NGS allele counts versus called genotypes for testing genetic association.

Unlabelled: RNA sequence data are commonly summarized as read counts. By contrast, so far there is no alternative to genotype calling for investigating the relationship between genetic variants determined by next-generation sequencing (NGS) and a phenotype of interest. Here we propose and evaluate the direct analysis of allele counts for genetic association tests.

RNA Sequencing of Hepatobiliary Cancer Cell Lines: Data and Applications to Mutational and Transcriptomic Profiling.

Cancer cell lines allow the identification of clinically relevant alterations and the prediction of drug response. However, sequencing data for hepatobiliary cancer cell lines in general, and particularly gallbladder cancer (GBC), are sparse. Here, we apply RNA sequencing to characterize 10 GBC, eight hepatocellular carcinoma, and five cholangiocarcinoma (CCA) cell lines.

ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans.

Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence.

Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication.

Locoregional risk assessment after neoadjuvant chemotherapy in patients with primary breast cancer: clinical utility of the CPS + EG score.

Purpose: Locoregional control is a prerequisite to cure primary breast cancer but the prediction of locoregional recurrence to guide further local therapy following neoadjuvant chemotherapy remains a challenge. The CPS + EG score was designed to predict distant recurrences. Here we examine its ability to predict both not only distant but also locoregional recurrences with respect to accuracy and clinical applicability.

Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p.

Gallbladder carcinoma (GBC) is a biliary tract cancer with few treatment options and poor prognosis. Radical surgery is the only potentially curative treatment option but most patients diagnosed with GBC are unresectable. Thus, there is a great need for the development of new treatment options including targeted therapy.

Prediction of local recurrence risk after neoadjuvant chemotherapy in patients with primary breast cancer: Clinical utility of the MD Anderson Prognostic Index.

Background: Locoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI).

Interaction between genetic ancestry and common breast cancer susceptibility variants in Colombian women.

Latino women show lower incidences of breast cancer (BC) than non-Hispanic whites. Large-scale genetic association studies have identified variants robustly associated with BC risk in European women. We examine here the relevance of these variants to Colombian BC and possible interactions with genetic ancestry.

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile.

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death.

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea.

Objective: Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established.

Using next-generation DNA sequence data for genetic association tests based on allele counts with and without consideration of zero inflation.

The relationship between genetic variability and individual phenotypes is usually investigated by testing for association relying on called genotypes. Allele counts obtained from next-generation sequence data could be used for this purpose too. Genetic association can be examined by treating alternative allele counts (AACs) as the response variable in negative binomial regression.

Synergistic activation of phospholipase C-beta3 by Galpha(q) and Gbetagamma describes a simple two-state coincidence detector.

Background: Receptors that couple to G(i) and G(q) often interact synergistically in cells to elicit cytosolic Ca(2+) transients that are several-fold higher than the sum of those driven by each receptor alone. Such synergism is commonly assumed to be complex, requiring regulatory interaction between components, multiple pathways, or multiple states of the target protein.

Results: We show that cellular G(i)-G(q) synergism derives from direct supra-additive stimulation of phospholipase C-beta3 (PLC-beta3) by G protein subunits Gbetagamma and Galpha(q), the relevant components of the G(i) and G(q) signaling pathways.