scholarly journals Block HSIC Lasso: model-free biomarker detection for ultra-high dimensional data

2019 ◽  
Author(s):  
Héctor Climente-González ◽  
Chloé-Agathe Azencott ◽  
Samuel Kaski ◽  
Makoto Yamada
Keyword(s):  
Single Cell ◽  
Synthetic Data ◽  
Real Data ◽  
Supplementary Information ◽  
Rna Seq ◽  
Link Type ◽  
Model Free ◽  
Computational Overhead ◽  
Expression Microarrays ◽  
And Function

AbstractMotivationFinding nonlinear relationships between biomolecules and a biological outcome is computationally expensive and statistically challenging. Existing methods have crucial drawbacks, among others lack of parsimony, non-convexity, and computational overhead. Here we present the block HSIC Lasso, a nonlinear feature selector that does not present the previous drawbacks.ResultsWe compare the block HSIC Lasso to other state-of-the-art feature selection techniques in synthetic data and real data, including experiments over three common types of genomic data: gene-expression microarrays, single-cell RNA-seq, and GWAS. In all the cases, we observe that features selected by block HSIC Lasso retain more information about the underlying biology than features of other techniques. As a proof of concept, we applied the block HSIC Lasso to a single-cell RNA-seq experiment on mouse hippocampus. We discovered that many genes linked in the past to brain development and function are involved in the biological differences between the types of neurons.AvailabilityBlock HSIC Lasso is implemented in the Python 2/3 package pyHSICLasso, available in Github (https://github.com/riken-aip/pyHSICLasso) and PyPi (https://pypi.org/project/pyHSICLasso)[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Block HSIC Lasso: model-free biomarker detection for ultra-high dimensional data

2019 ◽  
Vol 35 (14) ◽  
pp. i427-i435 ◽  
Author(s):  
Héctor Climente-González ◽  
Chloé-Agathe Azencott ◽  
Samuel Kaski ◽  
Makoto Yamada
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Association Studies ◽  
Real Data ◽  
Supplementary Information ◽  
Genome Wide Association Studies ◽  
Model Free ◽  
Computational Overhead ◽  
Single Cell Rna Sequencing ◽  
Non Linear

AbstractMotivationFinding non-linear relationships between biomolecules and a biological outcome is computationally expensive and statistically challenging. Existing methods have important drawbacks, including among others lack of parsimony, non-convexity and computational overhead. Here we propose block HSIC Lasso, a non-linear feature selector that does not present the previous drawbacks.ResultsWe compare block HSIC Lasso to other state-of-the-art feature selection techniques in both synthetic and real data, including experiments over three common types of genomic data: gene-expression microarrays, single-cell RNA sequencing and genome-wide association studies. In all cases, we observe that features selected by block HSIC Lasso retain more information about the underlying biology than those selected by other techniques. As a proof of concept, we applied block HSIC Lasso to a single-cell RNA sequencing experiment on mouse hippocampus. We discovered that many genes linked in the past to brain development and function are involved in the biological differences between the types of neurons.Availability and implementationBlock HSIC Lasso is implemented in the Python 2/3 package pyHSICLasso, available on PyPI. Source code is available on GitHub (https://github.com/riken-aip/pyHSICLasso).Supplementary informationSupplementary data are available at Bioinformatics online.

scholarly journals scBatch: batch-effect correction of RNA-seq data through sample distance matrix adjustment

2020 ◽  
Vol 36 (10) ◽  
pp. 3115-3123 ◽  
Author(s):  
Teng Fei ◽  
Tianwei Yu
Keyword(s):  
Single Cell ◽  
Differential Expression Analysis ◽  
Distance Matrix ◽  
Real Data ◽  
R Package ◽  
Batch Effect ◽  
Supplementary Information ◽  
Rna Seq ◽  
Sequencing Data ◽  
Gene Differential Expression

Abstract Motivation Batch effect is a frequent challenge in deep sequencing data analysis that can lead to misleading conclusions. Existing methods do not correct batch effects satisfactorily, especially with single-cell RNA sequencing (RNA-seq) data. Results We present scBatch, a numerical algorithm for batch-effect correction on bulk and single-cell RNA-seq data with emphasis on improving both clustering and gene differential expression analysis. scBatch is not restricted by assumptions on the mechanism of batch-effect generation. As shown in simulations and real data analyses, scBatch outperforms benchmark batch-effect correction methods. Availability and implementation The R package is available at github.com/tengfei-emory/scBatch. The code to generate results and figures in this article is available at github.com/tengfei-emory/scBatch-paper-scripts. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals SPARSim single cell: a count data simulator for scRNA-seq data

2019 ◽  
Author(s):  
Giacomo Baruzzo ◽  
Ilaria Patuzzi ◽  
Barbara Di Camillo
Keyword(s):  
Single Cell ◽  
Count Data ◽  
Simulated Data ◽  
Real Data ◽  
R Package ◽  
Supplementary Information ◽  
Rna Seq ◽  
Distribution Of Zeros ◽  
New Methods ◽  
Research Fields

Abstract Motivation Single cell RNA-seq (scRNA-seq) count data show many differences compared with bulk RNA-seq count data, making the application of many RNA-seq pre-processing/analysis methods not straightforward or even inappropriate. For this reason, the development of new methods for handling scRNA-seq count data is currently one of the most active research fields in bioinformatics. To help the development of such new methods, the availability of simulated data could play a pivotal role. However, only few scRNA-seq count data simulators are available, often showing poor or not demonstrated similarity with real data. Results In this article we present SPARSim, a scRNA-seq count data simulator based on a Gamma-Multivariate Hypergeometric model. We demonstrate that SPARSim allows to generate count data that resemble real data in terms of count intensity, variability and sparsity, performing comparably or better than one of the most used scRNA-seq simulator, Splat. In particular, SPARSim simulated count matrices well resemble the distribution of zeros across different expression intensities observed in real count data. Availability and implementation SPARSim R package is freely available at http://sysbiobig.dei.unipd.it/? q=SPARSim and at https://gitlab.com/sysbiobig/sparsim. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Comprehensive evaluation of computational cell-type quantification methods for immuno-oncology

2018 ◽  
Author(s):  
Gregor Sturm ◽  
Francesca Finotello ◽  
Florent Petitprez ◽  
Jitao David Zhang ◽  
Jan Baumbach ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Computational Methods ◽  
Immune Cell ◽  
Comprehensive Evaluation ◽  
Supplementary Information ◽  
Rna Seq ◽  
Cell Type ◽  
Link Type ◽  
Real World Datasets

AbstractMotivationThe composition and density of immune cells in the tumor microenvironment profoundly influence tumor progression and success of anti-cancer therapies. Flow cytometry, immunohistochemistry staining, or single-cell sequencing is often unavailable such that we rely on computational methods to estimate the immune-cell composition from bulk RNA-sequencing (RNA-seq) data. Various methods have been proposed recently, yet their capabilities and limitations have not been evaluated systematically. A general guideline leading the research community through cell type deconvolution is missing.ResultsWe developed a systematic approach for benchmarking such computational methods and assessed the accuracy of tools at estimating nine different immune- and stromal cells from bulk RNA-seq samples. We used a single-cell RNA-seq dataset of ∼11,000 cells from the tumor microenvironment to simulate bulk samples of known cell type proportions, and validated the results using independent, publicly available gold-standard estimates. This allowed us to analyze and condense the results of more than a hundred thousand predictions to provide an exhaustive evaluation across seven computational methods over nine cell types and ∼1,800 samples from five simulated and real-world datasets. We demonstrate that computational deconvolution performs at high accuracy for well-defined cell-type signatures and propose how fuzzy cell-type signatures can be improved. We suggest that future efforts should be dedicated to refining cell population definitions and finding reliable signatures.AvailabilityA snakemake pipeline to reproduce the benchmark is available at https://github.com/grst/immune_deconvolution_benchmark. An R package allows the community to perform integrated deconvolution using different methods (https://grst.github.io/immunedeconv)[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Gene regulation inference from single-cell RNA-seq data with linear differential equations and velocity inference

2020 ◽  
Vol 36 (18) ◽  
pp. 4774-4780 ◽  
Author(s):  
Pierre-Cyril Aubin-Frankowski ◽  
Jean-Philippe Vert
Keyword(s):  
Single Cell ◽  
De Novo ◽  
Real Data ◽  
Supplementary Information ◽  
Biological Processes ◽  
Rna Seq ◽  
Cell Cycles ◽  
Gene Regulatory ◽  
Linear Differential ◽  
Cell Trajectories

Abstract Motivation Single-cell RNA sequencing (scRNA-seq) offers new possibilities to infer gene regulatory network (GRNs) for biological processes involving a notion of time, such as cell differentiation or cell cycles. It also raises many challenges due to the destructive measurements inherent to the technology. Results In this work, we propose a new method named GRISLI for de novo GRN inference from scRNA-seq data. GRISLI infers a velocity vector field in the space of scRNA-seq data from profiles of individual cells, and models the dynamics of cell trajectories with a linear ordinary differential equation to reconstruct the underlying GRN with a sparse regression procedure. We show on real data that GRISLI outperforms a recently proposed state-of-the-art method for GRN reconstruction from scRNA-seq data. Availability and implementation The MATLAB code of GRISLI is available at: https://github.com/PCAubin/GRISLI. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals The winning methods for predicting cellular position in the DREAM single cell transcriptomics challenge

2020 ◽  
Author(s):  
Vu VH Pham ◽  
Xiaomei Li ◽  
Buu Truong ◽  
Thin Nguyen ◽  
Lin Liu ◽  
...  
Keyword(s):  
Single Cell ◽  
Web Application ◽  
Single Cells ◽  
Drosophila Embryo ◽  
Supplementary Information ◽  
Rna Seq ◽  
Link Type ◽  
Spatial Reconstruction ◽  
Spatial Environment ◽  
Supplementary Material

AbstractMotivationPredicting cell locations is important since with the understanding of cell locations, we may estimate the function of cells and their integration with the spatial environment. Thus, the DREAM Challenge on Single Cell Transcriptomics required participants to predict the locations of single cells in the Drosophila embryo using single cell transcriptomic data.ResultsWe have developed over 50 pipelines by combining different ways of pre-processing the RNA-seq data, selecting the genes, predicting the cell locations, and validating predicted cell locations, resulting in the winning methods for two out of three sub-challenges in the competition. In this paper, we present an R package, SCTCwhatateam, which includes all the methods we developed and the Shiny web-application to facilitate the research on single cell spatial reconstruction. All the data and the example use cases are available in the Supplementary material.AvailabilityThe scripts of the package are available at https://github.com/thanhbuu04/SCTCwhatateam and the Shiny application is available at https://github.com/pvvhoang/[email protected] informationSupplementary data are available at Briefings in Bioinformatics online.

scholarly journals GeneSwitches : Ordering gene-expression and functional events in single-cell experiments

2019 ◽  
Author(s):  
Elaine Y. Cao ◽  
John F. Ouyang ◽  
Owen J.L. Rackham
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Supplementary Information ◽  
Rna Seq ◽  
Link Type ◽  
Statistical Framework ◽  
Changes Over Time ◽  
Over Time

AbstractSummaryEmerging single-cell RNA-seq technologies has made it possible to capture and assess the gene expression of individual cells. Based on the similarity of gene expression profiles, many tools have been developed to generate an in silico ordering of cells in the form of pseudo-time trajectories. However, these tools do not provide a means to find the ordering of critical gene expression changes over pseudo-time. We present GeneSwitches, a tool that takes any single-cell pseudo-time trajectory and determines the precise order of gene-expression and functional-event changes over time. GeneSwitches uses a statistical framework based on logistic regression to identify the order in which genes are either switched on or off along pseudo-time. With this information, users can identify the order in which surface markers appear, investigate how functional ontologies are gained or lost over time, and compare the ordering of switching genes from two related pseudo-temporal processes.AvailabilityGeneSwitches is available at https://geneswitches.ddnetbio.comContactowen.rackham@duke-nus.edu.sgSupplementary Informationis available at http://www.ddnetbio.com/files/GeneSwitches_SI.pdf

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

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.

scholarly journals sepal: identifying transcript profiles with spatial patterns by diffusion-based modeling

2021 ◽  
Author(s):  
Alma Andersson ◽  
Joakim Lundeberg
Keyword(s):  
Spatial Patterns ◽  
Expression Profiles ◽  
Synthetic Data ◽  
Real Data ◽  
Cell Types ◽  
Statistical Hypothesis ◽  
Supplementary Information ◽  
Statistical Hypothesis Testing ◽  
Transcriptomics Data ◽  
Transcript Profiles

Abstract Motivation Collection of spatial signals in large numbers has become a routine task in multiple omics-fields, but parsing of these rich datasets still pose certain challenges. In whole or near-full transcriptome spatial techniques, spurious expression profiles are intermixed with those exhibiting an organized structure. To distinguish profiles with spatial patterns from the background noise, a metric that enables quantification of spatial structure is desirable. Current methods designed for similar purposes tend to be built around a framework of statistical hypothesis testing, hence we were compelled to explore a fundamentally different strategy. Results We propose an unexplored approach to analyze spatial transcriptomics data, simulating diffusion of individual transcripts to extract genes with spatial patterns. The method performed as expected when presented with synthetic data. When applied to real data, it identified genes with distinct spatial profiles, involved in key biological processes or characteristic for certain cell types. Compared to existing methods, ours seemed to be less informed by the genes’ expression levels and showed better time performance when run with multiple cores. Availabilityand implementation Open-source Python package with a command line interface (CLI), freely available at https://github.com/almaan/sepal under an MIT licence. A mirror of the GitHub repository can be found at Zenodo, doi: 10.5281/zenodo.4573237. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals treeclimbR pinpoints the data-dependent resolution of hierarchical hypotheses

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ruizhu Huang ◽  
Charlotte Soneson ◽  
Pierre-Luc Germain ◽  
Thomas S.B. Schmidt ◽  
Christian Von Mering ◽  
...  
Keyword(s):  
Single Cell ◽  
Synthetic Data ◽  
Cell Types ◽  
Data Driven ◽  
Rna Seq ◽  
Hierarchical Trees

AbstracttreeclimbR is for analyzing hierarchical trees of entities, such as phylogenies or cell types, at different resolutions. It proposes multiple candidates that capture the latent signal and pinpoints branches or leaves that contain features of interest, in a data-driven way. It outperforms currently available methods on synthetic data, and we highlight the approach on various applications, including microbiome and microRNA surveys as well as single-cell cytometry and RNA-seq datasets. With the emergence of various multi-resolution genomic datasets, treeclimbR provides a thorough inspection on entities across resolutions and gives additional flexibility to uncover biological associations.

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