RESUMEN
The subcellular location of a protein provides valuable insights to bioinformaticians in terms of drug designs and discovery, genomics, and various other aspects of medical research. Experimental methods for protein subcellular localization determination are time-consuming and expensive, whereas computational methods, if accurate, would represent a much more efficient alternative. This article introduces an ab initio protein subcellular localization predictor based on an ensemble of Deep N-to-1 Convolutional Neural Networks. Our predictor is trained and tested on strict redundancy-reduced datasets and achieves 63% accuracy for the diverse number of classes. This predictor is a step towards bridging the gap between a protein sequence and the protein's function. It can potentially provide information about protein-protein interaction to facilitate drug design and processes like vaccine production that are essential to disease prevention.
Asunto(s)
Biología Computacional , Redes Neurales de la Computación , Biología Computacional/métodos , Proteínas/metabolismo , Proteínas/análisis , Programas Informáticos , Bases de Datos de Proteínas , HumanosRESUMEN
Subcellular localization is a critical aspect of protein function and the potential application of proteins either as drugs or drug targets, or in industrial and domestic applications. However, the experimental determination of protein localization is time consuming and expensive. Therefore, various localization predictors have been developed for particular groups of species. Intriguingly, despite their major representation amongst biotechnological cell factories and pathogens, a meta-predictor based on sorting signals and specific for Gram-positive bacteria was still lacking. Here we present GP4, a protein subcellular localization meta-predictor mainly for Firmicutes, but also Actinobacteria, based on the combination of multiple tools, each specific for different sorting signals and compartments. Novelty elements include improved cell-wall protein prediction, including differentiation of the type of interaction, prediction of non-canonical secretion pathway target proteins, separate prediction of lipoproteins and better user experience in terms of parsability and interpretability of the results. GP4 aims at mimicking protein sorting as it would happen in a bacterial cell. As GP4 is not homology based, it has a broad applicability and does not depend on annotated databases with homologous proteins. Non-canonical usage may include little studied or novel species, synthetic and engineered organisms, and even re-use of the prediction data to develop custom prediction algorithms. Our benchmark analysis highlights the improved performance of GP4 compared to other widely used subcellular protein localization predictors. A webserver running GP4 is available at http://gp4.hpc.rug.nl/.
Asunto(s)
Actinobacteria , Algoritmos , Proteínas Bacterianas , Biología Computacional , Bases de Datos de Proteínas , Firmicutes , Actinobacteria/genética , Actinobacteria/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Firmicutes/genética , Firmicutes/metabolismo , Análisis de Secuencia de ProteínaRESUMEN
The elucidation of the subcellular localization of proteins is very important in order to deeply understand their functions. In fact, proteins activities are strictly correlated to the cellular compartment and microenvironment in which they are present.In recent years, several effective and reliable proteomics techniques and computational methods have been developed and implemented in order to identify the proteins subcellular localization. This process is often time-consuming and expensive, but the recent technological and bioinformatics progress allowed the development of more accurate and simple workflows to determine the localization, interactions, and functions of proteins.In the following chapter, a brief introduction on the importance of knowing subcellular localization of proteins will be presented. Then, sample preparation protocols, proteomic methods, data analysis strategies, and software for the prediction of proteins localization will be presented and discussed. Finally, the more recent and advanced spatial proteomics techniques will be shown.
Asunto(s)
Proteómica , Transporte de Proteínas , Proteínas/metabolismo , Programas Informáticos , Fracciones Subcelulares/metabolismoRESUMEN
Protein subcellular localization prediction (PSLP), which plays an important role in the field of computational biology, identifies the position and function of proteins in cells without expensive cost and laborious effort. In the past few decades, various methods with different algorithms have been proposed in solving the problem of subcellular localization prediction; machine learning and deep learning constitute a large portion among those proposed methods. In order to provide an overview about those methods, the first part of this article will be a brief review of several state-of-the-art machine learning methods on subcellular localization prediction; then the materials used by subcellular localization prediction is described and a simple prediction method, that takes protein sequences as input and utilizes a convolutional neural network as the classifier, is introduced. At last, a list of notes is provided to indicate the major problems that may occur with this method.