A1 Refereed original research article in a scientific journal

ILoReg: a tool for high-resolution cell population identification from single-cell RNA-seq data




AuthorsSmolander Johannes, Junttila Sini, Venäläinen Mikko S, Elo Laura L

PublisherOxford University Press

Publication year2021

JournalBioinformatics

Journal name in sourceBioinformatics (Oxford, England)

Journal acronymBioinformatics

Volume37

Issue8

First page 1107

Last page1114

ISSN1367-4803

eISSN1460-2059

DOIhttps://doi.org/10.1093/bioinformatics/btaa919

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/Publication/51831913


Abstract
Single-cell RNA-seq allows researchers to identify cell populations based on unsupervised clustering of the transcriptome. However, subpopulations can have only subtle transcriptomic differences and the high dimensionality of the data makes their identification challenging.\nWe introduce ILoReg, an R package implementing a new cell population identification method that improves identification of cell populations with subtle differences through a probabilistic feature extraction step that is applied before clustering and visualization. The feature extraction is performed using a novel machine learning algorithm, called iterative clustering projection (ICP), that uses logistic regression and clustering similarity comparison to iteratively cluster data. Remarkably, ICP also manages to integrate feature selection with the clustering through L1-regularization, enabling the identification of genes that are differentially expressed between cell populations. By combining solutions of multiple ICP runs into a single consensus solution, ILoReg creates a representation that enables investigating cell populations with a high resolution. In particular, we show that the visualization of ILoReg allows segregation of immune and pancreatic cell populations in a more pronounced manner compared with current state-of-the-art methods.\nILoReg is available as an R package at https://bioconductor.org/packages/ILoReg.\nSupplementary data are available at Supplementary Information and Supplementary Files 1 and 2.\nMOTIVATION\nRESULTS\nAVAILABILITY\nSUPPLEMENTARY INFORMATION

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