scholarly journals Robust Identification of Temporal Biomarkers in Longitudinal Omics Studies

2021 ◽  
Author(s):  
Ahmed A. Metwally ◽  
Tom Zhang ◽  
Si Wu ◽  
Ryan Kellogg ◽  
Wenyu Zhou ◽  
...  

Longitudinal studies increasingly collect rich 'omics' data sampled frequently over time and across large cohorts to capture dynamic health fluctuations and disease transitions. However, the generation of longitudinal omics data has preceded the development of analysis tools that can efficiently extract insights from such data. In particular, there is a need for statistical frameworks that can identify not only which omics features are differentially regulated between groups but also over what time intervals. Additionally, longitudinal omics data may have inconsistencies, including nonuniform sampling intervals, missing data points, subject dropout, and differing numbers of samples per subject. In this work, we developed a statistical method that provides robust identification of time intervals of temporal omics biomarkers. The proposed method is based on a semi-parametric approach, in which we use smoothing splines to model longitudinal data and infer significant time intervals of omics features based on an empirical distribution constructed through a permutation procedure. We benchmarked the proposed method on five simulated datasets with diverse temporal patterns, and the method showed specificity greater than 0.99 and sensitivity greater than 0.72. Applying the proposed method to the Integrative Personal Omics Profiling (iPOP) cohort revealed temporal patterns of amino acids, lipids, and hormone metabolites that are differentially regulated in male versus female subjects following a respiratory infection. In addition, we applied the longitudinal multi-omics dataset of pregnant women with and without preeclampsia, and the method identified potential lipid markers that are temporally significantly different between the two groups. We provide an open-source R package, OmicsLonDA (Omics Longitudinal Differential Analysis): https://bioconductor.org/packages/OmicsLonDA to enable widespread use.

2021 ◽  
Vol 22 (3) ◽  
pp. 1399
Author(s):  
Salim Ghannoum ◽  
Waldir Leoncio Netto ◽  
Damiano Fantini ◽  
Benjamin Ragan-Kelley ◽  
Amirabbas Parizadeh ◽  
...  

The growing attention toward the benefits of single-cell RNA sequencing (scRNA-seq) is leading to a myriad of computational packages for the analysis of different aspects of scRNA-seq data. For researchers without advanced programing skills, it is very challenging to combine several packages in order to perform the desired analysis in a simple and reproducible way. Here we present DIscBIO, an open-source, multi-algorithmic pipeline for easy, efficient and reproducible analysis of cellular sub-populations at the transcriptomic level. The pipeline integrates multiple scRNA-seq packages and allows biomarker discovery with decision trees and gene enrichment analysis in a network context using single-cell sequencing read counts through clustering and differential analysis. DIscBIO is freely available as an R package. It can be run either in command-line mode or through a user-friendly computational pipeline using Jupyter notebooks. We showcase all pipeline features using two scRNA-seq datasets. The first dataset consists of circulating tumor cells from patients with breast cancer. The second one is a cell cycle regulation dataset in myxoid liposarcoma. All analyses are available as notebooks that integrate in a sequential narrative R code with explanatory text and output data and images. R users can use the notebooks to understand the different steps of the pipeline and will guide them to explore their scRNA-seq data. We also provide a cloud version using Binder that allows the execution of the pipeline without the need of downloading R, Jupyter or any of the packages used by the pipeline. The cloud version can serve as a tutorial for training purposes, especially for those that are not R users or have limited programing skills. However, in order to do meaningful scRNA-seq analyses, all users will need to understand the implemented methods and their possible options and limitations.


2019 ◽  
Author(s):  
Wikum Dinalankara ◽  
Qian Ke ◽  
Donald Geman ◽  
Luigi Marchionni

AbstractGiven the ever-increasing amount of high-dimensional and complex omics data becoming available, it is increasingly important to discover simple but effective methods of analysis. Divergence analysis transforms each entry of a high-dimensional omics profile into a digitized (binary or ternary) code based on the deviation of the entry from a given baseline population. This is a novel framework that is significantly different from existing omics data analysis methods: it allows digitization of continuous omics data at the univariate or multivariate level, facilitates sample level analysis, and is applicable on many different omics platforms. The divergence package, available on the R platform through the Bioconductor repository collection, provides easy-to-use functions for carrying out this transformation. Here we demonstrate how to use the package with sample high throughput sequencing data from the Cancer Genome Atlas.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249002
Author(s):  
Wikum Dinalankara ◽  
Qian Ke ◽  
Donald Geman ◽  
Luigi Marchionni

Given the ever-increasing amount of high-dimensional and complex omics data becoming available, it is increasingly important to discover simple but effective methods of analysis. Divergence analysis transforms each entry of a high-dimensional omics profile into a digitized (binary or ternary) code based on the deviation of the entry from a given baseline population. This is a novel framework that is significantly different from existing omics data analysis methods: it allows digitization of continuous omics data at the univariate or multivariate level, facilitates sample level analysis, and is applicable on many different omics platforms. The divergence package, available on the R platform through the Bioconductor repository collection, provides easy-to-use functions for carrying out this transformation. Here we demonstrate how to use the package with data from the Cancer Genome Atlas.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Benjamin Ulfenborg

Abstract Background Studies on multiple modalities of omics data such as transcriptomics, genomics and proteomics are growing in popularity, since they allow us to investigate complex mechanisms across molecular layers. It is widely recognized that integrative omics analysis holds the promise to unlock novel and actionable biological insights into health and disease. Integration of multi-omics data remains challenging, however, and requires combination of several software tools and extensive technical expertise to account for the properties of heterogeneous data. Results This paper presents the miodin R package, which provides a streamlined workflow-based syntax for multi-omics data analysis. The package allows users to perform analysis of omics data either across experiments on the same samples (vertical integration), or across studies on the same variables (horizontal integration). Workflows have been designed to promote transparent data analysis and reduce the technical expertise required to perform low-level data import and processing. Conclusions The miodin package is implemented in R and is freely available for use and extension under the GPL-3 license. Package source, reference documentation and user manual are available at https://gitlab.com/algoromics/miodin.


2020 ◽  
Vol 14 ◽  
pp. 117955492096626
Author(s):  
Yun Liu ◽  
Fu Liu ◽  
Xintong Hu ◽  
Jiaxue He ◽  
Yanfang Jiang

Motivation: Although several prognostic signatures for lung adenocarcinoma (LUAD) have been developed, they are mainly based on a single-omics data set. This article aims to develop a novel set of prognostic signatures by combining genetic mutation and expression profiles of LUAD patients. Methods: The genetic mutation and expression profiles, together with the clinical profiles of a cohort of LUAD patients from The Cancer Genome Atlas (TCGA), were downloaded. Patients were separated into 2 groups, namely, the high-risk and low-risk groups, according to their overall survivals. Then, differential analysis was performed to determine differentially expressed genes (DEGs) and mutated genes (DMGs) in the expression and mutation profiles, respectively, between the 2 groups. Finally, a prognostic model based on the support vector machine (SVM) algorithm was developed by combining the expression values of the DEGs and the mutation times of the DMGs. Results: A total of 13 DEGs and 7 DMGs were recognized between the 2 groups. Their prognostic values were validated using independent cohorts. Compared with several existing signatures, the proposed prognostic signatures exhibited better prediction performance in the testing set. In addition, it is found that 1 of the 7 DMGs, GRIN2B, is mutated much more frequently in the high-risk group, showing a potential value as a therapy target. Conclusions: Combining multi-omics data sets is an applicable manner to identify novel prognostic signatures and to improve the prognostic prediction for LUAD, which will be heuristic to other types of cancers.


Author(s):  
Shixiang Wang ◽  
Yi Xiong ◽  
Kai Gu ◽  
Longfei Zhao ◽  
Yin Li ◽  
...  

Motivation: UCSC Xena platform provides huge amounts of processed cancer omics data from big public projects like TCGA or individual reserach groups for enabling unprecedented research opportunities. In 2019, we developed UCSCXenaTools, an R package for retrieval of UCSC Xena data. However, an easier dataset exploration and analysis tool is still lack, especially for researchers without programming experience. Results: We develop UCSCXenaShiny, an R Shiny package to quickly explore, download all datasets from UCSC Xena data hubs. In addiction, a module based analysis framework is constructed to analyze and visualize data. Availability: https://github.com/openbiox/UCSCXenaShiny or https://cran.r-project.org/package=UCSCXenaShiny.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 538
Author(s):  
Tyrone Chen ◽  
Al J Abadi ◽  
Kim-Anh Lê Cao ◽  
Sonika Tyagi

Data from multiple omics layers of a biological system is growing in quantity, heterogeneity and dimensionality. Simultaneous multi-omics data integration is a growing field of research as it has strong potential to unlock information on previously hidden biological relationships leading to early diagnosis, prognosis and expedited treatments. Many tools for multi-omics data integration are being developed. However, these tools are often restricted to highly specific experimental designs, and types of omics data. While some general methods do exist, they require specific data formats and experimental conditions. A major limitation in the field is a lack of a single or multi-omics pipeline which can accept data in an unrefined, information-rich form pre-integration and subsequently generate output for further investigation. There is an increasing demand for a generic multi-omics pipeline to facilitate general-purpose data exploration and analysis of heterogeneous data. Therefore, we present our R multiomics pipeline as an easy to use and flexible pipeline that takes unrefined multi-omics data as input, sample information and user-specified parameters to generate a list of output plots and data tables for quality control and downstream analysis. We have demonstrated application of the pipeline on two separate COVID-19 case studies. We enabled limited checkpointing where intermediate output is staged to allow continuation after errors or interruptions in the pipeline and generate a script for reproducing the analysis to improve reproducibility. A seamless integration with the mixOmics R package is achieved, as the R data object can be loaded and manipulated with mixOmics functions. Our pipeline can be installed as an R package or from the git repository, and is accompanied by detailed documentation with walkthroughs on two case studies. The pipeline is also available as Docker and Singularity containers.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 7
Author(s):  
Sebastien Theil ◽  
Etienne Rifa

Bioinformatic tools for marker gene sequencing data analysis are continuously and rapidly evolving, thus integrating most recent techniques and tools is challenging. We present an R package for data analysis of 16S and ITS amplicons based sequencing. This workflow is based on several R functions and performs automatic treatments from fastq sequence files to diversity and differential analysis with statistical validation. The main purpose of this package is to automate bioinformatic analysis, ensure reproducibility between projects, and to be flexible enough to quickly integrate new bioinformatic tools or statistical methods. rANOMALY is an easy to install and customizable R package, that uses amplicon sequence variants (ASV) level for microbial community characterization. It integrates all assets of the latest bioinformatics methods, such as better sequence tracking, decontamination from control samples, use of multiple reference databases for taxonomic annotation, all main ecological analysis for which we propose advanced statistical tests, and a cross-validated differential analysis by four different methods. Our package produces ready to publish figures, and all of its outputs are made to be integrated in Rmarkdown code to produce automated reports.


2019 ◽  
Vol 36 (3) ◽  
pp. 842-850 ◽  
Author(s):  
Cheng Peng ◽  
Jun Wang ◽  
Isaac Asante ◽  
Stan Louie ◽  
Ran Jin ◽  
...  

Abstract Motivation Epidemiologic, clinical and translational studies are increasingly generating multiplatform omics data. Methods that can integrate across multiple high-dimensional data types while accounting for differential patterns are critical for uncovering novel associations and underlying relevant subgroups. Results We propose an integrative model to estimate latent unknown clusters (LUCID) aiming to both distinguish unique genomic, exposure and informative biomarkers/omic effects while jointly estimating subgroups relevant to the outcome of interest. Simulation studies indicate that we can obtain consistent estimates reflective of the true simulated values, accurately estimate subgroups and recapitulate subgroup-specific effects. We also demonstrate the use of the integrated model for future prediction of risk subgroups and phenotypes. We apply this approach to two real data applications to highlight the integration of genomic, exposure and metabolomic data. Availability and Implementation The LUCID method is implemented through the LUCIDus R package available on CRAN (https://CRAN.R-project.org/package=LUCIDus). Supplementary information Supplementary materials are available at Bioinformatics online.


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