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How many markers are needed to robustly determine a cell's type?

ABSTRACT: Our understanding of cell types has advanced considerably with the publication of single-cell atlases. Marker genes play an essential role for experimental validation and computational analyses such as physiological characterization, annotation, and deconvolution. However, a framework for quantifying marker replicability and selecting replicable markers is currently lacking. Here, using high-quality data from the Brain Initiative Cell Census Network (BICCN), we systematically investigate marker replicability for 85 neuronal cell types. We show that, due to dataset-specific noise, we need to combine 5 datasets to obtain robust differentially expressed (DE) genes, particularly for rare populations and lowly expressed genes. We estimate that 10 to 200 meta-analytic markers provide optimal downstream performance and make available replicable marker lists for the 85 BICCN cell types. Replicable marker lists condense interpretable and generalizable information about cell types, opening avenues for downstream applications, including cell type annotation, selection of gene panels, and bulk data deconvolution.

SUBMITTER: Fischer S

PROVIDER: S-EPMC8571500 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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How many markers are needed to robustly determine a cell's type?

Fischer Stephan S Gillis Jesse J

iScience 20211014 11

Our understanding of cell types has advanced considerably with the publication of single-cell atlases. Marker genes play an essential role for experimental validation and computational analyses such as physiological characterization, annotation, and deconvolution. However, a framework for quantifying marker replicability and selecting replicable markers is currently lacking. Here, using high-quality data from the Brain Initiative Cell Census Network (BICCN), we systematically investigate marker ...[more]

PMID: 34765918

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Project description:BackgroundInsecticide-treated nets (ITNs) have served as the cornerstone of malaria vector control in sub-Saharan Africa for the past two decades. Over 2.5 billion ITNs have been delivered since 2004 primarily through periodic mass distribution campaigns scheduled at approximately three-year intervals, aligning with the expected lifespan of nets. Recent work indicates that ITN retention times are less than two years in most countries, raising key questions for quantification approaches and delivery frequency for ITN distribution. This paper models several quantification approaches for five typical ITN distribution strategies, estimates the proportion of the population with access to an ITN, and presents recommended quantification approaches to meet global targets for ITN access and use.MethodsA stock and flow model with annual timesteps was used to model ITN distribution and resulting ITN access for 2020-2035 under five scenarios in 40 countries: (1) three-year mass campaigns, (2) full-scale annual continuous distribution, (3) three-year mass campaigns plus continuous distribution in the years between campaigns, (4) three-year mass campaigns at different quantification approaches, (5) two-year mass campaigns at different quantification approaches. All scenarios included ITN distribution to pregnant women at antenatal clinics and infants at immunization visits.ResultsThe current status quo of conducting mass campaigns every three years using a population/1.8 quantifier is insufficient to achieve or maintain targets of 80% population access to ITNs in most malaria-endemic countries, given most estimated retention times are less than three years. Tailored three- or two-year mass campaigns were less efficient than annual continuous distribution strategies in nearly all settings. For countries with at least 2.5 year median ITN retention times, full scale continuous distribution provided better ITN access while needing 20-23% fewer ITNs compared to current mass campaigns.ConclusionGiven variation in ITN retention times across countries, tailored quantification approaches for mass campaigns and continuous distribution strategies are warranted. Continuous distribution strategies are likely to offer more efficient ways to maintain ITN coverage, with fewer nets, where ITN retention times are at least two and a half years. National malaria programmes and their funding partners should work to increase the number of ITNs available to those vulnerable to malaria, while at the same time working to extend the useful life of these critical commodities.

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How many markers are needed to robustly determine a cell's type?

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How many markers are needed to robustly determine a cell's type?

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