protein domain boundaries utilizing contact maps created by deep residual neural networks coupled with coevolutionary precision matrices. The core idea of the algorithm is to retrieve domain boundary locations by maximizing the number of intra-domain contacts, while minimizing the number of inter-domain contacts from the contact maps. FUpred was tested on a large-scale dataset consisting of 2549 proteins and generated correct single- and multi-domain classifications with a Matthew’s correlation coefficient of 0.799, which was 19.1% (or 5.3%) higher than the best machine learning (or threading)-based method. For proteins with discontinuous domains, the domain boundary detection and normalized domain overlapping scores of FUpred were 0.788 and 0.521, respectively, which were 17.3% and 23.8% higher than the best control method. The results demonstrate a new avenue to accurately detect domain composition from sequence alone, especially for discontinuous, multi-domain proteins. Availability and implementation https://zhanglab.ccmb.med.umich.edu/FUpred. Supplementary information Supplementary data are available at Bioinformatics online.
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- Award ID(s):
- 1901191
- PAR ID:
- 10167320
- Date Published:
- Journal Name:
- Bioinformatics
- Volume:
- 36
- Issue:
- 12
- ISSN:
- 1367-4803
- Page Range / eLocation ID:
- 3749 to 3757
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/bioinformatics/btaa217
