A rank-based marker selection method for high throughput scRNA-seq data

Abstract Background High throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of ge...

Full description

Bibliographic Details
Main Authors: Alexander H. S. Vargo, Anna C. Gilbert
Format: Article
Language:English
Published: BMC 2020-10-01
Series:BMC Bioinformatics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12859-020-03641-z
_version_ 1818655294823071744
author Alexander H. S. Vargo
Anna C. Gilbert
author_facet Alexander H. S. Vargo
Anna C. Gilbert
author_sort Alexander H. S. Vargo
collection DOAJ
description Abstract Background High throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of genetic markers that can identify specific cell populations is thus one of the major objectives of computational analysis of mRNA counts data. Many tools have been developed for marker selection on single cell data; most of them, however, are based on complex statistical models and handle the multi-class case in an ad-hoc manner. Results We introduce RankCorr, a fast method with strong mathematical underpinnings that performs multi-class marker selection in an informed manner. RankCorr proceeds by ranking the mRNA counts data before linearly separating the ranked data using a small number of genes. The step of ranking is intuitively natural for scRNA-seq data and provides a non-parametric method for analyzing count data. In addition, we present several performance measures for evaluating the quality of a set of markers when there is no known ground truth. Using these metrics, we compare the performance of RankCorr to a variety of other marker selection methods on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells. Conclusions According to the metrics introduced in this work, RankCorr is consistently one of most optimal marker selection methods on scRNA-seq data. Most methods show similar overall performance, however; thus, the speed of the algorithm is the most important consideration for large data sets (and comparing the markers selected by several methods can be fruitful). RankCorr is fast enough to easily handle the largest data sets and, as such, it is a useful tool to add into computational pipelines when dealing with high throughput scRNA-seq data. RankCorr software is available for download at https://github.com/ahsv/RankCorr with extensive documentation.
first_indexed 2024-12-17T03:07:25Z
format Article
id doaj.art-2b90c0814b264a37b75aa3866d26fe7b
institution Directory Open Access Journal
issn 1471-2105
language English
last_indexed 2024-12-17T03:07:25Z
publishDate 2020-10-01
publisher BMC
record_format Article
series BMC Bioinformatics
spelling doaj.art-2b90c0814b264a37b75aa3866d26fe7b2022-12-21T22:05:55ZengBMCBMC Bioinformatics1471-21052020-10-0121115110.1186/s12859-020-03641-zA rank-based marker selection method for high throughput scRNA-seq dataAlexander H. S. Vargo0Anna C. Gilbert1Department of Mathematics, University of MichiganDepartment of Mathematics, Yale UniversityAbstract Background High throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of genetic markers that can identify specific cell populations is thus one of the major objectives of computational analysis of mRNA counts data. Many tools have been developed for marker selection on single cell data; most of them, however, are based on complex statistical models and handle the multi-class case in an ad-hoc manner. Results We introduce RankCorr, a fast method with strong mathematical underpinnings that performs multi-class marker selection in an informed manner. RankCorr proceeds by ranking the mRNA counts data before linearly separating the ranked data using a small number of genes. The step of ranking is intuitively natural for scRNA-seq data and provides a non-parametric method for analyzing count data. In addition, we present several performance measures for evaluating the quality of a set of markers when there is no known ground truth. Using these metrics, we compare the performance of RankCorr to a variety of other marker selection methods on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells. Conclusions According to the metrics introduced in this work, RankCorr is consistently one of most optimal marker selection methods on scRNA-seq data. Most methods show similar overall performance, however; thus, the speed of the algorithm is the most important consideration for large data sets (and comparing the markers selected by several methods can be fruitful). RankCorr is fast enough to easily handle the largest data sets and, as such, it is a useful tool to add into computational pipelines when dealing with high throughput scRNA-seq data. RankCorr software is available for download at https://github.com/ahsv/RankCorr with extensive documentation.http://link.springer.com/article/10.1186/s12859-020-03641-zSingle cell RNA-seqMarker selectionMachine learningData analysisAlgorithmsBenchmarking
spellingShingle Alexander H. S. Vargo
Anna C. Gilbert
A rank-based marker selection method for high throughput scRNA-seq data
BMC Bioinformatics
Single cell RNA-seq
Marker selection
Machine learning
Data analysis
Algorithms
Benchmarking
title A rank-based marker selection method for high throughput scRNA-seq data
title_full A rank-based marker selection method for high throughput scRNA-seq data
title_fullStr A rank-based marker selection method for high throughput scRNA-seq data
title_full_unstemmed A rank-based marker selection method for high throughput scRNA-seq data
title_short A rank-based marker selection method for high throughput scRNA-seq data
title_sort rank based marker selection method for high throughput scrna seq data
topic Single cell RNA-seq
Marker selection
Machine learning
Data analysis
Algorithms
Benchmarking
url http://link.springer.com/article/10.1186/s12859-020-03641-z
work_keys_str_mv AT alexanderhsvargo arankbasedmarkerselectionmethodforhighthroughputscrnaseqdata
AT annacgilbert arankbasedmarkerselectionmethodforhighthroughputscrnaseqdata
AT alexanderhsvargo rankbasedmarkerselectionmethodforhighthroughputscrnaseqdata
AT annacgilbert rankbasedmarkerselectionmethodforhighthroughputscrnaseqdata