New computational method unravels single-cell data from multiple people

May 06, 2020

A new computational method for assigning the donor in single cell RNA sequencing experiments provides an accurate way to unravel data from a mixture of people. The Souporcell method, created by Wellcome Sanger Institute researchers and their collaborators could help study how genetic variants in different people affect which genes are expressed during infection or response to drugs.

Published this week in Nature Methods, the software could increase efficiency of single-cell experiments, assisting research into transplants, personalised medicine and malaria.

Single-cell RNA sequencing (RNAseq) can reveal exactly which genes are switched on in each individual cell, revealing cell types and what they do. Pooling multiple people's cells into a single cell RNAseq experiment helps to identify how different genomes affect this gene expression. However it is essential to be able to separate the resulting data by individual, which can be very difficult.

The authors tested Souporcell* against three other computational methods using placental cells, pluripotent stem cell lines** and malaria parasites.

Haynes Heaton, the first author from the Wellcome Sanger Institute, said: "Our method, called Souporcell, is able to separate mixtures of individuals' cells in scRNAseq experiments without knowing each individual's full genome sequence beforehand, unlike previous methods. One of the key features of the method is that it estimates the amount of background RNA from dead cells, which is often referred to as the soup. This then allows the removal of that source of noise, and hence the name Souporcell."

Being able to combine the cells into a single experiment increases the accuracy, enabling more information to be found, and also reduces the cost of these experiments.

Dr Martin Hemberg, a senior author from the Wellcome Sanger Institute, said: "The exact genetic sequence of each person can affect their response to infections, or to drug treatments. The new method enables single cell expression data from multiple people to be analysed, to show links between genotype and phenotype, in diseases and in the presence of drugs. This will have implications for personalised medicine."

In addition, some samples inherently have a mix of cells with different genomes, including samples from transplant patients who have their original cells and cells from the donor, or populations of parasites, such as malaria, from an infected individual.

Dr Mara Lawniczak, a senior author from the Wellcome Sanger Institute, said: "This method is helping us understand malaria. People get infected with multiple strains of malaria at once, but we don't know how these strains are competing with each other to reproduce. To even ask the question we have to be able to split out cells of different malaria strains, and Souporcell is enabling this."
-end-
Notes to editors:

*Souporcell is freely available under an MIT open-source license at https://github.com/wheaton5/souporcell.

**HiPSci cell lines from the Human induced Pluripotent Stem cell initiative https://www.sanger.ac.uk/science/collaboration/hipsci

Publication:

Haynes Heaton et al. (2020) Souporcell: robust clustering of single-cell RNA-seq data by genotype without reference genotypes. Nature Methods. DOI: s41592-020-0820-1

Funding:

This work was supported by Wellcome, the Medical Research Council and other funders. Please see the paper for the full list of funders.

Selected websites:

The Wellcome Sanger Institute


The Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast - we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at http://www.sanger.ac.uk or follow us on Twitter, Facebook, LinkedIn and on our Blog.

About Wellcome

Wellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a politically and financially independent foundation. http://www.wellcome.ac.uk

Wellcome Trust Sanger Institute

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.