Dataset Information

DIRECTION: a machine learning framework for predicting and characterizing DNA methylation and hydroxymethylation in mammalian genomes.

ABSTRACT: Motivation:5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major epigenetic modifications known to significantly alter mammalian gene expression. High-throughput assays to detect these modifications are expensive, labor-intensive, unfeasible in some contexts and leave a portion of the genome unqueried. Hence, we devised a novel, supervised, integrative learning framework to perform whole-genome methylation and hydroxymethylation predictions in CpG dinucleotides. Our framework can also perform imputation of missing or low quality data in existing sequencing datasets. Additionally, we developed infrastructure to perform in silico, high-throughput hypotheses testing on such predicted methylation or hydroxymethylation maps. Results:We test our approach on H1 human embryonic stem cells and H1-derived neural progenitor cells. Our predictive model is comparable in accuracy to other state-of-the-art DNA methylation prediction algorithms. We are the first to predict hydroxymethylation in silico with high whole-genome accuracy, paving the way for large-scale reconstruction of hydroxymethylation maps in mammalian model systems. We designed a novel, beam-search driven feature selection algorithm to identify the most discriminative predictor variables, and developed a platform for performing integrative analysis and reconstruction of the epigenome. Our toolkit DIRECTION provides predictions at single nucleotide resolution and identifies relevant features based on resource availability. This offers enhanced biological interpretability of results potentially leading to a better understanding of epigenetic gene regulation. Availability and implementation:http://www.pradiptaray.com/direction, under CC-by-SA license. Contacts:pradiptaray@gmail.com or mchen@utdallas.edu or michael.zhang@utdallas.edu. Supplementary information:Supplementary data are available at Bioinformatics online.

SUBMITTER: Pavlovic M

PROVIDER: S-EPMC5870843 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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DIRECTION: a machine learning framework for predicting and characterizing DNA methylation and hydroxymethylation in mammalian genomes.

Pavlovic Milos M Ray Pradipta P Pavlovic Kristina K Kotamarti Aaron A Chen Min M Zhang Michael Q MQ

Bioinformatics (Oxford, England) 20171001 19

<h4>Motivation</h4>5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major epigenetic modifications known to significantly alter mammalian gene expression. High-throughput assays to detect these modifications are expensive, labor-intensive, unfeasible in some contexts and leave a portion of the genome unqueried. Hence, we devised a novel, supervised, integrative learning framework to perform whole-genome methylation and hydroxymethylation predictions in CpG dinucleotides. Our framework can ...[more]

PMID: 28505334

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Project description:BackgroundThe topology of metabolic networks is both well-studied and remarkably well-conserved across many species. The regulation of these networks, however, is much more poorly characterized, though it is known to be divergent across organisms-two characteristics that make it difficult to model metabolic networks accurately. While many computational methods have been built to unravel transcriptional regulation, there have been few approaches developed for systems-scale analysis and study of metabolic regulation. Here, we present a stepwise machine learning framework that applies established algorithms to identify regulatory interactions in metabolic systems based on metabolic data: stepwise classification of unknown regulation, or SCOUR.ResultsWe evaluated our framework on both noiseless and noisy data, using several models of varying sizes and topologies to show that our approach is generalizable. We found that, when testing on data under the most realistic conditions (low sampling frequency and high noise), SCOUR could identify reaction fluxes controlled only by the concentration of a single metabolite (its primary substrate) with high accuracy. The positive predictive value (PPV) for identifying reactions controlled by the concentration of two metabolites ranged from 32 to 88% for noiseless data, 9.2 to 49% for either low sampling frequency/low noise or high sampling frequency/high noise data, and 6.6-27% for low sampling frequency/high noise data, with results typically sufficiently high for lab validation to be a practical endeavor. While the PPVs for reactions controlled by three metabolites were lower, they were still in most cases significantly better than random classification.ConclusionsSCOUR uses a novel approach to synthetically generate the training data needed to identify regulators of reaction fluxes in a given metabolic system, enabling metabolomics and fluxomics data to be leveraged for regulatory structure inference. By identifying and triaging the most likely candidate regulatory interactions, SCOUR can drastically reduce the amount of time needed to identify and experimentally validate metabolic regulatory interactions. As high-throughput experimental methods for testing these interactions are further developed, SCOUR will provide critical impact in the development of predictive metabolic models in new organisms and pathways.

Project description:BackgroundNo-show to medical appointments has significant adverse effects on healthcare systems and their clients. Using machine learning to predict no-shows allows managers to implement strategies such as overbooking and reminders targeting patients most likely to miss appointments, optimizing the use of resources.MethodsIn this study, we proposed a detailed analytical framework for predicting no-shows while addressing imbalanced datasets. The framework includes a novel use of z-fold cross-validation performed twice during the modeling process to improve model robustness and generalization. We also introduce Symbolic Regression (SR) as a classification algorithm and Instance Hardness Threshold (IHT) as a resampling technique and compared their performance with that of other classification algorithms, such as K-Nearest Neighbors (KNN) and Support Vector Machine (SVM), and resampling techniques, such as Random under Sampling (RUS), Synthetic Minority Oversampling Technique (SMOTE) and NearMiss-1. We validated the framework using two attendance datasets from Brazilian hospitals with no-show rates of 6.65% and 19.03%.ResultsFrom the academic perspective, our study is the first to propose using SR and IHT to predict the no-show of patients. Our findings indicate that SR and IHT presented superior performances compared to other techniques, particularly IHT, which excelled when combined with all classification algorithms and led to low variability in performance metrics results. Our results also outperformed sensitivity outcomes reported in the literature, with values above 0.94 for both datasets.ConclusionThis is the first study to use SR and IHT methods to predict patient no-shows and the first to propose performing z-fold cross-validation twice. Our study highlights the importance of avoiding relying on few validation runs for imbalanced datasets as it may lead to biased results and inadequate analysis of the generalization and stability of the models obtained during the training stage.

Dataset Information

DIRECTION: a machine learning framework for predicting and characterizing DNA methylation and hydroxymethylation in mammalian genomes.

Publications

DIRECTION: a machine learning framework for predicting and characterizing DNA methylation and hydroxymethylation in mammalian genomes.

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