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Location proteomics seeks to provide automated high-resolution descriptions of protein location patterns within cells. Many efforts have been undertaken in location proteomics over the past decades, thereby producing plenty of automated predictors for protein subcellular localization. However, most of these predictors are trained solely from high-throughput microscopic images or protein amino acid sequences alone. Unifying heterogeneous protein data sources has yet to be exploited. In this paper, we present a pipeline called sequence, image, network-based protein subcellular locator (SIN-Locator) that constructs a multi-view description of proteins by integrating multiple data types including images of protein expression in cells or tissues, amino acid sequences and protein–protein interaction networks, to classify the patterns of protein subcellular locations. Proteins were encoded by both handcrafted features and deep learning features, and multiple combining methods were implemented. Our experimental results indicated that optimal integrations can considerately enhance the classification accuracy, and the utility of SIN-Locator has been demonstrated through applying to new released proteins in the human protein atlas. Furthermore, we also investigate the contribution of different data sources and influence of partial absence of data. This work is anticipated to provide clues for reconciliation and combination of multi-source data for protein location analysis. [ABSTRACT FROM AUTHOR]

Given the limitation of technologies, the subcellular localizations of proteins are difficult to identify. Predicting the subcellular localization and the intercellular distribution patterns of proteins in accordance with their specific biological roles, including validated functions, relationships with other proteins, and even their specific sequence characteristics, is necessary. The computational prediction of protein subcellular localizations can be performed on the basis of the sequence and the functional characteristics. In this study, the protein–protein interaction network, functional annotation of proteins and a group of direct proteins with known subcellular localization were used to construct models. To build efficient models, several powerful machine learning algorithms, including two feature selection methods, four classification algorithms, were employed. Some key proteins and functional terms were discovered, which may provide important contributions for determining protein subcellular locations. Furthermore, some quantitative rules were established to identify the potential subcellular localizations of proteins. As the first prediction model that uses direct protein annotation information (i.e., functional features) and STRING-based protein–protein interaction network (i.e., network features), our computational model can help promote the development of predictive technologies on subcellular localizations and provide a new approach for exploring the protein subcellular localization patterns and their potential biological importance. [ABSTRACT FROM AUTHOR]

Protein subcellular localization plays a crucial role in characterizing the function of proteins and understanding various cellular processes. Therefore, accurate identification of protein subcellular location is an important yet challenging task. Numerous computational methods have been proposed to predict the subcellular location of proteins. However, most existing methods have limited capability in terms of the overall accuracy, time consumption and generalization power. To address these problems, in this study, we developed a novel computational approach based on human protein atlas (HPA) data, referred to as PScL-HDeep, for accurate and efficient image-based prediction of protein subcellular location in human tissues. We extracted different handcrafted and deep learned (by employing pretrained deep learning model) features from different viewpoints of the image. The step-wise discriminant analysis (SDA) algorithm was applied to generate the optimal feature set from each original raw feature set. To further obtain a more informative feature subset, support vector machine–based recursive feature elimination with correlation bias reduction (SVM-RFE + CBR) feature selection algorithm was applied to the integrated feature set. Finally, the classification models, namely support vector machine with radial basis function (SVM-RBF) and support vector machine with linear kernel (SVM-LNR), were learned on the final selected feature set. To evaluate the performance of the proposed method, a new gold standard benchmark training dataset was constructed from the HPA databank. PScL-HDeep achieved the maximum performance on 10-fold cross validation test on this dataset and showed a better efficacy over existing predictors. Furthermore, we also illustrated the generalization ability of the proposed method by conducting a stringent independent validation test. [ABSTRACT FROM AUTHOR]

The spatial distribution of proteome at subcellular levels provides clues for protein functions, thus is important to human biology and medicine. Imaging-based methods are one of the most important approaches for predicting protein subcellular location. Although deep neural networks have shown impressive performance in a number of imaging tasks, its application to protein subcellular localization has not been sufficiently explored. In this study, we developed a deep imaging-based approach to localize the proteins at subcellular levels. Based on deep image features extracted from convolutional neural networks (CNNs), both single-label and multi-label locations can be accurately predicted. Particularly, the multi-label prediction is quite a challenging task. Here we developed a criterion learning strategy to exploit the label–attribute relevancy and label–label relevancy. A criterion that was used to determine the final label set was automatically obtained during the learning procedure. We concluded an optimal CNN architecture that could give the best results. Besides, experiments show that compared with the hand-crafted features, the deep features present more accurate prediction with less features. The implementation for the proposed method is available at https://github.com/RanSuLab/ProteinSubcellularLocation. [ABSTRACT FROM AUTHOR]

A major challenge for protein databases is reconciling information from diverse sources. This is especially difficult when some information consists of secondary, human‐interpreted rather than primary data. For example, the Swiss‐Prot database contains curated annotations of subcellular location that are based on predictions from protein sequence, statements in scientific articles, and published experimental evidence. The Human Protein Atlas (HPA) consists of millions of high‐resolution microscopic images that show protein spatial distribution on a cellular and subcellular level. These images are manually annotated with protein subcellular locations by trained experts. The image annotations in HPA can capture the variation of subcellular location across different cell lines, tissues, or tissue states. Systematic investigation of the consistency between HPA and Swiss‐Prot assignments of subcellular location, which is important for understanding and utilizing protein location data from the two databases, has not been described previously. In this paper, we quantitatively evaluate the consistency of subcellular location annotations between HPA and Swiss‐Prot at multiple levels, as well as variation of protein locations across cell lines and tissues. Our results show that annotations of these two databases differ significantly in many cases, leading to proposed procedures for deriving and integrating the protein subcellular location data. We also find that proteins having highly variable locations are more likely to be biomarkers of diseases, providing support for incorporating analysis of subcellular location in protein biomarker identification and screening. [ABSTRACT FROM AUTHOR]

Prediction of protein subcellular location has currently become a hot topic because it has been proven to be useful for understanding both the disease mechanisms and novel drug design. With the rapid development of automated microscopic imaging technology in recent years, classification methods of bioimage-based protein subcellular location have attracted considerable attention for images can describe the protein distribution intuitively and in detail. In the current study, a prediction method of protein subcellular location was proposed based on multi-view image features that are extracted from three different views, including the four texture features of the original image, the global and local features of the protein extracted from the protein channel images after color segmentation, and the global features of DNA extracted from the DNA channel image. Finally, the extracted features were combined together to improve the performance of subcellular localization prediction. From the performance comparison of different combination features under the same classifier, the best ensemble features could be obtained. In this work, a classifier based on Stacked Auto-encoders and the random forest was also put forward. To improve the prediction results, the deep network was combined with the traditional statistical classification methods. Stringent cross-validation and independent validation tests on the benchmark dataset demonstrated the efficacy of the proposed method. [ABSTRACT FROM AUTHOR]

Background: Protein biomarkers play important roles in cancer diagnosis. Many efforts have been made on measuring abnormal expression intensity in biological samples to identity cancer types and stages. However, the change of subcellular location of proteins, which is also critical for understanding and detecting diseases, has been rarely studied. Results: In this work, we developed a machine learning model to classify protein subcellular locations based on immunohistochemistry images of human colon tissues, and validated the ability of the model to detect subcellular location changes of biomarker proteins related to colon cancer. The model uses representative image patches as inputs, and integrates feature engineering and deep learning methods. It achieves 92.69% accuracy in classification of new proteins. Two validation datasets of colon cancer biomarkers derived from published literatures and the human protein atlas database respectively are employed. It turns out that 81.82 and 65.66% of the biomarker proteins can be identified to change locations. Conclusions: Our results demonstrate that using image patches and combining predefined and deep features can improve the performance of protein subcellular localization, and our model can effectively detect biomarkers based on protein subcellular translocations. This study is anticipated to be useful in annotating unknown subcellular localization for proteins and discovering new potential location biomarkers. [ABSTRACT FROM AUTHOR]

Molecular biomarkers are changes measured in biological samples that reflect disease states. Such markers can help clinicians identify types of cancer or stages of progression, and they can guide in tailoring specific therapies. Many efforts to identify biomarkers consider genes that mutate between normal and cancerous tissues or changes in protein or RNA expression levels. Here we define location biomarkers, proteins that undergo changes in subcellular location that are indicative of disease. To discover such biomarkers, we have developed an automated pipeline to compare the subcellular location of proteins between two sets of immunohistochemistry images. We used the pipeline to compare images of healthy and tumor tissue from the Human Protein Atlas, ranking hundreds of proteins in breast, liver, prostate, and bladder based on how much their location was estimated to have changed. The performance of the system was evaluated by determining whether proteins previously known to change location in tumors were ranked highly. We present a number of candidate location biomarkers for each tissue, and identify biochemical pathways that are enriched in proteins that change location. The analysis technology is anticipated to be useful not only for discovering new location biomarkers but also for enabling automated analysis of biomarker distributions as an aid to determining diagnosis. [ABSTRACT FROM AUTHOR]

To understand the function of the encoded proteins, we need to be able to know the subcellular location of a protein. The most common method used for determining subcellular location is fluorescence microscopy which allows subcellular localizations to be imaged in high throughput. Image feature calculation has proven invaluable in the automated analysis of cellular images. This article proposes a novel method named LDPs for feature extraction based on invariant of translation and rotation from given images, the nature which is to count the local difference features of images, and the difference features are given by calculating the D-value between the gray value of the central pixel c and the gray values of eight pixels in the neighborhood. The novel method is tested on two image sets, the first set is which fluorescently tagged protein was endogenously expressed in 10 sebcellular locations, and the second set is which protein was transfected in 11 locations. A SVM was trained and tested for each image set and classification accuracies of 96.7 and 92.3 % were obtained on the endogenous and transfected sets respectively. [ABSTRACT FROM AUTHOR]

Background: In Lactic Acid Bacteria (LAB), the extracellular and surface-associated proteins can be involved in processes such as cell wall metabolism, degradation and uptake of nutrients, communication and binding to substrates or hosts. A genome-scale comparative study of these proteins (secretomes) can provide vast information towards the understanding of the molecular evolution, diversity, function and adaptation of LAB to their specific environmental niches. Results: We have performed an extensive prediction and comparison of the secretomes from 26 sequenced LAB genomes. A new approach to detect homolog clusters of secretome proteins (LaCOGs) was designed by integrating protein subcellular location prediction and homology clustering methods. The initial clusters were further adjusted semi-manually based on multiple sequence alignments, domain compositions, pseudogene analysis and biological function of the proteins. Ubiquitous protein families were identified, as well as species-specific, strain-specific, and niche-specific LaCOGs. Comparative analysis of protein subfamilies has shown that the distribution and functional specificity of LaCOGs could be used to explain many niche-specific phenotypes. A comprehensive and user-friendly database LAB-Secretome was constructed to store, visualize and update the extracellular proteins and LaCOGs http://www.cmbi.ru.nl/lab%5fsecretome/. This database will be updated regularly when new bacterial genomes become available. Conclusions: The LAB-Secretome database could be used to understand the evolution and adaptation of lactic acid bacteria to their environmental niches, to improve protein functional annotation and to serve as basis for targeted experimental studies. [ABSTRACT FROM AUTHOR]

A novel approach CE-Ploc is proposed for predicting protein subcellular locations by exploiting diversity both in feature and decision spaces. The diversity in a sequence of feature spaces is exploited using hydrophobicity and hydrophilicity of amphiphilic pseudo amino acid composition and a specific learning mechanism. Diversity in learning mechanisms is exploited by fusion of classifiers that are based on different learning mechanisms. Significant improvement in prediction performance is observed using jackknife and independent dataset tests. [ABSTRACT FROM AUTHOR]

Abstract: To understand the structure and function of a protein, an important task is to know where it occurs in the cell. Thus, a computational method for properly predicting the subcellular location of proteins would be significant in interpreting the original data produced by the large-scale genome sequencing projects. The present work tries to explore an effective method for extracting features from protein primary sequence and find a novel measurement of similarity among proteins for classifying a protein to its proper subcellular location. We considered four locations in eukaryotic cells and three locations in prokaryotic cells, which have been investigated by several groups in the past. A combined feature of primary sequence defined as a 430D (dimensional) vector was utilized to represent a protein, including 20 amino acid compositions, 400 dipeptide compositions and 10 physicochemical properties. To evaluate the prediction performance of this encoding scheme, a jackknife test based on nearest neighbor algorithm was employed. The prediction accuracies for cytoplasmic, extracellular, mitochondrial, and nuclear proteins in the former dataset were 86.3%, 89.2%, 73.5% and 89.4%, respectively, and the total prediction accuracy reached 86.3%. As for the prediction accuracies of cytoplasmic, extracellular, and periplasmic proteins in the latter dataset, the prediction accuracies were 97.4%, 86.0%, and 79.7, respectively, and the total prediction accuracy of 92.5% was achieved. The results indicate that this method outperforms some existing approaches based on amino acid composition or amino acid composition and dipeptide composition. [Copyright &y& Elsevier]