XGBoost Improves Classification of MGMT Promoter Methylation Status in IDH1 Wildtype Glioblastoma.

Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.

Classifying Promoters by Interpreting the Hidden Information of DNA Sequences via Deep Learning and Combination of Continuous FastText N-Grams.

A promoter is a short region of DNA (100-1,000 bp) where transcription of a gene by RNA polymerase begins. It is typically located directly upstream or at the 5' end of the transcription initiation site. DNA promoter has been proven to be the primary cause of many human diseases, especially diabetes, cancer, or Huntington's disease. Therefore, classifying promoters has become an interesting problem and it has attracted the attention of a lot of researchers in the bioinformatics field. There were a variety of studies conducted to resolve this problem, however, their performance results still require further improvement. In this study, we will present an innovative approach by interpreting DNA sequences as a combination of continuous FastText N-grams, which are then fed into a deep neural network in order to classify them. Our approach is able to attain a cross-validation accuracy of 85.41 and 73.1% in the two layers, respectively. Our results outperformed the state-of-the-art methods on the same dataset, especially in the second layer (strength classification). Throughout this study, promoter regions could be identified with high accuracy and it provides analysis for further biological research as well as precision medicine. In addition, this study opens new paths for the natural language processing application in omics data in general and DNA sequences in particular.

Identification of clathrin proteins by incorporating hyperparameter optimization in deep learning and PSSM profiles.

BACKGROUND AND OBJECTIVES: Clathrin is an adaptor protein that serves as the principal element of the vesicle-coating complex and is important for the membrane cleavage to dispense the invaginated vesicle from the plasma membrane. The functional loss of clathrins has been tied to a lot of human diseases, i.e., neurodegenerative disorders, cancer, Alzheimer's diseases, and so on. Therefore, creating a precise model to identify its functions is a crucial step towards understanding human diseases and designing drug targets. METHODS: We present a deep learning model using a two-dimensional convolutional neural network (CNN) and position-specific scoring matrix (PSSM) profiles to identify clathrin proteins from high throughput sequences. Traditionally, the 2D CNNs take images as an input so we treated the PSSM profile with a 20 × 20 matrix as an image of 20 × 20 pixels. The input PSSM profile was then connected to our 2D CNN in which we set a variety of parameters to improve the performance of the model. Based on the 10-fold cross-validation results, hyper-parameter optimization process was employed to find the best model for our dataset. Finally, an independent dataset was used to assess the predictive ability of the current model. RESULTS: Our model could identify clathrin proteins with sensitivity of 92.2%, specificity of 91.2%, accuracy of 91.8%, and MCC of 0.83 in the independent dataset. Compared to state-of-the-art traditional neural networks, our method achieved a significant improvement in all typical measurement metrics. CONCLUSIONS: Throughout the proposed study, we provide an effective tool for investigating clathrin proteins and our achievement could promote the use of deep learning in biomedical research. We also provide source codes and dataset freely at https://www.github.com/khanhlee/deep-clathrin/.

ET-GRU: using multi-layer gated recurrent units to identify electron transport proteins.

BACKGROUND: Electron transport chain is a series of protein complexes embedded in the process of cellular respiration, which is an important process to transfer electrons and other macromolecules throughout the cell. It is also the major process to extract energy via redox reactions in the case of oxidation of sugars. Many studies have determined that the electron transport protein has been implicated in a variety of human diseases, i.e. diabetes, Parkinson, Alzheimer's disease and so on. Few bioinformatics studies have been conducted to identify the electron transport proteins with high accuracy, however, their performance results require a lot of improvements. Here, we present a novel deep neural network architecture to address this problem. RESULTS: Most of the previous studies could not use the original position specific scoring matrix (PSSM) profiles to feed into neural networks, leading to a lack of information and the neural networks consequently could not achieve the best results. In this paper, we present a novel approach by using deep gated recurrent units (GRU) on full PSSMs to resolve this problem. Our approach can precisely predict the electron transporters with the cross-validation and independent test accuracy of 93.5 and 92.3%, respectively. Our approach demonstrates superior performance to all of the state-of-the-art predictors on electron transport proteins. CONCLUSIONS: Through the proposed study, we provide ET-GRU, a web server for discriminating electron transport proteins in particular and other protein functions in general. Also, our achievement could promote the use of GRU in computational biology, especially in protein function prediction.

iMotor-CNN: Identifying molecular functions of cytoskeleton motor proteins using 2D convolutional neural network via Chou's 5-step rule.

Motor proteins are the driving force behind muscle contraction and are responsible for the active transportation of most proteins and vesicles in the cytoplasm. There are three superfamilies of cytoskeletal motor proteins with various molecular functions and structures: dynein, kinesin, and myosin. The functional loss of a specific motor protein molecular function has linked to a variety of human diseases, e.g., Charcot-Marie-Tooth disease, kidney disease. Therefore, creating a precise model to classify motor proteins is essential for helping biologists understand their molecular functions and design drug targets according to their impact on human diseases. Here we attempt to classify cytoskeleton motor proteins using deep learning, which has been increasingly and widely used to address numerous problems in a variety of fields resulting in state-of-the-art results. Our effective deep convolutional neural network is able to achieve an independent test accuracy of 97.5%, 96.4%, and 96.1% for each superfamily, respectively. Compared to other state-of-the-art methods, our approach showed a significant improvement in performance across a range of evaluation metrics. Through the proposed study, we provide an effective model for classifying motor proteins and a basis for further research that can enhance the performance of protein function classification using deep learning.

iEnhancer-5Step: Identifying enhancers using hidden information of DNA sequences via Chou's 5-step rule and word embedding.

An enhancer is a short (50-1500bp) region of DNA that plays an important role in gene expression and the production of RNA and proteins. Genetic variation in enhancers has been linked to many human diseases, such as cancer, disorder or inflammatory bowel disease. Due to the importance of enhancers in genomics, the classification of enhancers has become a popular area of research in computational biology. Despite the few computational tools employed to address this problem, their resulting performance still requires improvements. In this study, we treat enhancers by the word embeddings, including sub-word information of its biological words, which then serve as features to be fed into a support vector machine algorithm to classify them. We present iEnhancer-5Step, a web server containing two-layer classifiers to identify enhancers and their strength. We are able to attain an independent test accuracy of 79% and 63.5% in the two layers, respectively. Compared to current predictors on the same dataset, our proposed method is able to yield superior performance as compared to the other methods. Moreover, this study provides a basis for further research that can enrich the field of applying natural language processing techniques in biological sequences. iEnhancer-5Step is freely accessible via http://biologydeep.com/fastenc/.

Computational identification of vesicular transport proteins from sequences using deep gated recurrent units architecture.

Protein function prediction is one of the most well-studied topics, attracting attention from countless researchers in the field of computational biology. Implementing deep neural networks that help improve the prediction of protein function, however, is still a major challenge. In this research, we suggested a new strategy that includes gated recurrent units and position-specific scoring matrix profiles to predict vesicular transportation proteins, a biological function of great importance. Although it is difficult to discover its function, our model is able to achieve accuracies of 82.3% and 85.8% in the cross-validation and independent dataset, respectively. We also solve the problem of imbalance in the dataset via tuning class weight in the deep learning model. The results generated showed sensitivity, specificity, MCC, and AUC to have values of 79.2%, 82.9%, 0.52, and 0.861, respectively. Our strategy shows superiority in results on the same dataset against all other state-of-the-art algorithms. In our suggested research, we have suggested a technique for the discovery of more proteins, particularly proteins connected with vesicular transport. In addition, our accomplishment could encourage the use of gated recurrent units architecture in protein function prediction.