Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule
By Nawar Malhis, Eric T. C. Wong, Roy Nassar, Jörg Gsponer. 2015
52 citations recorded by the source corpus.
Motivation Intrinsically disordered regions of proteins play an essential role in the regulation of various biological processes. Key to their regulatory function is often the binding to globular protein domains via sequence elements known as molecular recognition features (MoRFs). Development of computational tools for the identification of candidate MoRF locations in amino acid sequences is an important task and an area of growing interest. Given the relative sparseness of MoRFs in protein sequences, the accuracy of the available MoRF predictors is often inadequate for practical usage, which leaves a significant need and room for improvement. In this work, we introduce MoRFCHiBi_Web, which predicts MoRF locations in protein sequences with higher accuracy compared to current MoRF predictors. Methods Three distinct and largely independent property scores are computed with component predictors and then combined to generate the final MoRF propensity scores. The first score reflects the likelihood of sequence windows to harbour MoRFs and is based on amino acid composition and sequence similarity information. It is generated by MoRFCHiBi using small windows of up to 40 residues in size. The second score identifies long stretches of protein disorder and is generated by ESpritz with the DisProt option. Lastly, the third score reflects residue conservation and is assembled from PSSM files generated by PSI-BLAST. These propensity scores are processed and then hierarchically combined using Bayes rule to generate the final MoRFCHiBi_Web predictions. Results MoRFCHiBi_Web was tested on three datasets. Results show that MoRFCHiBi_Web outperforms previously developed predictors by generating less than half the false positive rate for the same true positive rate at practical threshold values. This level of accuracy paired with its relatively high processing speed makes MoRFCHiBi_Web a practical tool for MoRF prediction. Availability http://morf.chibi.ubc.ca:8080/morf/.
Subfields: Molecular Biology
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In Molecular Biology
- Lukasz Kurgan
- Zsuzsanna Dosztányi
- Gábor Erdös
- Zhenling Peng
- Bálint Mészáros
- Vladimir N Uversky
- Jörg Gsponer
- Nawar Malhis
Citations in the corpus
- IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding (2018, methodology): “MoRFchibi also employs SVMs, but uses a dual architecture to efficiently discriminate short MoRF regions from their flanking regions and to recognize similarity to already known instances (34).”
- MoRFchibi SYSTEM: software tools for the identification of MoRFs in protein sequences (2016, methodology): “With only one of the four sub-components of MoRFCHiBi Web directly trained on its training data (13), MoRFCHiBi Web provides high scoring consistency compared to single module predictors.”
- APOD: accurate sequence-based predictor of disordered flexible linkers (2020, methodology): “These characteristics were previously used as powerful markers of functional sites (Wang and Samudrala, 2006), including functional IDRs, such as molecular recognition features (MoRFs; Disfani et al., 2012; Hanson et al., 2019; Katuwawala et al., 2019a,b,c; Malhis and Gsponer, 2015; Malhis et al., 2”