Prediction Of Protein Subcellular Localization Research Articles

Layered Approach for Predicting Protein Subcellular Localization in Yeast Microarray Data

Subcellular localization is a well-designed representation of proteins. We need a fully automatic and reliable prediction system for protein subcellular localization, especially for the analysis of large-scale of yeast microarray data. In this paper we consider the dataset with multi classes and propose the classification for each location of protein subcellular in a separate layer. In this work, a multi-classification approach for subcellular localization is designed and developed to achieve high efficiency and improve the prediction and classification accuracy. The rule based Ripper method has been found to predict the subcellular localization of proteins from their protein microarray data, compared to other classifiers.

Predict Subcellular Locations of Singleplex and Multiplex Proteins by Semi-Supervised Learning and Dimension-Reducing General Mode of Chou's PseAAC

Predicting protein subcellular location is one of major challenges in Bioinformatics area since such knowledge helps us understand protein functions and enables us to select the targeted proteins during drug discovery process. While many computational techniques have been proposed to improve predictive performance for protein subcellular location, they have several shortcomings. In this work, we propose a method to solve three main issues in such techniques; i) manipulation of multiplex proteins which may exist or move between multiple cellular compartments, ii) handling of high dimensionality in input and output spaces and iii) requirement of sufficient labeled data for model training. Towards these issues, this work presents a new computational method for predicting proteins which have either single or multiple locations. The proposed technique, namely iFLAST-CORE, incorporates the dimensionality reduction in the feature and label spaces with co-training paradigm for semi-supervised multi-label classification. For this purpose, the Singular Value Decomposition (SVD) is applied to transform the high-dimensional feature space and label space into the lower-dimensional spaces. After that, due to limitation of labeled data, the co-training regression makes use of unlabeled data by predicting the target values in the lower-dimensional spaces of unlabeled data. In the last step, the component of SVD is used to project labels in the lower-dimensional space back to those in the original space and an adaptive threshold is used to map a numeric value to a binary value for label determination. A set of experiments on viral proteins and gram-negative bacterial proteins evidence that our proposed method improve the classification performance in terms of various evaluation metrics such as Aiming (or Precision), Coverage (or Recall) and macro F-measure, compared to the traditional method that uses only labeled data.

A novel approach for protein subcellular location prediction using amino acid exposure

BackgroundProteins perform their functions in associated cellular locations. Therefore, the study of protein function can be facilitated by predictions of protein location. Protein location can be predicted either from the sequence of a protein alone by identification of targeting peptide sequences and motifs, or by homology to proteins of known location. A third approach, which is complementary, exploits the differences in amino acid composition of proteins associated to different cellular locations, and can be useful if motif and homology information are missing. Here we expand this approach taking into account amino acid composition at different levels of amino acid exposure.ResultsOur method has two stages. For stage one, we trained multiple Support Vector Machines (SVMs) to score eukaryotic protein sequences for membership to each of three categories: nuclear, cytoplasmic and extracellular, plus extra category nucleocytoplasmic, accounting for the fact that a large number of proteins shuttles between those two locations. In stage two we use an artificial neural network (ANN) to propose a category from the scores given to the four locations in stage one. The method reaches an accuracy of 68% when using as input 3D-derived values of amino acid exposure. Calibration of the method using predicted values of amino acid exposure allows classifying proteins without 3D-information with an accuracy of 62% and discerning proteins in different locations even if they shared high levels of identity.ConclusionsIn this study we explored the relationship between residue exposure and protein subcellular location. We developed a new algorithm for subcellular location prediction that uses residue exposure signatures. Our algorithm uses a novel approach to address the multiclass classification problem. The algorithm is implemented as web server 'NYCE’ and can be accessed at http://cbdm.mdc-berlin.de/~amer/nyce.

Image-based classification of protein subcellular location patterns in human reproductive tissue by ensemble learning global and local features

The reproductive system is a specific system of organs working together for the purpose of reproduction. As one of the most significant characteristics of human cell, subcellular localization plays a critical role for understanding specific functions of mammalian proteins. In this study, we developed a novel computational protocol for predicting protein subcellular locations from microscope images of cells in human reproductive tissues. Three major steps are contained in this protocol, i.e., protein object identification, image feature extraction, and classification. We first separated protein and DNA staining in the images with both linear and non-negative matrix factorization separation methods; then we extracted protein multi-view global and local texture features including wavelet Haralick, local binary patterns, local ternary patterns, and the local quinary patterns; finally based on the selected important feature subset, we constructed an ensemble classifier with support vector machines for classifications. Experiments are performed on a benchmark dataset consisting of seven major subcellular classes in human reproductive tissues collected from human protein atlas. Our results show that the local texture pattern features play an important complementary role to global features for enhancing the prediction performance. An overall accuracy of 85% is obtained through current system, and when only confident classifications are considered, the accuracy can reach 99%. It is the first developed image based protein subcellular location predictor specifically for human reproductive tissue. The promising results indicate that the developed protocol can be applied for accurate large-scale protein subcellular localization annotations in human reproductive system.

SCLpredT: Ab initio and homology-based prediction of subcellular localization by N-to-1 neural networks

The prediction of protein subcellular localization is a important step towards the prediction of protein function, and considerable effort has gone over the last decade into the development of computational predictors of protein localization. In this article we design a new predictor of protein subcellular localization, based on a Machine Learning model (N-to-1 Neural Networks) which we have recently developed. This system, in three versions specialised, respectively, on Plants, Fungi and Animals, has a rich output which incorporates the class “organelle” alongside cytoplasm, nucleus, mitochondria and extracellular, and, additionally, chloroplast in the case of Plants. We investigate the information gain of introducing additional inputs, including predicted secondary structure, and localization information from homologous sequences. To accommodate the latter we design a new algorithm which we present here for the first time. While we do not observe any improvement when including predicted secondary structure, we measure significant overall gains when adding homology information. The final predictor including homology information correctly predicts 74%, 79% and 60% of all proteins in the case of Fungi, Animals and Plants, respectively, and outperforms our previous, state-of-the-art predictor SCLpred, and the popular predictor BaCelLo. We also observe that the contribution of homology information becomes dominant over sequence information for sequence identity values exceeding 50% for Animals and Fungi, and 60% for Plants, confirming that subcellular localization is less conserved than structure.SCLpredT is publicly available at http://distillf.ucd.ie/sclpredt/. Sequence- or template-based predictions can be obtained, and up to 32kbytes of input can be processed in a single submission.

Predicting Protein Subcellular Localization Using the Algorithm of Diversity Finite Coefficient Combined with Artificial Neural Network

Protein subcellular localization is an important research field of bioinformatics. The subcellular localization of proteins classification problem is transformed into several two classification problems with error-correcting output codes. In this paper, we use the algorithm of the increment of diversity combined with artificial neural network to predict protein in SNL6 which has six subcelluar localizations. The prediction ability was evaluated by 5-jackknife cross-validation. Its predicted result is 81.3%. By com-paring its results with other methods, it indicates the new approach is feasible and effective.

Predicting Protein Subcellular Localization Using the Algorithm of Increment of Diversity Combined with Weighted K-Nearest Neighbor

Protein subcellular localization is an important research field of bioinformatics. In this paper, we use the algorithm of the increment of diversity combined with weighted K nearest neighbor to predict protein in SNL6 which has six subcelluar localizations and SNL9 which has nine subcelluar localizations. We use the increment of diversity to extract diversity finite coefficient as new features of proteins. And the basic classifier is weighted K-nearest neighbor. The prediction ability was evaluated by 5-jackknife cross-validation. Its predicted result is 83.3% for SNL6 and 87.6 % for SNL9. By comparing its results with other methods, it indicates the new approach is feasible and effective.

Predicting protein subchloroplast locations with both single and multiple sites via three different modes of Chou's pseudo amino acid compositions

Owing to the fact that location information can indicate important functionalities of proteins, developing computational tools to predict protein subcellular localization is one of the most efficient and meaningful tasks with no doubt. The existence methods dealing with prediction of protein subchloroplast locations can only handle the case of single location site. Therefore, it is meaningful and challenging to make effort in how to deal with the proteins with multiple subchloroplast location sites instead of just excluding them. To solve this problem, new systems for predicting protein subchloroplast localization with single or multiple sites are developed and discussed in the paper. Three different editions of KNN algorithms and four different types of feature extraction were adopted to construct the prediction systems. This is the first effort to predict the proteins with multiple subchloroplast locations. The overall jackknife success rates achieved by the best combination (features+classifier) on three dataset with different levels of homology were 89.08%, 81.29% and 71.11%. The performance of the prediction models indicate that the proposed methods might be applied as a useful and efficient assistant tool for the prediction of sub-subcellular localizations.

Mining Proteins with Non-Experimental Annotations Based on an Active Sample Selection Strategy for Predicting Protein Subcellular Localization

Subcellular localization of a protein is important to understand proteins’ functions and interactions. There are many techniques based on computational methods to predict protein subcellular locations, but it has been shown that many prediction tasks have a training data shortage problem. This paper introduces a new method to mine proteins with non-experimental annotations, which are labeled by non-experimental evidences of protein databases to overcome the training data shortage problem. A novel active sample selection strategy is designed, taking advantage of active learning technology, to actively find useful samples from the entire data pool of candidate proteins with non-experimental annotations. This approach can adequately estimate the “value” of each sample, automatically select the most valuable samples and add them into the original training set, to help to retrain the classifiers. Numerical experiments with for four popular multi-label classifiers on three benchmark datasets show that the proposed method can effectively select the valuable samples to supplement the original training set and significantly improve the performances of predicting classifiers.

An image-based multi-label human protein subcellular localization predictor (iLocator) reveals protein mislocalizations in cancer tissues

Human cells are organized into compartments of different biochemical cellular processes. Having proteins appear at the right time to the correct locations in the cellular compartments is required to conduct their functions in normal cells, whereas mislocalization of proteins can result in pathological diseases, including cancer. To reveal the cancer-related protein mislocalizations, we developed an image-based multi-label subcellular location predictor, iLocator, which covers seven cellular localizations. The iLocator incorporates both global and local image descriptors and generates predictions by using an ensemble multi-label classifier. The algorithm has the ability to treat both single- and multiple-location proteins. We first trained and tested iLocator on 3240 normal human tissue images that have known subcellular location information from the human protein atlas. The iLocator was then used to generate protein localization predictions for 3696 protein images from seven cancer tissues that have no location annotations in the human protein atlas. By comparing the output data from normal and cancer tissues, we detected eight potential cancer biomarker proteins that have significant localization differences with P-value < 0.01. http://www.csbio.sjtu.edu.cn/bioinf/iLocator/

Predicting multisite protein subcellular locations: progress and challenges

In the last two decades, predicting protein subcellular locations has become a hot topic in bioinformatics. A number of algorithms and online services have been developed to computationally assign a subcellular location to a given protein sequence. With the progress of many proteome projects, more and more proteins are annotated with more than one subcellular location. However, multisite prediction has only been considered in a handful of recent studies, in which there are several common challenges. In this special report, the authors discuss what these challenges are, why these challenges are important and how the existing studies gave their solutions. Finally, a vision of the future of predicting multisite protein subcellular locations is given.

Using radial basis function on the general form of Chou's pseudo amino acid composition and PSSM to predict subcellular locations of proteins with both single and multiple sites

Prediction of protein subcellular location is a meaningful task which attracted much attention in recent years. A lot of protein subcellular location predictors which can only deal with the single-location proteins were developed. However, some proteins may belong to two or even more subcellular locations. It is important to develop predictors which will be able to deal with multiplex proteins, because these proteins have extremely useful implication in both basic biological research and drug discovery. Considering the circumstance that the number of methods dealing with multiplex proteins is limited, it is meaningful to explore some new methods which can predict subcellular location of proteins with both single and multiple sites. Different methods of feature extraction and different models of predict algorithms using on different benchmark datasets may receive some general results. In this paper, two different feature extraction methods and two different models of neural networks were performed on three benchmark datasets of different kinds of proteins, i.e. datasets constructed specially for Gram-positive bacterial proteins, plant proteins and virus proteins. These benchmark datasets have different number of location sites. The application result shows that RBF neural network has apparently superiorities against BP neural network on these datasets no matter which type of feature extraction is chosen.

Protein localization prediction using random walks on graphs.

BackgroundUnderstanding the localization of proteins in cells is vital to characterizing their functions and possible interactions. As a result, identifying the (sub)cellular compartment within which a protein is located becomes an important problem in protein classification. This classification issue thus involves predicting labels in a dataset with a limited number of labeled data points available. By utilizing a graph representation of protein data, random walk techniques have performed well in sequence classification and functional prediction; however, this method has not yet been applied to protein localization. Accordingly, we propose a novel classifier in the site prediction of proteins based on random walks on a graph.ResultsWe propose a graph theory model for predicting protein localization using data generated in yeast and gram-negative (Gneg) bacteria. We tested the performance of our classifier on the two datasets, optimizing the model training parameters by varying the laziness values and the number of steps taken during the random walk. Using 10-fold cross-validation, we achieved an accuracy of above 61% for yeast data and about 93% for gram-negative bacteria.ConclusionsThis study presents a new classifier derived from the random walk technique and applies this classifier to investigate the cellular localization of proteins. The prediction accuracy and additional validation demonstrate an improvement over previous methods, such as support vector machine (SVM)-based classifiers.

Identifying the singleplex and multiplex proteins based on transductive learning for protein subcellular localization prediction

A new method is proposed to identify whether a query protein is singleplex or multiplex for improving the quality of protein subcellular localization prediction. Based on the transductive learning technique, this approach utilizes the information from the both query proteins and known proteins to estimate the subcellular location number of every query protein so that the singleplex and multiplex proteins can be recognized and distinguished. Each query protein is then dealt with by a targeted single-label or multi-label predictor to achieve a high-accuracy prediction result. We assess the performance of the proposed approach by applying it to three groups of protein sequences datasets. Simulation experiments show that the proposed approach can effectively identify the singleplex and multiplex proteins. Through a comparison, the reliably of this method for enhancing the power of predicting protein subcellular localization can also be verified.

A Compact Hybrid Feature Vector for an Accurate Prediction of Protein Subcellular Location

A Compact Hybrid Feature Vector for an Accurate Prediction of Protein Subcellular Location

Multilabel Learning via Random Label Selection for Protein Subcellular Multilocations Prediction

Prediction of protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods are only used to deal with the single-location proteins. In the past few years, only a few methods have been proposed to tackle proteins with multiple locations. However, they only adopt a simple strategy, that is, transforming the multilocation proteins to multiple proteins with single location, which does not take correlations among different subcellular locations into account. In this paper, a novel method named random label selection (RALS) (multilabel learning via RALS), which extends the simple binary relevance (BR) method, is proposed to learn from multilocation proteins in an effective and efficient way. RALS does not explicitly find the correlations among labels, but rather implicitly attempts to learn the label correlations from data by augmenting original feature space with randomly selected labels as its additional input features. Through the fivefold cross-validation test on a benchmark data set, we demonstrate our proposed method with consideration of label correlations obviously outperforms the baseline BR method without consideration of label correlations, indicating correlations among different subcellular locations really exist and contribute to improvement of prediction performance. Experimental results on two benchmark data sets also show that our proposed methods achieve significantly higher performance than some other state-of-the-art methods in predicting subcellular multilocations of proteins. The prediction web server is available at http://levis.tongji.edu.cn:8080/bioinfo/MLPred-Euk/ for the public usage.

Protein Function Prediction using Text-based Features extracted from the Biomedical Literature: The CAFA Challenge

BackgroundAdvances in sequencing technology over the past decade have resulted in an abundance of sequenced proteins whose function is yet unknown. As such, computational systems that can automatically predict and annotate protein function are in demand. Most computational systems use features derived from protein sequence or protein structure to predict function. In an earlier work, we demonstrated the utility of biomedical literature as a source of text features for predicting protein subcellular location. We have also shown that the combination of text-based and sequence-based prediction improves the performance of location predictors. Following up on this work, for the Critical Assessment of Function Annotations (CAFA) Challenge, we developed a text-based system that aims to predict molecular function and biological process (using Gene Ontology terms) for unannotated proteins. In this paper, we present the preliminary work and evaluation that we performed for our system, as part of the CAFA challenge.ResultsWe have developed a preliminary system that represents proteins using text-based features and predicts protein function using a k-nearest neighbour classifier (Text-KNN). We selected text features for our classifier by extracting key terms from biomedical abstracts based on their statistical properties. The system was trained and tested using 5-fold cross-validation over a dataset of 36,536 proteins. System performance was measured using the standard measures of precision, recall, F-measure and overall accuracy. The performance of our system was compared to two baseline classifiers: one that assigns function based solely on the prior distribution of protein function (Base-Prior) and one that assigns function based on sequence similarity (Base-Seq). The overall prediction accuracy of Text-KNN, Base-Prior, and Base-Seq for molecular function classes are 62%, 43%, and 58% while the overall accuracy for biological process classes are 17%, 11%, and 28% respectively. Results obtained as part of the CAFA evaluation itself on the CAFA dataset are reported as well.ConclusionsOur evaluation shows that the text-based classifier consistently outperforms the baseline classifier that is based on prior distribution, and typically has comparable performance to the baseline classifier that uses sequence similarity. Moreover, the results suggest that combining text features with other types of features can potentially lead to improved prediction performance. The preliminary results also suggest that while our text-based classifier can be used to predict both molecular function and biological process in which a protein is involved, the classifier performs significantly better for predicting molecular function than for predicting biological process. A similar trend was observed for other classifiers participating in the CAFA challenge.

GOASVM: A subcellular location predictor by incorporating term-frequency gene ontology into the general form of Chou's pseudo-amino acid composition

Prediction of protein subcellular localization is an important yet challenging problem. Recently, several computational methods based on Gene Ontology (GO) have been proposed to tackle this problem and have demonstrated superiority over methods based on other features. Existing GO-based methods, however, do not fully use the GO information. This paper proposes an efficient GO method called GOASVM that exploits the information from the GO term frequencies and distant homologs to represent a protein in the general form of Chou's pseudo-amino acid composition. The method first selects a subset of relevant GO terms to form a GO vector space. Then for each protein, the method uses the accession number (AC) of the protein or the ACs of its homologs to find the number of occurrences of the selected GO terms in the Gene Ontology annotation (GOA) database as a means to construct GO vectors for support vector machines (SVMs) classification. With the advantages of GO term frequencies and a new strategy to incorporate useful homologous information, GOASVM can achieve a prediction accuracy of 72.2% on a new independent test set comprising novel proteins that were added to Swiss-Prot six years later than the creation date of the training set. GOASVM and Supplementary materials are available online at http://bioinfo.eie.polyu.edu.hk/mGoaSvmServer/GOASVM.html.

ILoc-Animal: a multi-label learning classifier for predicting subcellular localization of animal proteins

Predicting protein subcellular localization is a challenging problem, particularly when query proteins have multi-label features meaning that they may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing methods can only be used to deal with the single-label proteins. Actually, multi-label proteins should not be ignored because they usually bear some special function worthy of in-depth studies. By introducing the "multi-label learning" approach, a new predictor, called iLoc-Animal, has been developed that can be used to deal with the systems containing both single- and multi-label animal (metazoan except human) proteins. Meanwhile, to measure the prediction quality of a multi-label system in a rigorous way, five indices were introduced; they are "Absolute-True", "Absolute-False" (or Hamming-Loss"), "Accuracy", "Precision", and "Recall". As a demonstration, the jackknife cross-validation was performed with iLoc-Animal on a benchmark dataset of animal proteins classified into the following 20 location sites: (1) acrosome, (2) cell membrane, (3) centriole, (4) centrosome, (5) cell cortex, (6) cytoplasm, (7) cytoskeleton, (8) endoplasmic reticulum, (9) endosome, (10) extracellular, (11) Golgi apparatus, (12) lysosome, (13) mitochondrion, (14) melanosome, (15) microsome, (16) nucleus, (17) peroxisome, (18) plasma membrane, (19) spindle, and (20) synapse, where many proteins belong to two or more locations. For such a complicated system, the outcomes achieved by iLoc-Animal for all the aforementioned five indices were quite encouraging, indicating that the predictor may become a useful tool in this area. It has not escaped our notice that the multi-label approach and the rigorous measurement metrics can also be used to investigate many other multi-label problems in molecular biology. As a user-friendly web-server, iLoc-Animal is freely accessible to the public at the web-site .

Virus-ECC-mPLoc: A Multi-Label Predictor for Predicting the Subcellular Localization of Virus Proteins with Both Single and Multiple Sites Based on a General Form of Chou&amp;apos;s Pseudo Amino Acid Composition

Protein subcellular localization aims at predicting the location of a protein within a cell using computational methods. Knowledge of subcellular localization of viral proteins in a host cell or virus-infected cell is important because it is closely related to their destructive tendencies and consequences. Prediction of viral protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods specialized for viral proteins are only used to deal with the single-location proteins. To better reflect the characteristics of multiplex proteins, a new predictor, called Virus-ECC-mPLoc, has been developed that can be used to deal with the systems containing both singleplex and multiplex proteins by introducing a powerful multi-label learning approach which exploits correlations between subcellular locations and by hybridizing the gene ontology information with the dipeptide composition information. It can be utilized to identify viral proteins among the following six locations: (1) viral capsid, (2) host cell membrane, (3) host endoplasmic reticulum, (4) host cytoplasm, (5) host nucleus, and (6) secreted. Experimental results show that the overall success rates thus obtained by Virus-ECC-mPLoc are 86.9% for jackknife test and 87.2% for independent data set test, which are significantly higher than that by any of the existing predictors. As a user-friendly web-server, Virus-ECCmPLoc is freely accessible to the public at the web-site http://levis.tongji.edu.cn:8080/bioinfo/Virus-ECC-mPLoc/.