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The dynamic evolution of the severe acute respiratory syndrome coronavirus 2 virus is primarily driven by mutations in its genetic sequence, culminating in the emergence of variants with increased capability to evade host immune responses. Accurate prediction of such mutations is fundamental in mitigating pandemic spread and developing effective control measures. This study introduces a robust and interpretable deep-learning approach called PRIEST. This innovative model leverages time-series viral sequences to foresee potential viral mutations. Our comprehensive experimental evaluations underscore PRIEST's proficiency in accurately predicting immune-evading mutations. Our work represents a substantial step in utilizing deep-learning methodologies for anticipatory viral mutation analysis and pandemic response. [ABSTRACT FROM AUTHOR]

CRISPR Cas-9 is a groundbreaking genome-editing tool that harnesses bacterial defense systems to alter DNA sequences accurately. This innovative technology holds vast promise in multiple domains like biotechnology, agriculture and medicine. However, such power does not come without its own peril, and one such issue is the potential for unintended modifications (Off-Target), which highlights the need for accurate prediction and mitigation strategies. Though previous studies have demonstrated improvement in Off-Target prediction capability with the application of deep learning, they often struggle with the precision-recall trade-off, limiting their effectiveness and do not provide proper interpretation of the complex decision-making process of their models. To address these limitations, we have thoroughly explored deep learning networks, particularly the recurrent neural network based models, leveraging their established success in handling sequence data. Furthermore, we have employed genetic algorithm for hyperparameter tuning to optimize these models' performance. The results from our experiments demonstrate significant performance improvement compared with the current state-of-the-art in Off-Target prediction, highlighting the efficacy of our approach. Furthermore, leveraging the power of the integrated gradient method, we make an effort to interpret our models resulting in a detailed analysis and understanding of the underlying factors that contribute to Off-Target predictions, in particular the presence of two sub-regions in the seed region of single guide RNA which extends the established biological hypothesis of Off-Target effects. To the best of our knowledge, our model can be considered as the first model combining high efficacy, interpretability and a desirable balance between precision and recall. [ABSTRACT FROM AUTHOR]

Lysine succinylation is a kind of post-translational modification (PTM) that plays a crucial role in regulating the cellular processes. Aberrant succinylation may cause inflammation, cancers, metabolism diseases and nervous system diseases. The experimental methods to detect succinylation sites are time-consuming and costly. This thus calls for computational models with high efficacy, and attention has been given in the literature to develop such models, albeit with only moderate success in the context of different evaluation metrics. One crucial aspect in this context is the biochemical and physicochemical properties of amino acids, which appear to be useful as features for such computational predictors. However, some of the existing computational models did not use the biochemical and physicochemical properties of amino acids. In contrast, some others used them without considering the inter-dependency among the properties. The combinations of biochemical and physicochemical properties derived through our optimization process achieve better results than the results achieved by combining all the properties. We propose three deep learning architectures: CNN+Bi-LSTM (CBL), Bi-LSTM+CNN (BLC) and their combination (CBL_BLC). We find that CBL_BLC outperforms the other two. Ensembling of different models successfully improves the results. Notably, tuning the threshold of the ensemble classifiers further improves the results. Upon comparing our work with other existing works on two datasets, we successfully achieve better sensitivity and specificity by varying the threshold value. [ABSTRACT FROM AUTHOR]

Background Genomic Islands (GIs) are clusters of genes that are mobilized through horizontal gene transfer. GIs play a pivotal role in bacterial evolution as a mechanism of diversification and adaptation to different niches. Therefore, identification and characterization of GIs in bacterial genomes is important for understanding bacterial evolution. However, quantifying GIs is inherently difficult, and the existing methods suffer from low prediction accuracy and precision–recall trade-off. Moreover, several of them are supervised in nature, and thus, their applications to newly sequenced genomes are riddled with their dependency on the functional annotation of existing genomes. Results We present SSG-LUGIA, a completely automated and unsupervised approach for identifying GIs and horizontally transferred genes. SSG-LUGIA is a novel method based on unsupervised anomaly detection technique, accompanied by further refinement using cues from signal processing literature. SSG-LUGIA leverages the atypical compositional biases of the alien genes to localize GIs in prokaryotic genomes. SSG-LUGIA was assessed on a large benchmark dataset 'IslandPick' and on a set of 15 well-studied genomes in the literature and followed by a thorough analysis on the well-understood Salmonella typhi CT18 genome. Furthermore, the efficacy of SSG-LUGIA in identifying horizontally transferred genes was evaluated on two additional bacterial genomes, namely, those of Corynebacterium diphtheria NCTC13129 and Pseudomonas aeruginosa LESB58. SSG-LUGIA was examined on draft genomes and was demonstrated to be efficient as an ensemble method. Conclusions Our results indicate that SSG-LUGIA achieved superior performance in comparison to frequently used existing methods. Importantly, it yielded a better trade-off between precision and recall than the existing methods. Its nondependency on the functional annotation of genomes makes it suitable for analyzing newly sequenced, yet uncharacterized genomes. Thus, our study is a significant advance in identification of GIs and horizontally transferred genes. SSG-LUGIA is available as an open source software at https://nibtehaz.github.io/SSG-LUGIA/. [ABSTRACT FROM AUTHOR]

Despite impressive improvement in the next-generation sequencing technology, reliable detection of indels is still a difficult endeavour. Recognition of true indels is of prime importance in many applications, such as personalized health care, disease genomics and population genetics. Recently, advanced machine learning techniques have been successfully applied to classification problems with large-scale data. In this paper, we present SICaRiO, a gradient boosting classifier for the reliable detection of true indels, trained with the gold-standard dataset from 'Genome in a Bottle' (GIAB) consortium. Our filtering scheme significantly improves the performance of each variant calling pipeline used in GIAB and beyond. SICaRiO uses genomic features that can be computed from publicly available resources, i.e. it does not require sequencing pipeline-specific information (e.g. read depth). This study also sheds lights on prior genomic contexts responsible for the erroneous calling of indels made by sequencing pipelines. We have compared prediction difficulty for three categories of indels over different sequencing pipelines. We have also ranked genomic features according to their predictivity in determining false positives. [ABSTRACT FROM AUTHOR]

Motivation Researchers and practitioners use a number of popular sequence comparison tools that use many alignment-based techniques. Due to high time and space complexity and length-related restrictions, researchers often seek alignment-free tools. Recently, some interesting ideas, namely, Minimal Absent Words (MAW) and Relative Absent Words (RAW), have received much interest among the scientific community as distance measures that can give us alignment-free alternatives. This drives us to structure a framework for analysing biological sequences in an alignment-free manner. Results In this application note, we present Alignment-free Dissimilarity Analysis & Comparison Tool (ADACT), a simple web-based tool that computes the analogy among sequences using a varied number of indexes through the distance matrix, species relation list and phylogenetic tree. This tool basically combines absent word (MAW or RAW) computation, dissimilarity measures, species relationship and thus brings all required software in one platform for the ease of researchers and practitioners alike in the field of bioinformatics. We have also developed a restful API. Availability and implementation ADACT has been hosted at http://research.buet.ac.bd/ADACT/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]