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Abstract Current predictors of DNA-binding residues (DBRs) from protein sequences belong to two distinct groups, those trained on binding annotations extracted from structured protein-DNA complexes (structure-trained) vs. intrinsically disordered proteins (disorder-trained). We complete the first empirical analysis of predictive performance across the structure- and disorder-annotated proteins for a representative collection of ten predictors. Majority of the structure-trained tools perform well on the structure-annotated proteins while doing relatively poorly on the disorder-annotated proteins, and vice versa. Several methods make accurate predictions for the structure-annotated proteins or the disorder-annotated proteins, but none performs highly accurately for both annotation types. Moreover, most predictors make excessive cross-predictions for the disorder-annotated proteins, where residues that interact with non-DNA ligand types are predicted as DBRs. Motivated by these results, we design, validate and deploy an innovative meta-model, hybridDBRpred, that uses deep transformer network to combine predictions generated by three best current predictors. HybridDBRpred provides accurate predictions and low levels of cross-predictions across the two annotation types, and is statistically more accurate than each of the ten tools and baseline meta-predictors that rely on averaging and logistic regression. We deploy hybridDBRpred as a convenient web server at http://biomine.cs.vcu.edu/servers/hybridDBRpred/ and provide the corresponding source code at https://github.com/jianzhang-xynu/hybridDBRpred.
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Twenty years of advances in prediction of nucleic acid-binding residues in protein sequences
Abstract Computational prediction of nucleic acid-binding residues in protein sequences is an active field of research, with over 80 methods that were released in the past 2 decades. We identify and discuss 87 sequence-based predictors that include dozens of recently published methods that are surveyed for the first time. We overview historical progress and examine multiple practical issues that include availability and impact of predictors, key features of their predictive models, and important aspects related to their training and assessment. We observe that the past decade has brought increased use of deep neural networks and protein language models, which contributed to substantial gains in the predictive performance. We also highlight advancements in vital and challenging issues that include cross-predictions between deoxyribonucleic acid (DNA)-binding and ribonucleic acid (RNA)-binding residues and targeting the two distinct sources of binding annotations, structure-based versus intrinsic disorder-based. The methods trained on the structure-annotated interactions tend to perform poorly on the disorder-annotated binding and vice versa, with only a few methods that target and perform well across both annotation types. The cross-predictions are a significant problem, with some predictors of DNA-binding or RNA-binding residues indiscriminately predicting interactions with both nucleic acid types. Moreover, we show that methods with web servers are cited substantially more than tools without implementation or with no longer working implementations, motivating the development and long-term maintenance of the web servers. We close by discussing future research directions that aim to drive further progress in this area.
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- PAR ID:
- 10567185
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Briefings in Bioinformatics
- Volume:
- 26
- Issue:
- 1
- ISSN:
- 1467-5463
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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