scholarly journals Per-sample standardization and asymmetric winsorization lead to accurate clustering of RNA-seq expression profiles

Author(s):  
Davide Risso ◽  
Stefano Maria Pagnotta

Abstract Motivation Data transformations are an important step in the analysis of RNA-seq data. Nonetheless, the impact of transformation on the outcome of unsupervised clustering procedures is still unclear. Results Here, we present an Asymmetric Winsorization per Sample Transformation (AWST), which is robust to data perturbations and removes the need for selecting the most informative genes prior to sample clustering. Our procedure leads to robust and biologically meaningful clusters both in bulk and in single-cell applications. Availability The AWST method is available at https://github.com/drisso/awst. The code to reproduce the analyses is available at https://github.com/drisso/awst\_analysis. Supplementary information Supplementary data are available at Bioinformatics online.

2020 ◽  
Author(s):  
Davide Risso ◽  
Stefano M. Pagnotta

AbstractMotivationData transformations are an important step in the analysis of RNA-seq data. Nonetheless, the impact of transformations on the outcome of unsupervised clustering procedures is still unclear.ResultsHere, we present an Asymmetric Winsorization per Sample Transformation (AWST), which is robust to data perturbations and removes the need for selecting the most informative genes prior to sample clustering. Our procedure leads to robust and biologically meaningful clusters both in bulk and in single-cell applications.AvailabilityThe AWST method is available at https://github.com/drisso/awst. The code to reproduce the analyses is available at https://github.com/drisso/awst_analysis.


2017 ◽  
Author(s):  
Zhun Miao ◽  
Ke Deng ◽  
Xiaowo Wang ◽  
Xuegong Zhang

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.


2020 ◽  
Vol 36 (18) ◽  
pp. 4810-4812
Author(s):  
Qingxi Meng ◽  
Idoia Ochoa ◽  
Mikel Hernaez

Abstract Motivation Sequencing data are often summarized at different annotation levels for further analysis, generally using the general feature format (GFF) or its descendants, gene transfer format (GTF) and GFF3. Existing utilities for accessing these files, like gffutils and gffread, do not focus on reducing the storage space, significantly increasing it in some cases. We propose GPress, a framework for querying GFF files in a compressed form. GPress can also incorporate and compress expression files from both bulk and single-cell RNA-Seq experiments, supporting simultaneous queries on both the GFF and expression files. In brief, GPress applies transformations to the data which are then compressed with the general lossless compressor BSC. To support queries, GPress compresses the data in blocks and creates several index tables for fast retrieval. Results We tested GPress on several GFF files of different organisms, and showed that it achieves on average a 61% reduction in size with respect to gzip (the current de facto compressor for GFF files) while being able to retrieve all annotations for a given identifier or a range of coordinates in a few seconds (when run in a common laptop). In contrast, gffutils provides faster retrieval but doubles the size of the GFF files. When additionally linking an expression file, we show that GPress can reduce its size by more than 68% when compared to gzip (for both bulk and single-cell RNA-Seq experiments), while still retrieving the information within seconds. Finally, applying BSC to the data streams generated by GPress instead of to the original file shows a size reduction of more than 44% on average. Availability and implementation GPress is freely available at https://github.com/qm2/gpress. Supplementary information Supplementary data are available at Bioinformatics online.


2019 ◽  
Vol 35 (21) ◽  
pp. 4472-4473 ◽  
Author(s):  
Páll Melsted ◽  
Vasilis Ntranos ◽  
Lior Pachter

Abstract Summary We introduce the Barcode-UMI-Set format (BUS) for representing pseudoalignments of reads from single-cell RNA-seq experiments. The format can be used with all single-cell RNA-seq technologies, and we show that BUS files can be efficiently generated. BUStools is a suite of tools for working with BUS files and facilitates rapid quantification and analysis of single-cell RNA-seq data. The BUS format therefore makes possible the development of modular, technology-specific and robust workflows for single-cell RNA-seq analysis. Availability and implementation http://BUStools.github.io/ and http://pachterlab.github.io/kallisto/singlecell.html. Supplementary information Supplementary data are available at Bioinformatics online.


2019 ◽  
Vol 35 (22) ◽  
pp. 4757-4759 ◽  
Author(s):  
Vivek Bhardwaj ◽  
Steffen Heyne ◽  
Katarzyna Sikora ◽  
Leily Rabbani ◽  
Michael Rauer ◽  
...  

Abstract Summary Due to the rapidly increasing scale and diversity of epigenomic data, modular and scalable analysis workflows are of wide interest. Here we present snakePipes, a workflow package for processing and downstream analysis of data from common epigenomic assays: ChIP-seq, RNA-seq, Bisulfite-seq, ATAC-seq, Hi-C and single-cell RNA-seq. snakePipes enables users to assemble variants of each workflow and to easily install and upgrade the underlying tools, via its simple command-line wrappers and yaml files. Availability and implementation snakePipes can be installed via conda: `conda install -c mpi-ie -c bioconda -c conda-forge snakePipes’. Source code (https://github.com/maxplanck-ie/snakepipes) and documentation (https://snakepipes.readthedocs.io/en/latest/) are available online. Supplementary information Supplementary data are available at Bioinformatics online.


2020 ◽  
Author(s):  
Ye Yuan ◽  
Ziv Bar-Joseph

AbstractMotivationTime-course gene expression data has been widely used to infer regulatory and signaling relationships between genes. Most of the widely used methods for such analysis were developed for bulk expression data. Single cell RNA-Seq (scRNA-Seq) data offers several advantages including the large number of expression profiles available and the ability to focus on individual cells rather than averages. However, this data also raises new computational challenges.ResultsUsing a novel encoding for scRNA-Seq expression data we develop deep learning methods for interaction prediction from time-course data. Our methods use a supervised framework which represents the data as a 3D tensor and train convolutional and recurrent neural networks (CNN and RNN) for predicting interactions. We tested our Time-course Deep Learning (TDL) models on five different time series scRNA-Seq datasets. As we show, TDL can accurately identify causal and regulatory gene-gene interactions and can also be used to assign new function to genes. TDL improves on prior methods for the above tasks and can be generally applied to new time series scRNA-Seq data.Availability and ImplementationFreely available at https://github.com/xiaoyeye/[email protected] informationSupplementary data are available at XXX online.


2020 ◽  
Vol 36 (11) ◽  
pp. 3588-3589 ◽  
Author(s):  
Kaiyi Zhu ◽  
Dimitris Anastassiou

Abstract Summary We developed 2DImpute, an imputation method for correcting false zeros (known as dropouts) in single-cell RNA-sequencing (scRNA-seq) data. It features preventing excessive correction by predicting the false zeros and imputing their values by making use of the interrelationships between both genes and cells in the expression matrix. We showed that 2DImpute outperforms several leading imputation methods by applying it on datasets from various scRNA-seq protocols. Availability and implementation The R package of 2DImpute is freely available at GitHub (https://github.com/zky0708/2DImpute). Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.


Author(s):  
Andrew E Teschendorff ◽  
Alok K Maity ◽  
Xue Hu ◽  
Chen Weiyan ◽  
Matthias Lechner

Abstract Motivation An important task in the analysis of single-cell RNA-Seq data is the estimation of differentiation potency, as this can help identify stem-or-multipotent cells in non-temporal studies or in tissues where differentiation hierarchies are not well established. A key challenge in the estimation of single-cell potency is the need for a fast and accurate algorithm, scalable to large scRNA-Seq studies profiling millions of cells. Results Here, we present a single-cell potency measure, called Correlation of Connectome and Transcriptome (CCAT), which can return accurate single-cell potency estimates of a million cells in minutes, a 100-fold improvement over current state-of-the-art methods. We benchmark CCAT against 8 other single-cell potency models and across 28 scRNA-Seq studies, encompassing over 2 million cells, demonstrating comparable accuracy than the current state-of-the-art, at a significantly reduced computational cost, and with increased robustness to dropouts. Availability and implementation CCAT is part of the SCENT R-package, freely available from https://github.com/aet21/SCENT. Supplementary information Supplementary data are available at Bioinformatics online.


Author(s):  
Krzysztof Polański ◽  
Matthew D Young ◽  
Zhichao Miao ◽  
Kerstin B Meyer ◽  
Sarah A Teichmann ◽  
...  

Abstract Motivation Increasing numbers of large scale single cell RNA-Seq projects are leading to a data explosion, which can only be fully exploited through data integration. A number of methods have been developed to combine diverse datasets by removing technical batch effects, but most are computationally intensive. To overcome the challenge of enormous datasets, we have developed BBKNN, an extremely fast graph-based data integration algorithm. We illustrate the power of BBKNN on large scale mouse atlasing data, and favourably benchmark its run time against a number of competing methods. Availability and implementation BBKNN is available at https://github.com/Teichlab/bbknn, along with documentation and multiple example notebooks, and can be installed from pip. Supplementary information Supplementary data are available at Bioinformatics online.


2019 ◽  
Author(s):  
Elaine Y. Cao ◽  
John F. Ouyang ◽  
Owen J.L. Rackham

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


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