Biology subjects

Garmire, L.

Publications and source records attributed to Garmire, L..

8 recordsLinked to original sources

bioRxiv2018

GranatumX: A community engaging and flexible software environment for single-cell analysis

We present GranatumX, a next-generation software environment for single-cell data analysis. GranatumX is inspired by the interactive web tool Granatum. It enables biologists to access the latest single-cell bioinformatics methods in a web-based graphical environment. It also offers software developers the opportunity to rapidly promote their own tools with others in customizable pipelines. The architecture of GranatumX allows for easy inclusion of plugin modules, named Gboxes, that wrap around bioinformatics tools written in various programming languages and on various platforms. GranatumX can be run on the cloud or private servers and generate reproducible results. It is a community-engaging, flexible, and evolving software ecosystem for scRNA-Seq analysis, connecting developers with bench scientists. GranatumX is freely accessible at http://garmiregroup.org/granatumx/app.

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bioRxiv2018

DeepImpute: an accurate, fast and scalable deep neural network method to impute single-cell RNA-Seq data

BackgroundSingle-cell RNA sequencing (scRNA-seq) offers new opportunities to study gene expression of tens of thousands of single cells simultaneously. However, a significant problem of current scRNA-seq data is the large fractions of missing values or \"dropouts\" in gene counts. Incorrect handling of dropouts may affect downstream bioinformatics analysis. As the number of scRNA-seq datasets grows drastically, it is crucial to have accurate and efficient imputation methods to handle these dropouts.\n\nMethodsWe present DeepImpute, a deep neural network based imputation algorithm. The architecture of DeepImpute efficiently uses dropout layers and loss functions to learn patterns in the data, allowing for accurate imputation.\n\nResultsOverall DeepImpute yields better accuracy than other publicly available scRNA-Seq imputation methods on experimental data, as measured by mean squared error or Pearsons correlation coefficient. Moreover, its efficient implementation provides significantly higher performance over the other methods as dataset size increases. Additionally, as a machine learning method, DeepImpute allows to use a subset of data to train the model and save even more computing time, without much sacrifice on the prediction accuracy.\n\nConclusionsDeepImpute is an accurate, fast and scalable imputation tool that is suited to handle the ever increasing volume of scRNA-seq data. The package is freely available at https://github.com/lanagarmire/DeepImpute

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bioRxiv2018

Lilikoi: an R package for personalized pathway-based classification modeling using metabolomics data

Lilikoi (Hawaiian word for passion fruit) is a new and comprehensive R package for personalized pathway based classification modelling, using metabolomics data. Four basic modules are presented as the backbone of the package: 1) Feature mapping module, which standardizes the metabolite names provided by users, and map them to pathways. 2) Dimension transformation module, which transforms the metabolomic profiles to personalized pathway-based profiles using pathway deregulation scores (PDS). 3) Feature selection module which helps to select the significant pathway features related to the disease phenotypes, and 4) Classification and prediction module which offers various machine-learning classification algorithms. The package is freely available under the GPLv3 license through the github repository at: https://github.com/lanagarmire/lilikoi

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bioRxiv2018

Metabolomics profile of umbilical cord blood is associated with maternal pre-pregnant obesity in a prospective multi-ethnic cohort displaying health disparities

Maternal obesity has become a growing global health concern that may predispose the offspring to medical conditions later in life. However, the metabolic link between maternal pre-pregnant obesity and healthy offspring has not yet been fully elucidated. In this study, we conducted a case-control study using coupled untargeted and targeted metabolomics approach, from the newborn cord blood metabolomes associated with a matched maternal pre-pregnant obesity cohort of 28 cases and 29 controls. The subjects were recruited from multi-ethnic populations in Hawaii, including rarely reported Native Hawaiian and other Pacific Islanders (NHPI). We found that maternal obesity was the most important factor contributing to differences in cord blood metabolomics. Using elastic net regularization based logistic regression model, we identified 29 metabolites as potential early-life biomarkers manifesting intrauterine effect of maternal obesity, with accuracy as high as 0.947 after adjusting for clinical confounding (maternal and paternal age and ethnicity, parity and gravidity). We validated the model results in a subsequent set of samples (N=30) with an accuracy of 0.822. Among the metabolites, six metabolites (galactonic acid, butenylcarnitine, 2-hydroxy-3-methylbutyric acid, phosphatidylcholine diacyl C40:3, 1,5-anhydrosorbitol, and phosphatidylcholine acyl-alkyl 40:3) were individually and significantly different between the maternal obese vs. norm-weight groups. Interestingly, Hydroxy-3-methylbutyric acid showed significnatly higher levels in cord blood from the NHPI group, compared to asian and caucasian groups. In summary, significant associations were observed between maternal pre-pregnant obesity and offspring metabolomics alternation at birth, revealing the inter-generational impact of maternal obesity.

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bioRxiv2017

Deep learning accurately predicts estrogen receptor status in breast cancer metabolomics data

Metabolomics holds the promise as a new technology to diagnose highly heterogeneous diseases. Conventionally, metabolomics data analysis for diagnosis is done using various statistical and machine learning based classification methods. However, it remains unknown if deep neural network, a class of increasingly popular machine learning methods, is suitable to classify metabolomics data. Here we use a cohort of 271 breast cancer tissues, 204 positive estrogen receptor (ER+) and 67 negative estrogen receptor (ER-), to test the accuracies of autoencoder, a deep learning (DL) framework, as well as six widely used machine learning models, namely Random Forest (RF), Support Vector Machines (SVM), Recursive Partitioning and Regression Trees (RPART), Linear Discriminant Analysis (LDA), Prediction Analysis for Microarrays (PAM), and Generalized Boosted Models (GBM). DL framework has the highest area under the curve (AUC) of 0.93 in classifying ER+/ER-patients, compared to the other six machine learning algorithms. Furthermore, the biological interpretation of the first hidden layer reveals eight commonly enriched significant metabolomics pathways (adjusted P-value<0.05) that cannot be discovered by other machine learning methods. Among them, protein digestion & absorption and ATP-binding cassette (ABC) transporters pathways are also confirmed in integrated analysis between metabolomics and gene expression data in these samples. In summary, deep learning method shows advantages for metabolomics based breast cancer ER status classification, with both the highest prediction accurcy (AUC=0.93) and better revelation of disease biology. We encourage the adoption of autoencoder based deep learning method in the metabolomics research community for classification.

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bioRxiv2017

Deep Learning based multi-omics integration robustly predicts survival in liver cancer

Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill in this gap, we present a deep learning (DL) based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We build the DL based, survival-sensitive model on 360 HCC patients data using RNA-seq, miRNA-seq and methylation data from TCGA, which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL based model provides two optimal subgroups of patients with significant survival differences (P=7.13e-6) and good model fitness (C-index=0.68). More aggressive subtype is associated with frequent TP53 inactivation mutations, higher expression of stemness markers (KRT19, EPCAM) and tumor marker BIRC5, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (n=230, C-index=0.75), NCI cohort (n=221, C-index=0.67), Chinese cohort (n=166, C-index=0.69), E-TABM-36 cohort (n=40, C-index=0.77), and Hawaiian cohort (n=27, C-index=0.82). This is the first study to employ deep learning to identify multi-omics features linked to the differential survival of HCC patients. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction.

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bioRxiv2017

Granatum: a graphical single-cell RNA-seq analysis pipeline for genomics scientists

BackgroundSingle-cell RNA sequencing (scRNA-Seq) is an increasingly popular platform to study heterogeneity at the single-cell level.\n\nComputational methods to process scRNA-Seq have limited accessibility to bench scientists as they require significant amounts of bioinformatics skills.\n\nResultsWe have developed Granatum, a web-based scRNA-Seq analysis pipeline to make analysis more broadly accessible to researchers. Without a single line of programming code, users can click through the pipeline, setting parameters and visualizing results via the interactive graphical interface Granatum conveniently walks users through various steps of scRNA-Seq analysis. It has a comprehensive list of modules, including plate merging and batch-effect removal, outlier-sample removal, gene filtering, geneexpression normalization, cell clustering, differential gene expression analysis, pathway/ontology enrichment analysis, protein-networ interaction visualization, and pseudo-time cell series construction.\n\nConclusionsGranatum enables broad adoption of scRNA-Seq technology by empowering the bench scientists with an easy-to-use graphical interface for scRNA-Seq data analysis. The package is freely available for research use at http://garmiregroup.org/granatum/app

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bioRxiv2016

Cox-nnet: an artificial neural network Cox regression for prognosis prediction

Artificial neural networks (ANN) are computing architectures with massively parallel interconnections of simple neurons and has been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosis from high throughput transcriptomics data. In over 10 TCGA RNA-Seq data sets, Cox-nnet achieves a statistically significant increase in predictive accuracy, compared to the other three methods including Cox-proportional hazards (Cox-PH), Random Forests Survival and CoxBoost. Cox-nnet also reveals richer biological information, from both pathway and gene levels. The outputs from the hidden layer node can provide a new approach for survival-sensitive dimension reduction. In summary, we have developed a new method for more accurate and efficient prognosis prediction on high throughput data, with functional biological insights. The source code is freely available at github.com/lanagarmire/cox-nnet.

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