Protein (Multi-)Location Prediction: Using Location Inter-Dependencies in a Probabilistic Framework

Knowing the location of a protein within the cell is important for understanding its function, role in biological processes, and potential use as a drug target. Much progress has been made in developing computational methods that predict single locations for proteins, assuming that proteins localize to a single location. However, it has been shown that proteins localize to multiple locations. While a few recent systems have attempted to predict multiple locations of proteins, they typically treat locations as independent or capture inter-dependencies by treating each locations-combination present in the training set as an individual location-class. We present a new method and a preliminary system we have developed that directly incorporates inter-dependencies among locations into the multiple-location-prediction process, using a collection of Bayesian network classifiers. We evaluate our system on a dataset of single- and multi-localized proteins. Our results, obtained by incorporating inter-dependencies are significantly higher than those obtained by classifiers that do not use inter-dependencies. The performance of our system on multi-localized proteins is comparable to a top performing system (YLoc+), without restricting predictions to be based only on location-combinations present in the training set.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Protein subcellular localization prediction for Gram-negative bacteria using amino acid subalphabets and a combination of multiple support vector machines

BACKGROUND: Predicting the subcellular localization of proteins is important for determining the function of proteins. Previous works focused on predicting protein localization in Gram-negative bacteria obtained good results. However, these methods had relatively low accuracies for the localization of extracellular proteins. This paper studies ways to improve the accuracy for predicting extracellular localization in Gram-negative bacteria. RESULTS: We have developed a system for predicting the subcellular localization of proteins for Gram-negative bacteria based on amino acid subalphabets and a combination of multiple support vector machines. The recall of the extracellular site and overall recall of our predictor reach 86.0% and 89.8%, respectively, in 5-fold cross-validation. To the best of our knowledge, these are the most accurate results for predicting subcellular localization in Gram-negative bacteria. CONCLUSION: Clustering 20 amino acids into a few groups by the proposed greedy algorithm provides a new way to extract features from protein sequences to cover more adjacent amino acids and hence reduce the dimensionality of the input vector of protein features. It was observed that a good amino acid grouping leads to an increase in prediction performance. Furthermore, a proper choice of a subset of complementary support vector machines constructed by different features of proteins maximizes the prediction accuracy

SChloro: directing Viridiplantae proteins to six chloroplastic sub-compartments

Motivation: Chloroplasts are organelles found in plants and involved in several important cell processes. Similarly to other compartments in the cell, chloroplasts have an internal structure comprising several sub-compartments, where different proteins are targeted to perform their functions. Given the relation between protein function and localization, the availability of effective computational tools to predict protein sub-organelle localizations is crucial for large-scale functional studies. Results: In this paper we present SChloro, a novel machine-learning approach to predict protein sub-chloroplastic localization, based on targeting signal detection and membrane protein information. The proposed approach performs multi-label predictions discriminating six chloroplastic sub-compartments that include inner membrane, outer membrane, stroma, thylakoid lumen, plastoglobule and thylakoid membrane. In comparative benchmarks, the proposed method outperforms current state-of-the-art methods in both single-and multi-compartment predictions, with an overall multi-label accuracy of 74%. The results demonstrate the relevance of the approach that is eligible as a good candidate for integration into more general large-scale annotation pipelines of protein subcellular localization

Minimalist Ensemble Algorithms for Genome-Wide Protein Localization Prediction

Background Computational prediction of protein subcellular localization can greatly help to elucidate its functions. Despite the existence of dozens of protein localization prediction algorithms, the prediction accuracy and coverage are still low. Several ensemble algorithms have been proposed to improve the prediction performance, which usually include as many as 10 or more individual localization algorithms. However, their performance is still limited by the running complexity and redundancy among individual prediction algorithms. Results This paper proposed a novel method for rational design of minimalist ensemble algorithms for practical genome-wide protein subcellular localization prediction. The algorithm is based on combining a feature selection based filter and a logistic regression classifier. Using a novel concept of contribution scores, we analyzed issues of algorithm redundancy, consensus mistakes, and algorithm complementarity in designing ensemble algorithms. We applied the proposed minimalist logistic regression (LR) ensemble algorithm to two genome-wide datasets of Yeast and Human and compared its performance with current ensemble algorithms. Experimental results showed that the minimalist ensemble algorithm can achieve high prediction accuracy with only 1/3 to 1/2 of individual predictors of current ensemble algorithms, which greatly reduces computational complexity and running time. It was found that the high performance ensemble algorithms are usually composed of the predictors that together cover most of available features. Compared to the best individual predictor, our ensemble algorithm improved the prediction accuracy from AUC score of 0.558 to 0.707 for the Yeast dataset and from 0.628 to 0.646 for the Human dataset. Compared with popular weighted voting based ensemble algorithms, our classifier-based ensemble algorithms achieved much better performance without suffering from inclusion of too many individual predictors. Conclusions We proposed a method for rational design of minimalist ensemble algorithms using feature selection and classifiers. The proposed minimalist ensemble algorithm based on logistic regression can achieve equal or better prediction performance while using only half or one-third of individual predictors compared to other ensemble algorithms. The results also suggested that meta-predictors that take advantage of a variety of features by combining individual predictors tend to achieve the best performance. The LR ensemble server and related benchmark datasets are available at http://mleg.cse.sc.edu/LRensemble/cgi-bin/predict.cgi

Machine learning methods for omics data integration

High-throughput technologies produce genome-scale transcriptomic and metabolomic (omics) datasets that allow for the system-level studies of complex biological processes. The limitation lies in the small number of samples versus the larger number of features represented in these datasets. Machine learning methods can help integrate these large-scale omics datasets and identify key features from each dataset. A novel class dependent feature selection method integrates the F statistic, maximum relevance binary particle swarm optimization (MRBPSO), and class dependent multi-category classification (CDMC) system. A set of highly differentially expressed genes are pre-selected using the F statistic as a filter for each dataset. MRBPSO and CDMC function as a wrapper to select desirable feature subsets for each class and classify the samples using those chosen class-dependent feature subsets. The results indicate that the class-dependent approaches can effectively identify unique biomarkers for each cancer type and improve classification accuracy compared to class independent feature selection methods. The integration of transcriptomics and metabolomics data is based on a classification framework. Compared to principal component analysis and non-negative matrix factorization based integration approaches, our proposed method achieves 20-30% higher prediction accuracies on Arabidopsis tissue development data. Metabolite-predictive genes and gene-predictive metabolites are selected from transcriptomic and metabolomic data respectively. The constructed gene-metabolite correlation network can infer the functions of unknown genes and metabolites. Tissue-specific genes and metabolites are identified by the class-dependent feature selection method. Evidence from subcellular locations, gene ontology, and biochemical pathways support the involvement of these entities in different developmental stages and tissues in Arabidopsis

The Trypanosoma brucei MitoCarta and its regulation and splicing pattern during development

It has long been known that trypanosomes regulate mitochondrial biogenesis during the life cycle of the parasite; however, the mitochondrial protein inventory (MitoCarta) and its regulation remain unknown. We present a novel computational method for genome-wide prediction of mitochondrial proteins using a support vector machine-based classifier with ∼90% prediction accuracy. Using this method, we predicted the mitochondrial localization of 468 proteins with high confidence and have experimentally verified the localization of a subset of these proteins. We then applied a recently developed parallel sequencing technology to determine the expression profiles and the splicing patterns of a total of 1065 predicted MitoCarta transcripts during the development of the parasite, and showed that 435 of the transcripts significantly changed their expressions while 630 remain unchanged in any of the three life stages analyzed. Furthermore, we identified 298 alternatively splicing events, a small subset of which could lead to dual localization of the corresponding proteins

The Trypanosoma \u3ci\u3ebrucei\u3c/i\u3e MitoCarta and its regulation and splicing pattern during development

It has long been known that trypanosomes regulate mitochondrial biogenesis during the life cycle of the parasite; however, the mitochondrial protein inventory (MitoCarta) and its regulation remain unknown. We present a novel computational method for genome-wide prediction of mitochondrial proteins using a support vector machine-based classifier with ~90% prediction accuracy. Using this method, we predicted the mitochondrial localization of 468 proteins with high confidence and have experimentally verified the localization of a subset of these proteins. We then applied a recently developed parallel sequencing technology to determine the expression profiles and the splicing patterns of a total of 1065 predicted MitoCarta transcripts during the development of the parasite, and showed that 435 of the transcripts significantly changed their expressions while 630 remain unchanged in any of the three life stages analyzed. Furthermore, we identified 298 alternatively splicing events, a small subset of which could lead to dual localization of the corresponding proteins

Many Local Pattern Texture Features: Which Is Better for Image-Based Multilabel Human Protein Subcellular Localization Classification?

Human protein subcellular location prediction can provide critical knowledge for understanding a protein’s function. Since significant progress has been made on digital microscopy, automated image-based protein subcellular location classification is urgently needed. In this paper, we aim to investigate more representative image features that can be effectively used for dealing with the multilabel subcellular image samples. We prepared a large multilabel immunohistochemistry (IHC) image benchmark from the Human Protein Atlas database and tested the performance of different local texture features, including completed local binary pattern, local tetra pattern, and the standard local binary pattern feature. According to our experimental results from binary relevance multilabel machine learning models, the completed local binary pattern, and local tetra pattern are more discriminative for describing IHC images when compared to the traditional local binary pattern descriptor. The combination of these two novel local pattern features and the conventional global texture features is also studied. The enhanced performance of final binary relevance classification model trained on the combined feature space demonstrates that different features are complementary to each other and thus capable of improving the accuracy of classification