Project description:BackgroundSubcellular localization of messenger RNA (mRNAs) plays a pivotal role in the regulation of gene expression, cell migration as well as in cellular adaptation. Experiment techniques for pinpointing the subcellular localization of mRNAs are laborious, time-consuming and expensive. Therefore, in silico approaches for this purpose are attaining great attention in the RNA community.MethodsIn this article, we propose MSLP, a machine learning-based method to predict the subcellular localization of mRNA. We propose a novel combination of four types of features representing k-mer, pseudo k-tuple nucleotide composition (PseKNC), physicochemical properties of nucleotides, and 3D representation of sequences based on Z-curve transformation to feed into machine learning algorithm to predict the subcellular localization of mRNAs.ResultsConsidering the combination of the above-mentioned features, ennsemble-based models achieved state-of-the-art results in mRNA subcellular localization prediction tasks for multiple benchmark datasets. We evaluated the performance of our method in ten subcellular locations, covering cytoplasm, nucleus, endoplasmic reticulum (ER), extracellular region (ExR), mitochondria, cytosol, pseudopodium, posterior, exosome, and the ribosome. Ablation study highlighted k-mer and PseKNC to be more dominant than other features for predicting cytoplasm, nucleus, and ER localizations. On the other hand, physicochemical properties and Z-curve based features contributed the most to ExR and mitochondria detection. SHAP-based analysis revealed the relative importance of features to provide better insights into the proposed approach.AvailabilityWe have implemented a Docker container and API for end users to run their sequences on our model. Datasets, the code of API and the Docker are shared for the community in GitHub at: https://github.com/smusleh/MSLP .
Project description:Recent evidences suggest that the localization of mRNAs near the subcellular compartment of the translated proteins is a more robust cellular tool, which optimizes protein expression, post-transcriptionally. Retention of mRNA in the nucleus can regulate the amount of protein translated from each mRNA, thus allowing a tight temporal regulation of translation or buffering of protein levels from bursty transcription. Besides, mRNA localization performs a variety of additional roles like long-distance signaling, facilitating assembly of protein complexes and coordination of developmental processes. Here, we describe a novel machine-learning based tool, mRNALoc, to predict five sub-cellular locations of eukaryotic mRNAs using cDNA/mRNA sequences. During five fold cross-validations, the maximum overall accuracy was 65.19, 75.36, 67.10, 99.70 and 73.59% for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. Assessment on independent datasets revealed the prediction accuracies of 58.10, 69.23, 64.55, 96.88 and 69.35% for extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The corresponding values of AUC were 0.76, 0.75, 0.70, 0.98 and 0.74 for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The mRNALoc standalone software and web-server are freely available for academic use under GNU GPL at http://proteininformatics.org/mkumar/mrnaloc.
Project description:The lncATLAS database quantifies the relative cytoplasmic versus nuclear abundance of long non-coding RNAs (lncRNAs) observed in 15 human cell lines. The literature describes several machine learning models trained and evaluated on these and similar datasets. These reports showed moderate performance, e.g. 72-74% accuracy, on test subsets of the data withheld from training. In all these reports, the datasets were filtered to include genes with extreme values while excluding genes with values in the middle range and the filters were applied prior to partitioning the data into training and testing subsets. Using several models and lncATLAS data, we show that this 'middle exclusion' protocol boosts performance metrics without boosting model performance on unfiltered test data. We show that various models achieve only about 60% accuracy when evaluated on unfiltered lncRNA data. We suggest that the problem of predicting lncRNA subcellular localization from nucleotide sequences is more challenging than currently perceived. We provide a basic model and evaluation procedure as a benchmark for future studies of this problem.
Project description:Different RNAs have distinct subcellular localizations. However, nucleotide features that determine these distinct distributions of lncRNAs and mRNAs have yet to be fully addressed. Here, we develop RNAlight, a machine learning model based on LightGBM, to identify nucleotide k-mers contributing to the subcellular localizations of mRNAs and lncRNAs. With the Tree SHAP algorithm, RNAlight extracts nucleotide features for cytoplasmic or nuclear localization of RNAs, indicating the sequence basis for distinct RNA subcellular localizations. By assembling k-mers to sequence features and subsequently mapping to known RBP-associated motifs, different types of sequence features and their associated RBPs were additionally uncovered for lncRNAs and mRNAs with distinct subcellular localizations. Finally, we extended RNAlight to precisely predict the subcellular localizations of other types of RNAs, including snRNAs, snoRNAs and different circular RNA transcripts, suggesting the generality of using RNAlight for RNA subcellular localization prediction.
Project description:Stem cell organoids are powerful models for studying organ development, disease modeling, drug screening, and regenerative medicine applications. The convergence of organoid technology, tissue engineering, and artificial intelligence (AI) could potentially enhance our understanding of the design principle for organoid engineering. In this study, we utilized micropatterning techniques to create a designer library of 230 cardiac organoids with 7 geometric designs (Circle 200, Circle 600, Circle 1000, Rectangle 1:1, Rectangle 1:4, Star 1:1, and Star 1:4). We employed manifold learning techniques to analyze single organoid heterogeneity based on 10 physiological parameters. We successfully clustered and refined our cardiac organoids based on their functional similarity using unsupervised machine learning approaches, thus elucidating unique functionalities associated with geometric designs. We also highlighted the critical role of calcium rising time in distinguishing organoids based on geometric patterns and clustering results. This innovative integration of organoid engineering and machine learning enhances our understanding of structure-function relationships in cardiac organoids, paving the way for more controlled and optimized organoid design.
Project description:Cochlear implants (CIs) are neuroprosthetics that can provide a sense of sound to people with severe-to-profound hearing loss. A CI contains an electrode array (EA) that is threaded into the cochlea during surgery. Recent studies have shown that hearing outcomes are correlated with EA placement. An image-guided cochlear implant programming technique is based on this correlation and utilizes the EA location with respect to the intracochlear anatomy to help audiologists adjust the CI settings to improve hearing. Automated methods to localize EA in postoperative CT images are of great interest for large-scale studies and for translation into the clinical workflow. In this work, we propose a unified deep-learning-based framework for automated EA localization. It consists of a multi-task network and a series of postprocessing algorithms to localize various types of EAs. The evaluation on a dataset with 27 cadaveric samples shows that its localization error is slightly smaller than the state-of-the-art method. Another evaluation on a large-scale clinical dataset containing 561 cases across two institutions demonstrates a significant improvement in robustness compared to the state-of-the-art method. This suggests that this technique could be integrated into the clinical workflow and provide audiologists with information that facilitates the programming of the implant leading to improved patient care.
Project description:Adenoviruses (AdVs) constitute a diverse family with many pathogenic types that infect a broad range of hosts. Understanding the pathogenesis of adenoviral infections is not only clinically relevant but also important to elucidate the potential use of AdVs as vectors in therapeutic applications. For an adenoviral infection to occur, attachment of the viral ligand to a cellular receptor on the host organism is a prerequisite and, in this sense, it is a criterion to decide whether an adenoviral infection can potentially happen. The interaction between any virus and its corresponding host organism is a specific kind of protein-protein interaction (PPI) and several experimental techniques, including high-throughput methods are being used in exploring such interactions. As a result, there has been accumulating data on virus-host interactions including a significant portion reported at publicly available bioinformatics resources. There is not, however, a computational model to integrate and interpret the existing data to draw out concise decisions, such as whether an infection happens or not. In this study, accepting the cellular entry of AdV as a decisive parameter for infectivity, we have developed a machine learning, more precisely support vector machine (SVM), based methodology to predict whether adenoviral infection can take place in a given host. For this purpose, we used the sequence data of the known receptors of AdVs, we identified sets of adenoviral ligands and their respective host species, and eventually, we have constructed a comprehensive adenovirus-host interaction dataset. Then, we committed interaction predictions through publicly available virus-host PPI tools and constructed an AdV infection predictor model using SVM with RBF kernel, with the overall sensitivity, specificity, and AUC of 0.88 ± 0.011, 0.83 ± 0.064, and 0.86 ± 0.030, respectively. ML-AdVInfect is the first of its kind as an effective predictor to screen the infection capacity along with anticipating any cross-species shifts. We anticipate our approach led to ML-AdVInfect can be adapted in making predictions for other viral infections.
Project description:Translation of ribosomal protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms that modulate RP-mRNA translation in coordination with other cellular processes are poorly defined. Here, we show that subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to the actin-rich cell protrusions. This localization is mediated by La-related protein 6 (LARP6), an RNA-binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, enhancing RP synthesis, ribosome biogenesis, and the overall protein synthesis in migratory cells. In human breast carcinomas, epithelial-to-mesenchymal transition (EMT) upregulates LARP6 expression to enhance protein synthesis and support invasive growth. Our findings reveal LARP6-mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration and demonstrate a role for this process in cancer progression downstream of EMT.
Project description:A crucial part of sentiment classification is featuring extraction because it involves extracting valuable information from text data, which affects the model's performance. The goal of this paper is to help in selecting a suitable feature extraction method to enhance the performance of sentiment analysis tasks. In order to provide directions for future machine learning and feature extraction research, it is important to analyze and summarize feature extraction techniques methodically from a machine learning standpoint. There are several methods under consideration, including Bag-of-words (BOW), Word2Vector, N-gram, Term Frequency- Inverse Document Frequency (TF-IDF), Hashing Vectorizer (HV), and Global vector for word representation (GloVe). To prove the ability of each feature extractor, we applied it to the Twitter US airlines and Amazon musical instrument reviews datasets. Finally, we trained a random forest classifier using 70% of the training data and 30% of the testing data, enabling us to evaluate and compare the performance using different metrics. Based on our results, we find that the TD-IDF technique demonstrates superior performance, with an accuracy of 99% in the Amazon reviews dataset and 96% in the Twitter US airlines dataset. This study underscores the paramount significance of feature extraction in sentiment analysis, endowing pragmatic insights to elevate model performance and steer future research pursuits.
Project description:Security vulnerabilities play a vital role in network security system. Fuzzing technology is widely used as a vulnerability discovery technology to reduce damage in advance. However, traditional fuzz testing faces many challenges, such as how to mutate input seed files, how to increase code coverage, and how to bypass the format verification effectively. Therefore machine learning techniques have been introduced as a new method into fuzz testing to alleviate these challenges. This paper reviews the research progress of using machine learning techniques for fuzz testing in recent years, analyzes how machine learning improves the fuzzing process and results, and sheds light on future work in fuzzing. Firstly, this paper discusses the reasons why machine learning techniques can be used for fuzzing scenarios and identifies five different stages in which machine learning has been used. Then this paper systematically studies machine learning-based fuzzing models from five dimensions of selection of machine learning algorithms, pre-processing methods, datasets, evaluation metrics, and hyperparameters setting. Secondly, this paper assesses the performance of the machine learning techniques in existing research for fuzz testing. The results of the evaluation prove that machine learning techniques have an acceptable capability of prediction for fuzzing. Finally, the capability of discovering vulnerabilities both traditional fuzzers and machine learning-based fuzzers is analyzed. The results depict that the introduction of machine learning techniques can improve the performance of fuzzing. We hope to provide researchers with a systematic and more in-depth understanding of fuzzing based on machine learning techniques and provide some references for this field through analysis and summarization of multiple dimensions.