Robust summarization and inference in proteome-wide label-free quantification

Label-Free Quantitative mass spectrometry based workflows for differential expression (DE) analysis of proteins impose important challenges on the data analysis because of peptide-specific effects and context dependent missingness of peptide intensities. Peptide-based workflows, like MSqRob, test for DE directly from peptide intensities and outperform summarization methods which first aggregate MS1 peptide intensities to protein intensities before DE analysis. However, these methods are computationally expensive, often hard to understand for the non-specialized end-user, and do not provide protein summaries, which are important for visualization or downstream processing. In this work, we therefore evaluate state-of-the-art summarization strategies using a benchmark spike-in dataset and discuss why and when these fail compared with the state-of-the-art peptide based model, MSqRob. Based on this evaluation, we propose a novel summarization strategy, MSqRobSum, which estimates MSqRob's model parameters in a two-stage procedure circumventing the drawbacks of peptide-based workflows. MSqRobSum maintains MSqRob's superior performance, while providing useful protein expression summaries for plotting and downstream analysis. Summarizing peptide to protein intensities considerably reduces the computational complexity, the memory footprint and the model complexity, and makes it easier to disseminate DE inferred on protein summaries. Moreover, MSqRobSum provides a highly modular analysis framework, which provides researchers with full flexibility to develop data analysis workflows tailored toward their specific applications

MSqRob takes the missing hurdle : uniting intensity- and count-based proteomics

Missing values are a major issue in quantitative data-dependent mass spectrometry-based proteomics. We therefore present an innovative solution to this key issue by introducing a hurdle model, which is a mixture between a binomial peptide count and a peptide intensity-based model component. It enables dramatically enhanced quantification of proteins with many missing values without having to resort to harmful assumptions for missingness. We demonstrate the superior performance of our method by comparing it with state-of-the-art methods in the field

Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective cross-sectional analysis of CT diagnosed bronchiectatic patients

<p>Abstract</p> <p>Introduction</p> <p>There is a relative lack of information about the death rate and morbidity of non-cystic fibrosis bronchiectasis and most studies are limited due to referral bias. We wanted to assess death rate and morbidity in those patients at our hospital.</p> <p>Methods</p> <p>Adult patients seen at our department between June 2006 and November 2009 were recruited if the key string <it>"bronchiect</it>-" was mentioned in electronic clinical records and if chest CT imaging was available. Clinical records of all patients with confirmed radiologic diagnosis of bronchiectasis were reviewed and clinical characteristics were analyzed.</p> <p>Results</p> <p>539 patients with a radiographic diagnosis of non-cystic fibrosis bronchiectasis were identified in a retrospective cross-sectional analysis giving a prevalence of 2.6% in our hospital population. A wide range of etiologies was found with idiopathic bronchiectasis in 26%. In the 41 months interval, 57 patients (10.6%) died. We found a median exacerbation rate of 1.94 per year. Bacterial colonization status was associated with more deaths, exacerbation rate, symptoms and reduced pulmonary function. Pulmonary hypertension was found in 48% of our patients.</p> <p>Conclusions</p> <p>We evaluated a large non-cystic fibrosis bronchiectasis population, and provided new epidemiological data on associations between clinical characteristics and deaths and morbidity in these patients.</p

A cohort description and analysis of the effect of gabapentin on idiopathic cough

BACKGROUND: Chronic idiopathic cough (known as cough hypersensitivity syndrome) is defined by cough in the absence of an identifiable cause. Gabapentin has been suggested as a treatment but evidence is scarce. The aim of our study was to describe the clinical features of patients with unexplained chronic cough and to investigate the effect of gabapentin (600 mg twice a day for a minimal duration of 4 weeks) in reducing cough symptoms. METHODS: A patient cohort analysis was performed. Patients were retrieved using a query in our medical database for the words ‘cough’ and ‘gabapentin’ in 2011. Patients without a clear etiology of cough despite having performed a stepwise diagnostic approach, were included. Medical records of these patients were analyzed. A telephonic survey was performed and patients were asked to retrospectivally rate their cough when they attended the outpatient clinic. They were then asked to rate their cough after treatment with gabapentin. A scale from one to ten was used to score cough severity. They were also questioned about the triggers inducing cough. To evaluate the cough severity score, the results were correlated with questions of the Leicester Cough Questionnaire. RESULTS: We recruited 51 patients (87% female) with a mean age of onset of 47 years (± 14 y) and an average cough duration of 48 months. The most frequently reported cough triggers included change of temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge to cough was located in the throat area. Thirty-five patients effectively took the prescribed gabapentin. The average improvement in cough score was 2.8/10 (p<0.0001). Of the 35 patients, 20 achieved improvement of their cough symptoms. Responders had a higher pre-treatment cough severity score (p=0.02) and were more likely to have a history of pre-cough airway infection (p=0.04). Current cough severity score negatively correlated with the Leicester Cough Questionnaire scores (p=0.05). CONCLUSION: Chronic idiopathic cough were predominantly middle-aged women, frequently reporting various cough triggers. We also demonstrated that gabapentin can significantly improve cough in these patients. Responders tend to have higher pre-treatment severity scores and have a history of an airway infection