Accurate estimation of cell-type composition from gene expression data.

The rapid development of single-cell transcriptomic technologies has helped uncover the cellular heterogeneity within cell populations. However, bulk RNA-seq continues to be the main workhorse for quantifying gene expression levels due to technical simplicity and low cost. To most effectively extract information from bulk data given the new knowledge gained from single-cell methods, we have developed a novel algorithm to estimate the cell-type composition of bulk data from a single-cell RNA-seq-derived cell-type signature.

GiniClust2: a cluster-aware, weighted ensemble clustering method for cell-type detection.

Single-cell analysis is a powerful tool for dissecting the cellular composition within a tissue or organ. However, it remains difficult to detect rare and common cell types at the same time. Here, we present a new computational method, GiniClust2, to overcome this challenge.

Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity.

MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells.

Assessing Inequality in Transcriptomic Data.

Two studies in this issue of Cell Systems use the Gini index from economics to benchmark and quantify gene expression heterogeneity in single-cell or bulk RNA-seq datasets.

A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing.

Many human cancers are resistant to immunotherapy, for reasons that are poorly understood. We used a genome-scale CRISPR-Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of antitumor immunity. Inactivation of >100 genes-including , , and , which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex-sensitized mouse B16F10 melanoma cells to killing by T cells.

Association of Dermatologist Density With the Volume and Costs of Dermatology Procedures Among Medicare Beneficiaries.

Importance: The persistent shortage of dermatologists in the United States affects access to care and patient outcomes.

Objective: To characterize the effect of geographic variations in dermatologist density on the provision of dermatology procedures within Medicare.

Design, Setting, And Participants: This was a cross-sectional study using the 2013 Medicare Provider Utilization and Payment Database.

Recent progress in single-cell cancer genomics.

The advent of single-cell sequencing has been revolutionary to the field of cancer genomics. Perfectly suited to capture cancer's heterogeneous nature, single-cell analyses provide information bulk sequencing could never hope to uncover. Many mechanisms of cancer have yet to be fully understood, and single-cell approaches are showing promise in their abilities to uncover these mysteries.

Pediatric eosinophilic esophagitis is associated with changes in esophageal microRNAs.

The incidence of eosinophilic esophagitis (EoE) has increased in the past several years, yet our understanding of its pathogenesis remains limited. To test the hypothesis that microRNAs (miRNAs) are altered in children with EoE, miRNAs were profiled in esophageal mucosa biopsies obtained from patients with active disease (n = 5) and healthy control subjects (n = 6). Fourteen miRNAs were significantly altered between groups; four of these miRNAs were decreased in EoE patients.

Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon.

Background And Aims: Changes in intestinal microRNAs have been reported in adult patients with ulcerative colitis or Crohn's disease. The goal of this study was to identify changes in microRNA expression associated with colitis in children with inflammatory bowel disease.

Methods: Rectal mucosal biopsies (n = 50) and blood samples (n = 47) were collected from patients with known or suspected inflammatory bowel disease undergoing endoscopy.