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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 |

REPOSITORIES: biostudies-literature

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

Project description:[This corrects the article DOI: 10.1016/j.isci.2021.103292.].

| S-EPMC8786641 | biostudies-literature

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| S-EPMC8179311 | biostudies-literature

How Many Genes are Needed to Resolve Phylogenetic Incongruence?

Project description:The question how many genes are needed to resolve phylogenetic incongruence has been investigated at various taxonomic levels, yet few studies have investigated the minimum required numbers of selected genes based on single-gene tree performance at the genus level or lower. We conducted resampling analyses by compiling transcriptome-based single-copy nuclear gene sequences of 11 species of Primulina (Gesneriaceae) to investigate the minimum numbers of both random and selected genes needed to resolve the phylogeny. Only 8 of the 26 selected genes were sufficient for full resolution, while 175 genes were needed if all 830 random genes were used. Our results provided a baseline for future sampling strategies of gene numbers in molecular phylogenetic studies of speciose taxa. The gene selection strategies based on single-gene tree performance are strongly recommended in phylogenic analyses.

| S-EPMC4533847 | biostudies-other

Assessment of maximal handgrip strength: how many attempts are needed?

Project description:Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS.Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t-test, intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed.Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland-Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender-specific cut-off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle-aged and older populations.Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle-aged and older populations.

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| S-EPMC5916645 | biostudies-literature

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| S-EPMC6580710 | biostudies-literature

Single-particle imaging by x-ray free-electron lasers-How many snapshots are needed?

Project description:X-ray free-electron lasers (XFELs) open the possibility of obtaining diffraction information from a single biological macromolecule. This is because XFELs can generate extremely intense x-ray pulses that are so short that diffraction data can be collected before the sample is destroyed. By collecting a sufficient number of single-particle diffraction patterns, the three-dimensional electron density of a molecule can be reconstructed ab initio. The quality of the reconstruction depends largely on the number of patterns collected at the experiment. This paper provides an estimate of the number of diffraction patterns required to reconstruct the electron density at a targeted spatial resolution. This estimate is verified by simulations for realistic x-ray fluences, repetition rates, and experimental conditions available at modern XFELs. Employing the bacterial phytochrome as a model system, we demonstrate that sub-nanometer resolution is within reach.

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Project description:Amidst the COVID-19 pandemic, clinicians have been plagued with dilemmas related to the uncertainty about diagnostic testing for the virus. It has become commonplace for a patient under investigation (PUI) to repeatedly test negative but have imaging findings that are consistent with COVID-19. This raises the question of when the treating team should entertain alternative diagnoses. We present such a case to help provide a framework for how to weigh repeatedly negative test results in clinical decision making when there is ongoing concern for COVID-19.

| S-EPMC7434325 | biostudies-literature

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Project description:BackgroundAverage real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information.MethodsARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (?80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results.ResultsIn the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality.ConclusionsForty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information.

| S-EPMC3848629 | biostudies-literature

Mentally Sick or Not-(Bio)Markers of Psychiatric Disorders Needed.

Project description:Psychiatric disorders, also called mental illnesses or mental disorders, constitute a wide group of disorders including major depression disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ) and other psychoses, anxiety disorders (ANX), substance-related disorders (SRD), dementia, developmental disorders e [...].

| S-EPMC7465438 | biostudies-literature

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