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Background Rare cell subtypes can profoundly impact the course of human health and disease, yet their presence within a sample is often missed with bulk molecular analysis. Single-cell analysis tools such as FACS, FISH-FC and single-cell barcode-based sequencing can investigate cellular heterogeneity; however, they have significant limitations that impede their ability to identify and transcriptionally...
Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of the serotonin receptor HTR7 as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1,...
Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the “atopic march.” Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march...
The sensation of hunger after a period of fasting and of satiety after eating is crucial to behavioral regulation of food intake, but the biological mechanisms regulating these sensations are incompletely understood. We studied the behavioral and physiological adaptations to fasting in the vinegar fly (Drosophila melanogaster). Here we show that both male and female flies increased their rate of food...
Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans do show similar artifacts, which might affect subsequent analysis. We developed a tool, Harshlight, for the detection and masking of blemishes in HDONA microarray chips. Harshlight uses a combination of statistic...
It is rare that a single gene is sufficient to represent all aspects of genomic activity. Similarly, most common diseases cannot be explained by a mutations at a single locus. Since complex systems tend to be neither linear nor hierarchical in nature, but to have correlated components of unknown relative importance, the assumptions of traditional (parametric) multivariate statistical methods can rarely...
Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans do show similar artifacts, which might affect subsequent analysis. We developed a tool, Harshlight, for the detection and masking of blemishes in HDONA microarray chips. Harshlight uses a combination of statistic...
It is rare that a single gene is sufficient to represent all aspects of genomic activity. Similarly, most common diseases cannot be explained by a mutations at a single locus. Since complex systems tend to be neither linear nor hierarchical in nature, but to have correlated components of unknown relative importance, the assumptions of traditional (parametric) multivariate statistical methods can rarely...
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