The development of robust anomaly-based network detection systems, which are preferred over static signal-based network intrusion, is vital for cybersecurity. The development of a flexible and dynamic security system is required to tackle the new attacks. Current intrusion detection systems (IDSs) suffer to attain both the high detection rate and low false alarm rate. To address this issue, in this paper, we propose an IDS using different machine learning (ML) and deep learning (DL) models. This paper presents a comparative analysis of different ML models and DL models on Coburg intrusion detection datasets (CIDDSs). First, we compare different ML- and DL-based models on the CIDDS dataset. Second, we propose an ensemble model that combines the best ML and DL models to achieve high-performance metrics. Finally, we benchmarked our best models with the CIC-IDS2017 dataset and compared them with state-of-the-art models. While the popular IDS datasets like KDD99 and NSL-KDD fail to represent the recent attacks and suffer from network biases, CIDDS, used in this research, encompasses labeled flow-based data in a simulated office environment with both updated attacks and normal usage. Furthermore, both accuracy and interpretability must be considered while implementing AI models. Both ML and DL models achieved an accuracy of 99% on the CIDDS dataset with a high detection rate, low false alarm rate, and relatively low training costs. Feature importance was also studied using the Classification and regression tree (CART) model. Our models performed well in 10-fold cross-validation and independent testing. CART and convolutional neural network (CNN) with embedding achieved slightly better performance on the CIC-IDS2017 dataset compared to previous models. Together, these results suggest that both ML and DL methods are robust and complementary techniques as an effective network intrusion detection system.

Obtaining an accurate description of protein structure is a fundamental step toward understanding the underpinning of biology. Although recent advances in experimental approaches have greatly enhanced our capabilities to experimentally determine protein structures, the gap between the number of protein sequences and known protein structures is ever increasing. Computational protein structure prediction is one of the ways to fill this gap. Recently, the protein structure prediction field has witnessed a lot of advances due to Deep Learning (DL)-based approaches as evidenced by the success of AlphaFold2 in the most recent Critical Assessment of protein Structure Prediction (CASP14). In this article, we highlight important milestones and progresses in the field of protein structure prediction due to DL-based methods as observed in CASP experiments. We describe advances in various steps of protein structure prediction pipeline viz. protein contact map prediction, protein distogram prediction, protein real-valued distance prediction, and Quality Assessment/refinement. We also highlight some end-to-end DL-based approaches for protein structure prediction approaches. Additionally, as there have been some recent DL-based advances in protein structure determination using Cryo-Electron (Cryo-EM) microscopy based, we also highlight some of the important progress in the field. Finally, we provide an outlook and possible future research directions for DL-based approaches in the protein structure prediction arena.

Background: Protein succinylation has recently emerged as an important and common post-translation modification (PTM) that occurs on lysine residues. Succinylation is notable both in its size (e.g., at 100 Da, it is one of the larger chemical PTMs) and in its ability to modify the net charge of the modified lysine residue from + 1 to − 1 at physiological pH. The gross local changes that occur in proteins upon succinylation have been shown to correspond with changes in gene activity and to be perturbed by defects in the citric acid cycle. These observations, together with the fact that succinate is generated as a metabolic intermediate during cellular respiration, have led to suggestions that protein succinylation may play a role in the interaction between cellular metabolism and important cellular functions. For instance, succinylation likely represents an important aspect of genomic regulation and repair and may have important consequences in the etiology of a number of disease states. In this study, we developed DeepSuccinylSite, a novel prediction tool that uses deep learning methodology along with embedding to identify succinylation sites in proteins based on their primary structure. Results: Using an independent test set of experimentally identified succinylation sites, our method achieved efficiency scores of 79%, 68.7% and 0.48 for sensitivity, specificity and MCC respectively, with an area under the receiver operator characteristic (ROC) curve of 0.8. In side-by-side comparisons with previously described succinylation predictors, DeepSuccinylSite represents a significant improvement in overall accuracy for prediction of succinylation sites. Conclusion: Together, these results suggest that our method represents a robust and complementary technique for advanced exploration of protein succinylation.

Protein phosphorylation is one of the most widespread regulatory mechanisms in eukaryotes. Over the past decade, phosphorylation site prediction has emerged as an important problem in the field of bioinformatics. Here, we report a new method, termed Random Forest-based Phosphosite predictor 2.0 (RF-Phos 2.0), to predict phosphorylation sites given only the primary amino acid sequence of a protein as input. RF-Phos 2.0, which uses random forest with sequence and structural features, is able to identify putative sites of phosphorylation across many protein families. In side-by-side comparisons based on 10-fold cross validation and an independent dataset, RF-Phos 2.0 compares favorably to other popular mammalian phosphosite prediction methods, such as PhosphoSVM, GPS2.1, and Musite.

Glutarylation, which is a newly identified posttranslational modification that occurs on lysine residues, has recently emerged as an important regulator of several metabolic and mitochondrial processes. However, the specific sites of modification on individual proteins, as well as the extent of glutarylation throughout the proteome, remain largely uncharacterized. Though informative, proteomic approaches based on mass spectrometry can be expensive, technically challenging and time-consuming. Therefore, the ability to predict glutarylation sites from protein primary sequences can complement proteomics analyses and help researchers study the characteristics and functional consequences of glutarylation. To this end, we used Random Forest (RF) machine learning strategies to identify the physiochemical and sequence-based features that correlated most substantially with glutarylation. We then used these features to develop a novel method to predict glutarylation sites from primary amino acid sequences using RF. Based on 10-fold cross-validation, the resulting algorithm, termed ‘RF-GlutarySite’, achieved efficiency scores of 75%, 81%, 68% and 0.50 with respect to accuracy (ACC), sensitivity (SN), specificity (SP) and Matthew's correlation coefficient (MCC), respectively. Likewise, using an independent test set, RF-GlutarySite exhibited ACC, SN, SP and MCC scores of 72%, 73%, 70% and 0.43, respectively. Results using both 10-fold cross validation and an independent test set were on par with or better than those achieved by existing glutarylation site predictors. Notably, RF-GlutarySite achieved the highest SN score among available glutarylation site prediction tools. Consequently, our method has the potential to uncover new glutarylation sites and to facilitate the discovery of relationships between glutarylation and well-known lysine modifications, such as acetylation, methylation and SUMOylation, as well as a number of recently identified lysine modifications, such as malonylation and succinylation.

Methylation, which is one of the most prominent post-translational modifications on proteins, regulates many important cellular functions. Though several model-based methylation site predictors have been reported, all existing methods employ machine learning strategies, such as support vector machines and random forest, to predict sites of methylation based on a set of “hand-selected” features. As a consequence, the subsequent models may be biased toward one set of features. Moreover, due to the large number of features, model development can often be computationally expensive. In this paper, we propose an alternative approach based on deep learning to predict arginine methylation sites. Our model, which we termed DeepRMethylSite, is computationally less expensive than traditional feature-based methods while eliminating potential biases that can arise through features selection. Based on independent testing on our dataset, DeepRMethylSite achieved efficiency scores of 68%, 82% and 0.51 with respect to sensitivity (SN), specificity (SP) and Matthew's correlation coefficient (MCC), respectively. Importantly, in side-by-side comparisons with other state-of-the-art methylation site predictors, our method performs on par or better in all scoring metrics tested.