Simulating paired and longitudinal single-cell RNA sequencing data with rescueSim.

Motivation: As single-cell RNA-sequencing (scRNA-seq) becomes more widely used in transcriptomic research, complex experimental designs, such as paired or longitudinal studies, become increasingly feasible. Paired/longitudinal scRNA-seq enables the study of transcriptomic changes over time within specific cell types, yet guidance on analytical approaches and resources for study planning, such as power analysis, remains limited. Data simulation is a valuable tool for evaluating analysis method performance and informing study design decisions, including sample size selection.

Spatial Heterogeneity of Macrophages in the Human Lung.

Rationale: Transcriptionally-defined populations of interstitial macrophages (IMs) and airspace macrophages (AMs) have recently been identified in the human lung. However, the anatomic locations occupied by these populations (i.e.

Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiology of (), which may enable the pathogen to withstand treatment. While antibiotic-treated has been evaluated in experiments it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affects physiologic processes differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4 weeks of treatment with three sterilizing and three non-sterilizing antibiotics.

Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiologic state of () which may enable the pathogen to withstand treatment. While antibiotic-treated have been evaluated in short-term experiments, it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affect physiologic states differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4-week treatment with three sterilizing and three non-sterilizing antibiotics.

Transcriptional adaptation of that survives prolonged multi-drug treatment in mice.

A major reason that curing tuberculosis requires prolonged treatment is that drug exposure changes bacterial phenotypes. The physiologic adaptations of that survive drug exposure have been obscure due to low sensitivity of existing methods in drug-treated animals. Using the novel SEARCH-TB RNA-seq platform, we elucidated phenotypes in mice treated for with the global standard 4-drug regimen and compared them with the effect of the same regimen .

A comparison of methods for multiple degree of freedom testing in repeated measures RNA-sequencing experiments.

Background: As the cost of RNA-sequencing decreases, complex study designs, including paired, longitudinal, and other correlated designs, become increasingly feasible. These studies often include multiple hypotheses and thus multiple degree of freedom tests, or tests that evaluate multiple hypotheses jointly, are often useful for filtering the gene list to a set of interesting features for further exploration while controlling the false discovery rate. Though there are several methods which have been proposed for analyzing correlated RNA-sequencing data, there has been little research evaluating and comparing the performance of multiple degree of freedom tests across methods.

Comparison of single time-point [111-In] pentetreotide SPECT/CT with dual time-point imaging of neuroendocrine tumors.

Purpose: to determine whether single time-point single-photon emission computed tomography-computed tomography (SPECT/CT) somatostatin receptor imaging can replace traditional dual time-point planar and SPECT somatostatin receptor scintigraphy for evaluation of neuroendocrine tumors.

Materials And Methods: twenty-four patients (9 males, 15 females; mean age: 56 years; range: 14-82 years) underwent [111-In] pentetreotide scintigraphy, with planar whole-body images acquired at 24 and 48 hours after injection and abdominal SPECT/CT at 24 hours postinjection. Two blinded readers independently interpreted each study, using single time-point (24 hours planar and SPECT/CT) and separately using dual time-point (24- and 48-hours planar, and 24-hour SPECT without CT) image information.