SRNARFTarget: a fast machine-learning-based approach for transcriptome-wide sRNA target prediction.
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ABSTRACT:
SUBMITTER: Naskulwar K
PROVIDER: S-EPMC8794260 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The identification of drug/compound-target interactions (DTIs) constitutes the basis of drug discovery, for which computational predictive approaches have been developed. As a relatively new data-driven paradigm, proteochemometric (PCM) modeling utilizes both protein and compound properties as a pair at the input level and processes them via statistical/machine learning. The representation of input samples (i.e., proteins and their ligands) in the form of quantitative feature vectors is crucial for the extraction of interaction-related properties during the artificial learning and subsequent prediction of DTIs. Lately, the representation learning approach, in which input samples are automatically featurized via training and applying a machine/deep learning model, has been utilized in biomedical sciences. In this study, we performed a comprehensive investigation of different computational approaches/techniques for protein featurization (including both conventional approaches and the novel learned embeddings), data preparation and exploration, machine learning-based modeling, and performance evaluation with the aim of achieving better data representations and more successful learning in DTI prediction. For this, we first constructed realistic and challenging benchmark datasets on small, medium, and large scales to be used as reliable gold standards for specific DTI modeling tasks. We developed and applied a network analysis-based splitting strategy to divide datasets into structurally different training and test folds. Using these datasets together with various featurization methods, we trained and tested DTI prediction models and evaluated their performance from different angles. Our main findings can be summarized under 3 items: (i) random splitting of datasets into train and test folds leads to near-complete data memorization and produce highly over-optimistic results, as a result, should be avoided, (ii) learned protein sequence embeddings work well in DTI prediction and offer high potential, despite interaction-related properties (e.g., structures) of proteins are unused during their self-supervised model training, and (iii) during the learning process, PCM models tend to rely heavily on compound features while partially ignoring protein features, primarily due to the inherent bias in DTI data, indicating the requirement for new and unbiased datasets. We hope this study will aid researchers in designing robust and high-performing data-driven DTI prediction systems that have real-world translational value in drug discovery.
| S-EPMC9901167 | biostudies-literature
Project description:Bacterial genomes encode a plethora of small RNAs (sRNAs), which are heterogeneous in size, structure and function. Most sRNAs act as post-transcriptional regulators by means of specific base pairing interactions with the 5'-untranslated region of mRNA transcripts, thereby modifying the stability of the target transcript and/or its ability to be translated. Here, we present RNApredator, a web server for the prediction of sRNA targets. The user can choose from a set of over 2155 genomes and plasmids from 1183 bacterial species. RNApredator then uses a dynamic programming approach, RNAplex, to compute putative targets. Compared to web servers with a similar task, RNApredator takes the accessibility of the target during the target search into account, improving the specificity of the predictions. Furthermore, enrichment in Gene Ontology terms, cellular pathways as well as changes in accessibilities along the target sequence can be done in fully automated post-processing steps. The predictive performance of the underlying dynamic programming approach RNAplex is similar to that of more complex methods, but needs at least three orders of magnitude less time to complete. RNApredator is available at http://rna.tbi.univie.ac.at/RNApredator.
| S-EPMC3125805 | biostudies-literature
Project description:BackgroundVirtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites.ResultsWe developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms.ConclusionOnly a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila, suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org.
| S-EPMC2889937 | biostudies-literature
Project description:Since the last published update in 2014, the SuperPred webserver has been continuously developed to offer state-of-the-art models for drug classification according to ATC classes and target prediction. For the first time, a thoroughly filtered ATC dataset, that is suitable for accurate predictions, is provided along with detailed information on the achieved predictions. This aims to overcome the challenges in comparing different published prediction methods, since performance can vary greatly depending on the training dataset used. Additionally, both ATC and target prediction have been reworked and are now based on machine learning models instead of overall structural similarity, stressing the importance of functional groups for the mechanism of action of small molecule substances. Additionally, the dataset for the target prediction has been extensively filtered and is no longer only based on confirmed binders but also includes non-binding substances to reduce false positives. Using these methods, accuracy for the ATC prediction could be increased by almost 5% to 80.5% compared to the previous version, and additionally the scoring function now offers values which are easily assessable at first glance. SuperPred 3.0 is publicly available without the need for registration at: https://prediction.charite.de/index.php.
| S-EPMC9252837 | biostudies-literature
Project description:Machine learning (ML) is poised as a transformational approach uniquely positioned to discover the hidden biological interactions for better prediction and diagnosis of complex diseases. In this work, we integrated ML-based models for feature selection and classification to quantify the risk of individual susceptibility to asthma using single nucleotide polymorphism (SNP). Random forest (RF) and recursive feature elimination (RFE) algorithm were implemented to identify the SNPs with high implication to asthma. K-nearest neighbor (kNN) and support vector machine (SVM) algorithms were trained to classify the identified SNPs whether associated with non-asthmatic or asthmatic samples. Feature selection step showed that RF outperformed RFE and the feature importance score derived from RF was consistently high for a subset of SNPs, indicating the robustness of RF in selecting relevant features associated with asthma. Model comparison showed that the integration of RF-SVM obtained the highest model performance with an accuracy, precision, and sensitivity of 62.5%, 65.3%, and 69%, respectively, when compared to the baseline, RF-kNN, and an external MeanDiff-kNN models. Furthermore, results show that the occurrence of asthma can be predicted with an Area under the Curve (AUC) of 0.62 and 0.64 for RF-SVM and RF-kNN models, respectively. This study demonstrates the integration of ML models to augment traditional methods in predicting genetic predisposition to multifactorial diseases such as asthma.
| S-EPMC6892549 | biostudies-literature
Project description:Gene expression profiles were generated from 199 primary breast cancer patients. Samples 1-176 were used in another study, GEO Series GSE22820, and form the training data set in this study. Sample numbers 200-222 form a validation set. This data is used to model a machine learning classifier for Estrogen Receptor Status. RNA was isolated from 199 primary breast cancer patients. A machine learning classifier was built to predict ER status using only three gene features.
2013-01-01 | E-GEOD-29210 | biostudies-arrayexpress
Project description:The prediction of antimicrobial resistance (AMR) based on genomic information can improve patient outcomes. Genetic mechanisms have been shown to explain AMR with accuracies in line with standard microbiology laboratory testing. To translate genetic mechanisms into phenotypic AMR, machine learning has been successfully applied. AMR machine learning models typically use nucleotide k-mer counts to represent genomic sequences. While k-mer representation efficiently captures sequence variation, it also results in high-dimensional and sparse data. With limited training data available, achieving acceptable model performance or model interpretability is challenging. In this study, we explore the utility of feature engineering with several biologically relevant signals. We propose to predict the functional impact of observed mutations with PROVEAN to use the predicted impact as a new feature for each protein in an organism's proteome. The addition of the new features was tested on a total of 19,521 isolates across nine clinically relevant pathogens and 30 different antibiotics. The new features significantly improved the predictive performance of trained AMR models for Pseudomonas aeruginosa, Citrobacter freundii, and Escherichia coli. The balanced accuracy of the respective models of those three pathogens improved by 6.0% on average.
| S-EPMC8657983 | biostudies-literature
Project description:We hypothesized that blood lactate concentration([Lac]blood) is a function of cardiopulmonary variables, exercise intensity and some anthropometric elements during aerobic exercise. This investigation aimed to establish a mathematical model to estimate [Lac]blood noninvasively during constant work rate (CWR) exercise of various intensities. 31 healthy participants were recruited and each underwent 4 cardiopulmonary exercise tests: one incremental and three CWR tests (low: 35% of peak work rate for 15?min, moderate: 60% 10?min and high: 90% 4?min). At the end of each CWR test, venous blood was sampled to determine [Lac]blood. 31 trios of CWR tests were employed to construct the mathematical model, which utilized exponential regression combined with Taylor expansion. Good fitting was achieved when the conditions of low and moderate intensity were put in one model; high-intensity in another. Standard deviation of fitting error in the former condition is 0.52; in the latter is 1.82?mmol/liter. Weighting analysis demonstrated that, besides heart rate, respiratory variables are required in the estimation of [Lac]blood in the model of low/moderate intensity. In conclusion, by measuring noninvasive cardio-respiratory parameters, [Lac]blood during CWR exercise can be determined with good accuracy. This should have application in endurance training and future exercise industry.
| S-EPMC6379358 | biostudies-literature
Project description:Accurate protein side-chain conformation prediction is crucial for protein modeling and existing methods for the task are widely used; however, faster and more accurate methods are still required. Here we present a new machine learning approach to the problem where an energy function for each rotamer in a structure is computed additively over pairs of contacting atoms. A family of 156 neural networks indexed by amino acid and contacting atom types is used to compute these rotamer energies as a function of atomic contact distances. Although direct energy targets are not available for training, the neural networks can still be optimized by converting the energies to probabilities and optimizing these probabilities using Markov Chain Monte Carlo methods. The resulting predictor SIDEpro makes predictions by initially setting the rotamer probabilities for each residue from a backbone-dependent rotamer library, then iteratively updating these probabilities using the trained neural networks. After convergences of the probabilities, the side-chains are set to the highest probability rotamer. Finally, a post processing clash reduction step is applied to the models. SIDEpro represents a significant improvement in speed and a modest, but statistically significant, improvement in accuracy when compared with the state-of-the-art for rapid side-chain prediction method SCWRL4 on the following datasets: (1) 379 protein test set of SCWRL4; (2) 94 proteins from CASP9; (3) a set of seven large protein-only complexes; and (4) a ribosome with and without the RNA. Using the SCWRL4 test set, SIDEpro's accuracy (χ(1) 86.14%, χ(1+2) 74.15%) is slightly better than SCWRL4-FRM (χ(1) 85.43%, χ(1+2) 73.47%) and it is 7.0 times faster. On the same test set SIDEpro is clearly more accurate than SCWRL4-rigid rotamer model (RRM) (χ(1) 84.15%, χ(1+2) 71.24%) and 2.4 times faster. Evaluation on the additional test sets yield similar accuracy results with SIDEpro being slightly more accurate than SCWRL4-flexible rotamer model (FRM) and clearly more accurate than SCWRL4-RRM; however, the gap in CPU time is much more significant when the methods are applied to large protein complexes. SIDEpro is part of the SCRATCH suite of predictors and available from: http://scratch.proteomics.ics.uci.edu/.
| S-EPMC3240718 | biostudies-literature
Project description:BackgroundThe genome-wide identification of both morbid genes, i.e., those genes whose mutations cause hereditary human diseases, and druggable genes, i.e., genes coding for proteins whose modulation by small molecules elicits phenotypic effects, requires experimental approaches that are time-consuming and laborious. Thus, a computational approach which could accurately predict such genes on a genome-wide scale would be invaluable for accelerating the pace of discovery of causal relationships between genes and diseases as well as the determination of druggability of gene products.ResultsIn this paper we propose a machine learning-based computational approach to predict morbid and druggable genes on a genome-wide scale. For this purpose, we constructed a decision tree-based meta-classifier and trained it on datasets containing, for each morbid and druggable gene, network topological features, tissue expression profile and subcellular localization data as learning attributes. This meta-classifier correctly recovered 65% of known morbid genes with a precision of 66% and correctly recovered 78% of known druggable genes with a precision of 75%. It was than used to assign morbidity and druggability scores to genes not known to be morbid and druggable and we showed a good match between these scores and literature data. Finally, we generated decision trees by training the J48 algorithm on the morbidity and druggability datasets to discover cellular rules for morbidity and druggability and, among the rules, we found that the number of regulating transcription factors and plasma membrane localization are the most important factors to morbidity and druggability, respectively.ConclusionsWe were able to demonstrate that network topological features along with tissue expression profile and subcellular localization can reliably predict human morbid and druggable genes on a genome-wide scale. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing morbidity and druggability.
| S-EPMC3045802 | biostudies-literature