Simplified Method for Predicting a Functional Class of Proteins in Transcription Factor Complexes
AuthorsPiatek, Marek J.
Schramm, Michael C.
Burra, Dharani Dhar
Jankovic, Boris R.
Archer, John A.C.
Bajic, Vladimir B.
KAUST DepartmentComputational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Applied Mathematics and Computational Science Program
Computer Science Program
Permanent link to this recordhttp://hdl.handle.net/10754/325320
MetadataShow full item record
AbstractBackground:Initiation of transcription is essential for most of the cellular responses to environmental conditions and for cell and tissue specificity. This process is regulated through numerous proteins, their ligands and mutual interactions, as well as interactions with DNA. The key such regulatory proteins are transcription factors (TFs) and transcription co-factors (TcoFs). TcoFs are important since they modulate the transcription initiation process through interaction with TFs. In eukaryotes, transcription requires that TFs form different protein complexes with various nuclear proteins. To better understand transcription regulation, it is important to know the functional class of proteins interacting with TFs during transcription initiation. Such information is not fully available, since not all proteins that act as TFs or TcoFs are yet annotated as such, due to generally partial functional annotation of proteins. In this study we have developed a method to predict, using only sequence composition of the interacting proteins, the functional class of human TF binding partners to be (i) TF, (ii) TcoF, or (iii) other nuclear protein. This allows for complementing the annotation of the currently known pool of nuclear proteins. Since only the knowledge of protein sequences is required in addition to protein interaction, the method should be easily applicable to many species.Results:Based on experimentally validated interactions between human TFs with different TFs, TcoFs and other nuclear proteins, our two classification systems (implemented as a web-based application) achieve high accuracies in distinguishing TFs and TcoFs from other nuclear proteins, and TFs from TcoFs respectively.Conclusion:As demonstrated, given the fact that two proteins are capable of forming direct physical interactions and using only information about their sequence composition, we have developed a completely new method for predicting a functional class of TF interacting protein partners with high precision and accuracy. © 2013 Piatek et al.
CitationPiatek MJ, Schramm MC, Burra DD, binShbreen A, Jankovic BR, et al. (2013) Simplified Method for Predicting a Functional Class of Proteins in Transcription Factor Complexes. PLoS ONE 8: e68857. doi:10.1371/journal.pone.0068857.
PublisherPublic Library of Science (PLoS)
PubMed Central IDPMC3709904
- TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins.
- Authors: Schaefer U, Schmeier S, Bajic VB
- Issue date: 2011 Jan
- TcoF-DB v2: update of the database of human and mouse transcription co-factors and transcription factor interactions.
- Authors: Schmeier S, Alam T, Essack M, Bajic VB
- Issue date: 2017 Jan 4
- Simplified method to predict mutual interactions of human transcription factors based on their primary structure.
- Authors: Schmeier S, Jankovic B, Bajic VB
- Issue date: 2011
- Detection of interacting transcription factors in human tissues using predicted DNA binding affinity.
- Authors: Myšičková A, Vingron M
- Issue date: 2012
- Computational identification of plant transcription factors and the construction of the PlantTFDB database.
- Authors: He K, Guo AY, Gao G, Zhu QH, Liu XC, Zhang H, Chen X, Gu X, Luo J
- Issue date: 2010
Showing items related by title, author, creator and subject.
ProDis-ContSHC: Learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrievalWang, Jim Jing-Yan; Gao, Xin; Wang, Quanquan; Li, Yongping (BMC Bioinformatics, Springer Nature, 2012-05-08) [Article]Background: The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database.Results: In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N (i) and N (j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N (i) and N (j). Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update the Protein Hierarchial Context Coherently in an iterative algorithm--ProDis-ContSHC.We test the performance of ProDis-ContSHC on two benchmark sets, i.e., the ASTRAL 1.73 database and the FSSP/DALI database. Experimental results demonstrate that plugging our supervised contextual dissimilarity measures into the retrieval systems significantly outperforms the context-free dissimilarity/similarity measures and other unsupervised contextual dissimilarity measures that do not use the class label information.Conclusions: Using the contextual proteins with their class labels in the database, we can improve the accuracy of the pairwise dissimilarity/similarity measures dramatically for the protein retrieval tasks. In this work, for the first time, we propose the idea of supervised contextual dissimilarity learning, resulting in the ProDis-ContSHC algorithm. Among different contextual dissimilarity learning approaches that can be used to compare a pair of proteins, ProDis-ContSHC provides the highest accuracy. Finally, ProDis-ContSHC compares favorably with other methods reported in the recent literature. 2012 Wang et al.; licensee BioMed Central Ltd.
CMsearch: simultaneous exploration of protein sequence space and structure space improves not only protein homology detection but also protein structure predictionCui, Xuefeng; Lu, Zhiwu; wang, sheng; Wang, Jim Jing-Yan; Gao, Xin (Bioinformatics, Oxford University Press (OUP), 2016-06-15) [Article]Motivation: Protein homology detection, a fundamental problem in computational biology, is an indispensable step toward predicting protein structures and understanding protein functions. Despite the advances in recent decades on sequence alignment, threading and alignment-free methods, protein homology detection remains a challenging open problem. Recently, network methods that try to find transitive paths in the protein structure space demonstrate the importance of incorporating network information of the structure space. Yet, current methods merge the sequence space and the structure space into a single space, and thus introduce inconsistency in combining different sources of information. Method: We present a novel network-based protein homology detection method, CMsearch, based on cross-modal learning. Instead of exploring a single network built from the mixture of sequence and structure space information, CMsearch builds two separate networks to represent the sequence space and the structure space. It then learns sequence–structure correlation by simultaneously taking sequence information, structure information, sequence space information and structure space information into consideration. Results: We tested CMsearch on two challenging tasks, protein homology detection and protein structure prediction, by querying all 8332 PDB40 proteins. Our results demonstrate that CMsearch is insensitive to the similarity metrics used to define the sequence and the structure spaces. By using HMM–HMM alignment as the sequence similarity metric, CMsearch clearly outperforms state-of-the-art homology detection methods and the CASP-winning template-based protein structure prediction methods.
Auxin efflux by PIN-FORMED proteins is activated by two different protein kinases, D6 PROTEIN KINASE and PINOIDZourelidou, Melina; Absmanner, Birgit; Weller, Benjamin; Barbosa, Inês CR; Willige, Björn C; Fastner, Astrid; Streit, Verena; Port, Sarah A; Colcombet, Jean; de la Fuente van Bentem, Sergio; Hirt, Heribert; Kuster, Bernhard; Schulze, Waltraud X; Hammes, Ulrich Z; Schwechheimer, Claus (eLife, eLife Sciences Publications, Ltd, 2014-06-19) [Article]The development and morphology of vascular plants is critically determined by synthesis and proper distribution of the phytohormone auxin. The directed cell-to-cell distribution of auxin is achieved through a system of auxin influx and efflux transporters. PIN-FORMED (PIN) proteins are proposed auxin efflux transporters, and auxin fluxes can seemingly be predicted based on the-in many cells-asymmetric plasma membrane distribution of PINs. Here, we show in a heterologous Xenopus oocyte system as well as in Arabidopsis thaliana inflorescence stems that PIN-mediated auxin transport is directly activated by D6 PROTEIN KINASE (D6PK) and PINOID (PID)/WAG kinases of the Arabidopsis AGCVIII kinase family. At the same time, we reveal that D6PKs and PID have differential phosphosite preferences. Our study suggests that PIN activation by protein kinases is a crucial component of auxin transport control that must be taken into account to understand auxin distribution within the plant.