Biomarker identification by reversing the learning mechanism of an autoencoder and recursive feature elimination.

RNA-Seq has made significant contributions to various fields, particularly in cancer research. Recent studies on differential gene expression analysis and the discovery of novel cancer biomarkers have extensively used RNA-Seq data. New biomarker identification is essential for moving cancer research forward, and early cancer diagnosis improves patients' chances of recovery and increases life expectancy. There is an urgency and scope of improvement in both sections. In this paper, we developed an autoencoder-based biomarker identification method by reversing the learning mechanism of the trained encoders. We devised an explainable post hoc methodology for identifying influential genes with a high likelihood of becoming biomarkers. We applied recursive feature elimination to shorten the list further and presented a list of 17 potential biomarkers that are 99.93% accurate in identifying cancer types using support vector machine for the UCI gene expression cancer RNA-Seq dataset consisting of five cancerous tumor types. Our methodology outperforms all of the state-of-the-art methods, confirming the potential of the newly identified biomarkers as well as the efficacy of the biomarker identification procedure. Moreover, we have evaluated the performance of our methodology using six independent RNA-Seq gene expression datasets for several tasks, i.e., classification of tumors from non-tumors, detecting the origin of circulating tumor cells (CTCs), and predicting if metastasis occurs or not. Our methodology achieved stimulating results for these tasks as well. The source code of this project is available at https://github.com/fuad021/biomarker-identification.

Computational identification of multiple lysine PTM sites by analyzing the instance hardness and feature importance.

Identification of post-translational modifications (PTM) is significant in the study of computational proteomics, cell biology, pathogenesis, and drug development due to its role in many bio-molecular mechanisms. Though there are several computational tools to identify individual PTMs, only three predictors have been established to predict multiple PTMs at the same lysine residue. Furthermore, detailed analysis and assessment on dataset balancing and the significance of different feature encoding techniques for a suitable multi-PTM prediction model are still lacking. This study introduces a computational method named 'iMul-kSite' for predicting acetylation, crotonylation, methylation, succinylation, and glutarylation, from an unrecognized peptide sample with one, multiple, or no modifications. After successfully eliminating the redundant data samples from the majority class by analyzing the hardness of the sequence-coupling information, feature representation has been optimized by adopting the combination of ANOVA F-Test and incremental feature selection approach. The proposed predictor predicts multi-label PTM sites with 92.83% accuracy using the top 100 features. It has also achieved a 93.36% aiming rate and 96.23% coverage rate, which are much better than the existing state-of-the-art predictors on the validation test. This performance indicates that 'iMul-kSite' can be used as a supportive tool for further K-PTM study. For the convenience of the experimental scientists, 'iMul-kSite' has been deployed as a user-friendly web-server at http://103.99.176.239/iMul-kSite .

Accurately Predicting Glutarylation Sites Using Sequential Bi-Peptide-Based Evolutionary Features.

Post Translational Modification (PTM) is defined as the alteration of protein sequence upon interaction with different macromolecules after the translation process. Glutarylation is considered one of the most important PTMs, which is associated with a wide range of cellular functioning, including metabolism, translation, and specified separate subcellular localizations. During the past few years, a wide range of computational approaches has been proposed to predict Glutarylation sites. However, despite all the efforts that have been made so far, the prediction performance of the Glutarylation sites has remained limited. One of the main challenges to tackle this problem is to extract features with significant discriminatory information. To address this issue, we propose a new machine learning method called BiPepGlut using the concept of a bi-peptide-based evolutionary method for feature extraction. To build this model, we also use the Extra-Trees (ET) classifier for the classification purpose, which, to the best of our knowledge, has never been used for this task. Our results demonstrate BiPepGlut is able to significantly outperform previously proposed models to tackle this problem. BiPepGlut achieves 92.0%, 84.8%, 95.6%, 0.82, and 0.88 in accuracy, sensitivity, specificity, Matthew's Correlation Coefficient, and F1-score, respectively. BiPepGlut is implemented as a publicly available online predictor.