An R script for quality control in genome-wide association studies.

Recent advances in massive genotyping technology based on SNP (Single Nucleotide Polymorphisms) markers are pushing animal breeding research into a new era where the entire genome is screened in the search for genes which affect traits of economic interest, called genome wide association studies (GWAS). The first step in setting up a GWAS is to perform a quality control analysis (QC) on the genotyped data in order to filter out samples and SNPs not satisfying a previously defined set of criteria [1]. The most common criteria include sample and SNP call rate, minor allele frequency (MAF) and Hardy-Weinberg equilibrium (HWE). It is also recommended to analyze the heterozygosity and the presence of population structure and outlier samples. However, a different set of criteria and thresholds may be more appropriate for different datasets. We wrote an R script [2] which implements a number of QC criteria, making them available as functions and allowing users to use those QC criteria which are more appropriate to their dataset. In this work, we describe a set of functions implemented in our R script and illustrate its use in a GWAS of cattle meat quality in a Canchim cattle breed population.X-MEETING 2011

Self-compassion is associated with less stress and depression and greater attention and brain response to affective stimuli in women managers

Abstract Background Women have been assuming more responsibilities and higher positions in major companies, which exposes them to high levels of stress. Higher perceived work stress is related to higher emotional reactivity. Difficulties with emotional regulation can lead to anxiety and mood disorders, which are more prevalent in women than men. Indeed, women leaders are more likely to experience emotional fatigue than men due to excessive empathy. Our aim was to evaluate the associations between self-compassion (SC) scores to depression symptoms, perceived stress and mindfulness, as well as with brain responses to high-arousal unpleasant and pleasant pictures from the International Affective Picture System (IAPS), as measured through functional Magnetic Resonance Imaging (fMRI) in women managers. Methods Forty-six participants were selected for the study. All participants filled the Self Compassion Scale (SCS), Beck Depression Inventory (BDI), Mindful Awareness Attention Scale (MAAS) and the Perceived Stress Scale (PSS). After that they were scanned during an fMRI affective response paradigm. Correlation analysis were performed among these variables. Results Our data suggest that women with higher SC scores respond to affective stimuli with higher activation of the precuneus (a brain region related to self-referential processing), lower levels of stress and depression and show greater attention in everyday activities. Conclusion SC may be an important characteristic for women leaders because of its association with higher sensitivity to emotional stimuli and mindfulness. These skills may allow them to be more aware of others while being less susceptible for stress and depression symptoms

Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC

Introduction: Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized. Methods: In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT. Results: Among 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS). With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, p < 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, p < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, p = 0.009), respectively. Of 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had an improved ORR (53.5% versus 36.4%, p = 0.004), mPFS (10.8 versus 5.5 mo, p < 0.001), and mOS (29.2 versus 13.1 mo, p < 0.001), compared with those with a TMB less than the 90th percentile. In all-comers with nonsquamous NSCLC, the presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all p < 0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring mutations in STK11, KEAP1, or SMARCA4 (all p < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all p < 0.05), but STK11 mutation status had no significant impact on mPFS (p = 0.16) or mOS (p = 0.38). Conclusions: In advanced NSCLC, better patient performance status, low derived neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with improved clinical outcomes to first-line CIT