cytoKernel: Robust kernel embeddings for assessing differential expression of single cell data.

High-throughput sequencing of single-cell data can be used to rigorously evlauate cell specification and enable intricate variations between groups or conditions. Many popular existing methods for differential expression target differences in aggregate measurements (mean, median, sum) and limit their approaches to detect only global differential changes. We present a robust method for differential expression of single-cell data using a kernel-based score test, cytoKernel.

Fecal microbiota composition, serum metabolomics, and markers of inflammation in dogs fed a raw meat-based diet compared to those on a kibble diet.

Introduction: Despite the potential health risks associated with feeding raw and non-traditional diets, the use of these diets in dogs is increasing, yet the health outcomes associated with these diets is not well understood. This study investigates the effect of feeding dogs a kibble or raw meat-based diets on fecal microbiota composition, serum metabolomics and inflammatory markers.

Methods: Clinically healthy dogs with a history of consuming either kibble (KD,  = 27) or raw meat-based diets (RMBD,  = 28) for more than 1 year were enrolled.

Control of false discoveries in grouped hypothesis testing for eQTL data.

Background: Expression quantitative trait locus (eQTL) analysis aims to detect the genetic variants that influence the expression of one or more genes. Gene-level eQTL testing forms a natural grouped-hypothesis testing strategy with clear biological importance. Methods to control family-wise error rate or false discovery rate for group testing have been proposed earlier, but may not be powerful or easily apply to eQTL data, for which certain structured alternatives may be defensible and may enable the researcher to avoid overly conservative approaches.

Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus.

Introduction: Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%.

Diagnostic utility of ultrasound-guided fine-needle aspiration and needle-core biopsy sampling of canine splenic masses.

This prospective clinical study sought to determine the accuracy of cytopathologic examination and needle-core biopsy (NCB) against diagnoses obtained by excisional histopathology (EH) for canine splenic masses. Twenty-five masses were evaluated by ultrasound-guided fine-needle aspiration (FNA) and NCB tissue sampling. Each spleen was placed in a container and artificial skin placed over its surface.

Healing time of experimentally induced distal limb wounds in horses is not reduced by local injection of equine-origin liquid amnion allograft.

Objective: To assess the efficacy of an equine-origin liquid amnion allograft (ELAA) derived from both amniotic fluid and amniotic membrane on the healing time of experimentally induced distal limb wounds in horses.

Animals: 8 adult horses.

Procedures: On day 0, horses were anesthetized and a 2.

Effect of perfusate volume on amikacin concentrations after saphenous intravenous regional limb perfusion in standing, sedated horses.

Objective: To determine the influence of perfusate volume on synovial fluid amikacin concentrations in the joints of the hind limb after standing saphenous intravenous regional limb perfusion (IVRLP).

Study Design: Randomized crossover design.

Animals: Six adult horses.

Compositional Data Analysis using Kernels in mass cytometry data.

Motivation: Cell-type abundance data arising from mass cytometry experiments are compositional in nature. Classical association tests do not apply to the compositional data due to their non-Euclidean nature. Existing methods for analysis of cell type abundance data suffer from several limitations for high-dimensional mass cytometry data, especially when the sample size is small.

Clinical health markers in dogs fed raw meat-based or commercial extruded kibble diets.

The interest and demand for healthy and less processed foods for human consumption have been mirrored in the pet industry, with an explosion of alternative diets available. Several nontraditional feeding methodologies including raw meat-based diets (RMBDs) are believed by many dog owners to be superior to traditional extruded commercial dog foods. Despite the strong opinions, limited data are available comparing objective health measures among healthy dogs fed using different methods of diet preparation.

Systems genetics analysis of the LXS recombinant inbred mouse strains:Genetic and molecular insights into acute ethanol tolerance.

We have been using the Inbred Long- and Short-Sleep mouse strains (ILS, ISS) and a recombinant inbred panel derived from them, the LXS, to investigate the genetic underpinnings of acute ethanol tolerance which is considered to be a risk factor for alcohol use disorders (AUDs). Here, we have used RNA-seq to examine the transcriptome of whole brain in 40 of the LXS strains 8 hours after a saline or ethanol "pretreatment" as in previous behavioral studies. Approximately 1/3 of the 14,184 expressed genes were significantly heritable and many were unique to the pretreatment.

Insight into genetic regulation of miRNA in mouse brain.

Background: micro RNA (miRNA) are important regulators of gene expression and may influence phenotypes and disease traits. The connection between genetics and miRNA expression can be determined through expression quantitative loci (eQTL) analysis, which has been extensively used in a variety of tissues, and in both human and model organisms. miRNA play an important role in brain-related diseases, but eQTL studies of miRNA in brain tissue are limited.

Minimizing Batch Effects in Mass Cytometry Data.

Cytometry by Time-Of-Flight (CyTOF) uses antibodies conjugated to isotopically pure metals to identify and quantify a large number of cellular features with single-cell resolution. A barcoding approach allows for 20 unique samples to be pooled and processed together in one tube, reducing the intra-barcode technical variability. However, with only 20 samples per barcode, multiple barcode sets (batches) are required to address questions in robustly powered study designs.

Unsupervised discovery of phenotype-specific multi-omics networks.

Motivation: Complex diseases often involve a wide spectrum of phenotypic traits. Better understanding of the biological mechanisms relevant to each trait promotes understanding of the etiology of the disease and the potential for targeted and effective treatment plans. There have been many efforts towards omics data integration and network reconstruction, but limited work has examined the incorporation of relevant (quantitative) phenotypic traits.

SIX2 Mediates Late-Stage Metastasis via Direct Regulation of and Induction of a Cancer Stem Cell Program.

The capacity for tumor cells to metastasize efficiently is directly linked to their ability to colonize secondary sites. Here we identify Six2, a developmental transcription factor, as a critical regulator of a breast cancer stem cell program that enables metastatic colonization. In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs.

Association of genetic polymorphisms in the pore domains of mechano-gated TREK-1 channel with overactive lower urinary tract symptoms in humans.

Aims: Mechanosensitivity of the urinary bladder is regulated by many factors including mechano-gated two-pore domain (K P, KCNK) potassium channels. TWIK-related K channel, TREK-1, is a predominantly expressed member of K P channel family in the human detrusor, and its expression and function are diminished in patients with overactive lower urinary tract symptoms (LUTS). The changes in channel activity may result from spontaneously occurring gene mutations.

Author Correction: Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression.

In the original version of this Article, the title of the legend to Fig. 7 incorrectly read 'Knockdown of B55α increases breast cancer metastasis' instead of 'Knockdown of B55α decreases breast cancer metastasis'. This has now been corrected in both the PDF and HTML versions of the Article.

Predictive modeling of miRNA-mediated predisposition to alcohol-related phenotypes in mouse.

Background: MicroRNAs (miRNAs) are small non-coding RNAs that bind messenger RNAs and promote their degradation or repress their translation. There is increasing evidence of miRNAs playing an important role in alcohol related disorders. However, the role of miRNAs as mediators of the genetic effect on alcohol phenotypes is not fully understood.

miR-MaGiC improves quantification accuracy for small RNA-seq.

Objective: Many tools have been developed to profile microRNA (miRNA) expression from small RNA-seq data. These tools must contend with several issues: the small size of miRNAs, the small number of unique miRNAs, the fact that similar miRNAs can be transcribed from multiple loci, and the presence of miRNA isoforms known as isomiRs. Methods failing to address these issues can return misleading information.

Testing cross-phenotype effects of rare variants in longitudinal studies of complex traits.

Many gene mapping studies of complex traits have identified genes or variants that influence multiple phenotypes. With the advent of next-generation sequencing technology, there has been substantial interest in identifying rare variants in genes that possess cross-phenotype effects. In the presence of such effects, modeling both the phenotypes and rare variants collectively using multivariate models can achieve higher statistical power compared to univariate methods that either model each phenotype separately or perform separate tests for each variant.

Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression.

Eya genes encode a unique family of multifunctional proteins that serve as transcriptional co-activators and as haloacid dehalogenase-family Tyr phosphatases. Intriguingly, the N-terminal domain of Eyas, which does not share sequence similarity to any known phosphatases, contains a separable Ser/Thr phosphatase activity. Here, we demonstrate that the Ser/Thr phosphatase activity of Eya is not intrinsic, but arises from its direct interaction with the protein phosphatase 2A (PP2A)-B55α holoenzyme.

A procedure to detect general association based on concentration of ranks.

In modern high-throughput applications, it is important to identify pairwise associations between variables, and desirable to use methods that are powerful and sensitive to a variety of association relationships. We describe RankCover, a new non-parametric association test of association between two variables that measures the concentration of paired ranked points. Here 'concentration' is quantified using a disk-covering statistic similar to those employed in spatial data analysis.

Impact of Regular Cannabis Use on Biomarkers of Lower Urinary Tract Function.

Objective: To evaluate the differences in the composition and quantities of urine peptides in regular cannabis users and nonusers by liquid chromatography tandem mass spectrometry analysis.

Materials And Methods: Urine specimens from healthy control subjects and cannabis users were utilized to identify the differences in the number and quantity of urine proteins by liquid chromatography tandem mass spectrometry analysis. Significantly altered proteins were determined by a permutation testing statistical method.

Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway.

Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection.