Spathial: an R package for the evolutionary analysis of biological data

Abstract Summary A primary problem in high-throughput genomics experiments is finding the most important genes involved in biological processes (e.g. tumor progression). In this applications note, we introduce spathial, an R package for navigating high-dimensional data spaces. spathial implements the Principal Path algorithm, which is a topological method for locally navigating on the data manifold. The package, together with the core algorithm, provides several high-level functions for interpreting the results. One of the analyses we propose is the extraction of the genes that are mainly involved in the progress from one state to another. We show a possible application in the context of tumor progression using RNA-Seq and single-cell datasets, and we compare our results with two commonly used algorithms, edgeR and monocle3, respectively. Availability and implementation The R package spathial is available on the Comprehensive R Archive Network (https://cran.r-project.org/web/packages/spathial/index.html) and on GitHub (https://github.com/erikagardini/spathial). It is distributed under the GNU General Public License (version 3). Supplementary information Supplementary data are available at Bioinformatics online.

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Automatic identification of relevant genes from low-dimensional embeddings of single-cell RNA-seq data

Bioinformatics ◽

10.1093/bioinformatics/btaa198 ◽

2020 ◽

Vol 36 (15) ◽

pp. 4291-4295

Author(s):

Philipp Angerer ◽

David S Fischer ◽

Fabian J Theis ◽

Antonio Scialdone ◽

Carsten Marr

Keyword(s):

Single Cell ◽

Principal Component ◽

R Package ◽

Ease Of Use ◽

Supplementary Information ◽

Automatic Identification ◽

Biological Processes ◽

Rna Seq ◽

Sequencing Data ◽

Low Dimensional

Abstract Motivation Dimensionality reduction is a key step in the analysis of single-cell RNA-sequencing data. It produces a low-dimensional embedding for visualization and as a calculation base for downstream analysis. Nonlinear techniques are most suitable to handle the intrinsic complexity of large, heterogeneous single-cell data. However, with no linear relation between gene and embedding coordinate, there is no way to extract the identity of genes driving any cell’s position in the low-dimensional embedding, making it difficult to characterize the underlying biological processes. Results In this article, we introduce the concepts of local and global gene relevance to compute an equivalent of principal component analysis loadings for non-linear low-dimensional embeddings. Global gene relevance identifies drivers of the overall embedding, while local gene relevance identifies those of a defined sub-region. We apply our method to single-cell RNA-seq datasets from different experimental protocols and to different low-dimensional embedding techniques. This shows our method’s versatility to identify key genes for a variety of biological processes. Availability and implementation To ensure reproducibility and ease of use, our method is released as part of destiny 3.0, a popular R package for building diffusion maps from single-cell transcriptomic data. It is readily available through Bioconductor. Supplementary information Supplementary data are available at Bioinformatics online.

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ExperimentSubset: an R package to manage subsets of Bioconductor Experiment objects

Bioinformatics ◽

10.1093/bioinformatics/btab179 ◽

2021 ◽

Author(s):

Irzam Sarfraz ◽

Muhammad Asif ◽

Joshua D Campbell

Keyword(s):

Single Cell ◽

R Package ◽

Poor Quality ◽

Data Matrix ◽

Supplementary Information ◽

Data Provenance ◽

Rna Seq ◽

Efficient Management ◽

The Matrix ◽

The Relationship

Abstract Motivation R Experiment objects such as the SummarizedExperiment or SingleCellExperiment are data containers for storing one or more matrix-like assays along with associated row and column data. These objects have been used to facilitate the storage and analysis of high-throughput genomic data generated from technologies such as single-cell RNA sequencing. One common computational task in many genomics analysis workflows is to perform subsetting of the data matrix before applying down-stream analytical methods. For example, one may need to subset the columns of the assay matrix to exclude poor-quality samples or subset the rows of the matrix to select the most variable features. Traditionally, a second object is created that contains the desired subset of assay from the original object. However, this approach is inefficient as it requires the creation of an additional object containing a copy of the original assay and leads to challenges with data provenance. Results To overcome these challenges, we developed an R package called ExperimentSubset, which is a data container that implements classes for efficient storage and streamlined retrieval of assays that have been subsetted by rows and/or columns. These classes are able to inherently provide data provenance by maintaining the relationship between the subsetted and parent assays. We demonstrate the utility of this package on a single-cell RNA-seq dataset by storing and retrieving subsets at different stages of the analysis while maintaining a lower memory footprint. Overall, the ExperimentSubset is a flexible container for the efficient management of subsets. Availability and implementation ExperimentSubset package is available at Bioconductor: https://bioconductor.org/packages/ExperimentSubset/ and Github: https://github.com/campbio/ExperimentSubset. Supplementary information Supplementary data are available at Bioinformatics online.

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movAPA: modeling and visualization of dynamics of alternative polyadenylation across biological samples

Bioinformatics ◽

10.1093/bioinformatics/btaa997 ◽

2020 ◽

Author(s):

Wenbin Ye ◽

Tao Liu ◽

Hongjuan Fu ◽

Congting Ye ◽

Guoli Ji ◽

...

Keyword(s):

Biological Samples ◽

Tissue Specificity ◽

Single Cells ◽

Alternative Polyadenylation ◽

R Package ◽

Supplementary Information ◽

Rna Seq ◽

Mouse Sperm ◽

High Scalability ◽

A Site

Abstract Motivation Alternative polyadenylation (APA) has been widely recognized as a widespread mechanism modulated dynamically. Studies based on 3′ end sequencing and/or RNA-seq have profiled poly(A) sites in various species with diverse pipelines, yet no unified and easy-to-use toolkit is available for comprehensive APA analyses. Results We developed an R package called movAPA for modeling and visualization of dynamics of alternative polyadenylation across biological samples. movAPA incorporates rich functions for preprocessing, annotation and statistical analyses of poly(A) sites, identification of poly(A) signals, profiling of APA dynamics and visualization. Particularly, seven metrics are provided for measuring the tissue-specificity or usages of APA sites across samples. Three methods are used for identifying 3′ UTR shortening/lengthening events between conditions. APA site switching involving non-3′ UTR polyadenylation can also be explored. Using poly(A) site data from rice and mouse sperm cells, we demonstrated the high scalability and flexibility of movAPA in profiling APA dynamics across tissues and single cells. Availability and implementation https://github.com/BMILAB/movAPA. Supplementary information Supplementary data are available at Bioinformatics online.

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DEsingle for detecting three types of differential expression in single-cell RNA-seq data

10.1101/173997 ◽

2017 ◽

Cited By ~ 1

Author(s):

Zhun Miao ◽

Ke Deng ◽

Xiaowo Wang ◽

Xuegong Zhang

Keyword(s):

Single Cell ◽

Differential Expression ◽

Negative Binomial ◽

Single Cells ◽

R Package ◽

Supplementary Information ◽

Binomial Model ◽

Supplementary Data ◽

Rna Seq ◽

Real Zeros

AbstractSummaryThe excessive amount of zeros in single-cell RNA-seq data include “real” zeros due to the on-off nature of gene transcription in single cells and “dropout” zeros due to technical reasons. Existing differential expression (DE) analysis methods cannot distinguish these two types of zeros. We developed an R package DEsingle which employed Zero-Inflated Negative Binomial model to estimate the proportion of real and dropout zeros and to define and detect 3 types of DE genes in single-cell RNA-seq data with higher accuracy.Availability and ImplementationThe R package DEsingle is freely available at https://github.com/miaozhun/DEsingle and is under Bioconductor’s consideration [email protected] informationSupplementary data are available at bioRxiv online.

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DiscoRhythm: an easy-to-use web application and R package for discovering rhythmicity

Bioinformatics ◽

10.1093/bioinformatics/btz834 ◽

2019 ◽

Cited By ~ 2

Author(s):

Matthew Carlucci ◽

Algimantas Kriščiūnas ◽

Haohan Li ◽

Povilas Gibas ◽

Karolis Koncevičius ◽

...

Keyword(s):

Web Application ◽

Statistical Significance ◽

R Package ◽

Biological Data ◽

Supplementary Information ◽

Statistical Knowledge ◽

Health And Disease ◽

Phase Amplitude ◽

Almost All ◽

User Friendly

Abstract Motivation Biological rhythmicity is fundamental to almost all organisms on Earth and plays a key role in health and disease. Identification of oscillating signals could lead to novel biological insights, yet its investigation is impeded by the extensive computational and statistical knowledge required to perform such analysis. Results To address this issue, we present DiscoRhythm (Discovering Rhythmicity), a user-friendly application for characterizing rhythmicity in temporal biological data. DiscoRhythm is available as a web application or an R/Bioconductor package for estimating phase, amplitude, and statistical significance using four popular approaches to rhythm detection (Cosinor, JTK Cycle, ARSER, and Lomb-Scargle). We optimized these algorithms for speed, improving their execution times up to 30-fold to enable rapid analysis of -omic-scale datasets in real-time. Informative visualizations, interactive modules for quality control, dimensionality reduction, periodicity profiling, and incorporation of experimental replicates make DiscoRhythm a thorough toolkit for analyzing rhythmicity. Availability and Implementation The DiscoRhythm R package is available on Bioconductor (https://bioconductor.org/packages/DiscoRhythm), with source code available on GitHub (https://github.com/matthewcarlucci/DiscoRhythm) under a GPL-3 license. The web application is securely deployed over HTTPS (https://disco.camh.ca) and is freely available for use worldwide. Local instances of the DiscoRhythm web application can be created using the R package or by deploying the publicly available Docker container (https://hub.docker.com/r/mcarlucci/discorhythm). Supplementary information Supplementary data are available at Bioinformatics online.

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DECENT: differential expression with capture efficiency adjustmeNT for single-cell RNA-seq data

Bioinformatics ◽

10.1093/bioinformatics/btz453 ◽

2019 ◽

Vol 35 (24) ◽

pp. 5155-5162 ◽

Cited By ~ 10

Author(s):

Chengzhong Ye ◽

Terence P Speed ◽

Agus Salim

Keyword(s):

Single Cell ◽

Differential Expression ◽

Type I Error ◽

R Package ◽

Supplementary Information ◽

Type I ◽

Common Phenomenon ◽

Rna Seq ◽

Capture Process ◽

Technological Platforms

Abstract Motivation Dropout is a common phenomenon in single-cell RNA-seq (scRNA-seq) data, and when left unaddressed it affects the validity of the statistical analyses. Despite this, few current methods for differential expression (DE) analysis of scRNA-seq data explicitly model the process that gives rise to the dropout events. We develop DECENT, a method for DE analysis of scRNA-seq data that explicitly and accurately models the molecule capture process in scRNA-seq experiments. Results We show that DECENT demonstrates improved DE performance over existing DE methods that do not explicitly model dropout. This improvement is consistently observed across several public scRNA-seq datasets generated using different technological platforms. The gain in improvement is especially large when the capture process is overdispersed. DECENT maintains type I error well while achieving better sensitivity. Its performance without spike-ins is almost as good as when spike-ins are used to calibrate the capture model. Availability and implementation The method is implemented as a publicly available R package available from https://github.com/cz-ye/DECENT. Supplementary information Supplementary data are available at Bioinformatics online.

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Inferring cellular heterogeneity of associations from single cell genomics

Bioinformatics ◽

10.1093/bioinformatics/btaa151 ◽

2020 ◽

Vol 36 (11) ◽

pp. 3466-3473

Author(s):

Maya Levy ◽

Amit Frishberg ◽

Irit Gat-Viks

Keyword(s):

Simulated Data ◽

R Package ◽

Biological Data ◽

Cellular Heterogeneity ◽

Supplementary Information ◽

Dynamic Changes ◽

Entire Cell ◽

Complete Set ◽

Cellular Phenotypes ◽

Cell Variation

Abstract Motivation Cell-to-cell variation has uncovered associations between cellular phenotypes. However, it remains challenging to address the cellular diversity of such associations. Results Here, we do not rely on the conventional assumption that the same association holds throughout the entire cell population. Instead, we assume that associations may exist in a certain subset of the cells. We developed CEllular Niche Association (CENA) to reliably predict pairwise associations together with the cell subsets in which the associations are detected. CENA does not rely on predefined subsets but only requires that the cells of each predicted subset would share a certain characteristic state. CENA may therefore reveal dynamic modulation of dependencies along cellular trajectories of temporally evolving states. Using simulated data, we show the advantage of CENA over existing methods and its scalability to a large number of cells. Application of CENA to real biological data demonstrates dynamic changes in associations that would be otherwise masked. Availability and implementation CENA is available as an R package at Github: https://github.com/mayalevy/CENA and is accompanied by a complete set of documentations and instructions. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

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Two-stage Linked Component Analysis for Joint Decomposition of Multiple Biologically Related Data Sets

10.1101/2021.03.22.435728 ◽

2021 ◽

Author(s):

By Huan Chen ◽

Brian Caffo ◽

Genevieve Stein-O’Brien ◽

Jinrui Liu ◽

Ben Langmead ◽

...

Keyword(s):

R Package ◽

Component Analysis ◽

Biological Data ◽

Joint Analysis ◽

Data Sets ◽

Biological Processes ◽

Two Stage ◽

Data Set ◽

Multiple Data ◽

Multiple Data Sets

SummaryIntegrative analysis of multiple data sets has the potential of fully leveraging the vast amount of high throughput biological data being generated. In particular such analysis will be powerful in making inference from publicly available collections of genetic, transcriptomic and epigenetic data sets which are designed to study shared biological processes, but which vary in their target measurements, biological variation, unwanted noise, and batch variation. Thus, methods that enable the joint analysis of multiple data sets are needed to gain insights into shared biological processes that would otherwise be hidden by unwanted intra-data set variation. Here, we propose a method called two-stage linked component analysis (2s-LCA) to jointly decompose multiple biologically related experimental data sets with biological and technological relationships that can be structured into the decomposition. The consistency of the proposed method is established and its empirical performance is evaluated via simulation studies. We apply 2s-LCA to jointly analyze four data sets focused on human brain development and identify meaningful patterns of gene expression in human neurogenesis that have shared structure across these data sets. The code to conduct 2s-LCA has been complied into an R package “PJD”, which is available at https://github.com/CHuanSite/PJD.

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Identification of disease-associated loci using machine learning for genotype and network data integration

Bioinformatics ◽

10.1093/bioinformatics/btz310 ◽

2019 ◽

Vol 35 (24) ◽

pp. 5182-5190 ◽

Cited By ~ 4

Author(s):

Luis G Leal ◽

Alessia David ◽

Marjo-Riita Jarvelin ◽

Sylvain Sebert ◽

Minna Männikkö ◽

...

Keyword(s):

Machine Learning ◽

Gene Networks ◽

Association Studies ◽

R Package ◽

Biological Data ◽

Machine Learning Algorithms ◽

Supplementary Information ◽

Genome Wide Association Studies ◽

Omics Data ◽

Missing Heritability

Abstract Motivation Integration of different omics data could markedly help to identify biological signatures, understand the missing heritability of complex diseases and ultimately achieve personalized medicine. Standard regression models used in Genome-Wide Association Studies (GWAS) identify loci with a strong effect size, whereas GWAS meta-analyses are often needed to capture weak loci contributing to the missing heritability. Development of novel machine learning algorithms for merging genotype data with other omics data is highly needed as it could enhance the prioritization of weak loci. Results We developed cNMTF (corrected non-negative matrix tri-factorization), an integrative algorithm based on clustering techniques of biological data. This method assesses the inter-relatedness between genotypes, phenotypes, the damaging effect of the variants and gene networks in order to identify loci-trait associations. cNMTF was used to prioritize genes associated with lipid traits in two population cohorts. We replicated 129 genes reported in GWAS world-wide and provided evidence that supports 85% of our findings (226 out of 265 genes), including recent associations in literature (NLGN1), regulators of lipid metabolism (DAB1) and pleiotropic genes for lipid traits (CARM1). Moreover, cNMTF performed efficiently against strong population structures by accounting for the individuals’ ancestry. As the method is flexible in the incorporation of diverse omics data sources, it can be easily adapted to the user’s research needs. Availability and implementation An R package (cnmtf) is available at https://lgl15.github.io/cnmtf_web/index.html. Supplementary information Supplementary data are available at Bioinformatics online.

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scRNABatchQC: multi-samples quality control for single cell RNA-seq data

Bioinformatics ◽

10.1093/bioinformatics/btz601 ◽

2019 ◽

Vol 35 (24) ◽

pp. 5306-5308

Author(s):

Qi Liu ◽

Quanhu Sheng ◽

Jie Ping ◽

Marisol Adelina Ramirez ◽

Ken S Lau ◽

...

Keyword(s):

Single Cell ◽

R Package ◽

Supplementary Information ◽

Rna Seq ◽

Technical Artifact ◽

Multiple Sample ◽

Systematic Biases ◽

Cell Transcriptome ◽

Single Cell Transcriptome ◽

Spurious Results

Abstract Summary Single cell RNA sequencing is a revolutionary technique to characterize inter-cellular transcriptomics heterogeneity. However, the data are noise-prone because gene expression is often driven by both technical artifacts and genuine biological variations. Proper disentanglement of these two effects is critical to prevent spurious results. While several tools exist to detect and remove low-quality cells in one single cell RNA-seq dataset, there is lack of approach to examining consistency between sample sets and detecting systematic biases, batch effects and outliers. We present scRNABatchQC, an R package to compare multiple sample sets simultaneously over numerous technical and biological features, which gives valuable hints to distinguish technical artifact from biological variations. scRNABatchQC helps identify and systematically characterize sources of variability in single cell transcriptome data. The examination of consistency across datasets allows visual detection of biases and outliers. Availability and implementation scRNABatchQC is freely available at https://github.com/liuqivandy/scRNABatchQC as an R package. Supplementary information Supplementary data are available at Bioinformatics online.

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