High-accuracy peak picking of proteomics data

A new peak picking algorithm for the analysis of mass spectrometric (MS) data is presented. It is independent of the underlying machine or ionization method, and is able to resolve highly convoluted and asymmetric signals. The method uses the multiscale nature of spectrometric data by first detecting the mass peaks in the wavelet-transformed signal before a given asymmetric peak function is fitted to the raw data. In an optional third stage, the resulting fit can be further improved using techniques from nonlinear optimization. In contrast to currently established techniques (e.g. SNAP, Apex) our algorithm is able to separate overlapping peaks of multiply charged peptides in ESI-MS data of low resolution. Its improved accuracy with respect to peak positions makes it a valuable preprocessing method for MS-based identification and quantification experiments. The method has been validated on a number of different annotated test cases, where it compares favorably in both runtime and accuracy with currently established techniques. An implementation of the algorithm is freely available in our open source framework OpenMS (www.open-ms.de)

peak picking und map alignment

We study two fundamental processing steps in mass spectrometric data analysis from a theoretical and practical point of view. For the detection and extraction of mass spectral peaks we developed an efficient peak picking algorithm that is independent of the underlying machine or ionization method, and is able to resolve highly convoluted and asymmetric signals. The method uses the multiscale nature of spectrometric data by first detecting the mass peaks in the wavelet-transformed signal before a given asymmetric peak function is fitted to the raw data. In two optional stages, highly overlapping peaks can be separated or all peak parameters can be further improved using techniques from nonlinear optimization. In contrast to currently established techniques, our algorithm is able to separate overlapping peaks of multiply charged peptides in LC-ESI-MS data of low resolution. Furthermore, applied to high-quality MALDI-TOF spectra it yields a high degree of accuracy and precision and compares very favorably with the algorithms supplied by the vendor of the mass spectrometers. On the high-resolution MALDI spectra as well as on the low-resolution LC-MS data set, our algorithm achieves a fast runtime of only a few seconds. Another important processing step that can be found in every typical protocol for labelfree quantification is the combination of results from multiple LC-MS experiments to improve confidence in the obtained measurements or to compare results from different samples. To do so, a multiple alignment of the LC-MS maps needs to be estimated. The alignment has to correct for variations in mass and elution time which are present in all mass spectrometry experiments. For the first time we formally define the multiple LC-MS raw and feature map alignment problem using our own distance function for LC-MS maps. Furthermore, we present a solution to this problem. Our novel algorithm aligns LC-MS samples and matches corresponding ion species across samples. In a first step, it uses an adapted pose clustering approach to efficiently superimpose raw maps as well as feature maps. This is done in a star-wise manner, where the elements of all maps are transformed onto the coordinate system of a reference map. To detect and combine corresponding features in multiple feature maps into a so-called consensus map, we developed an additional step based on techniques from computational geometry. We show that our alignment approach is fast and reliable as compared to five other alignment approaches. Furthermore, we prove its robustness in the presence of noise and its ability to accurately align samples with only few common ion species.Im Rahmen dieser Arbeit beschäftigen wir uns mit peak picking und map alignment; zwei fundamentalen Prozessierungsschritten bei der Analyse massenspektrometrischer Signale. Im Gegensatz zu vielen anderen peak picking Ansätzen haben wir einen Algorithmus entwickelt, der alle relevanten Informationen aus den massenspektrometrischen Peaks extrahiert und unabhängig von der analytischen Fragestellung und dem MS Instrument ist. Im ersten Teil dieser Arbeit stellen wir diesen generischen peak picking Algorithmus vor. Für die Detektion der Peaks nutzen wir die Multiskalen-Natur von MS Messungen und erlauben mit einem Wavelet-basierten Ansatz auch das Prozessieren von stark verrauschten und Baseline-behafteten Massenspektren. Neben der exakten m/z Position und dem FWHM Wert eines Peaks werden seine maximale Intensität sowie seine Gesamtintensität bestimmt. Mithilfe des Fits einer analytischen Peakfunktion extrahieren wir außerdem zusätzliche Informationen über die Peakform. Zwei weiterere optionale Schritte ermöglichen zum einen die Trennung stark überlappender Peaks sowie die Optimierung der berechneten Peakparameter. Anhand eines niedrig aufgelösten LC-ESI-MS Datensatzes sowie eines hoch aufgelösten MALDI-MS Datensatzes zeigen wir die Effizienz unseres generischen Algorithmus sowie seine schnelle Laufzeit im Vergleich mit kommerziellen peak picking Algorithmen. Ein direkter quantitativer Vergleich mehrer LC-MS Messungen setzt voraus, dass Signale des gleichen Peptids innerhalb unterschiedlicher Maps die gleichen RT und m/z Positionen besitzen. Aufgrund experimenteller Unsicherheiten sind beide Dimension verzerrt. Unabhängig vom Prozessierungsstand der LC-MS Maps müssen die Verzerrungen vor einem Vergleich der Maps korrigiert werden. Mithilfe eines eigens entwickelten Ähnlichkeitsmaßes für LC-MS Maps entwickeln wir die erste formale Definition des multiplen LC-MS Roh- und Featuremap Alignment Problems. Weiterhin stellen wir unseren geometrischen Ansatz zur Lösung des Problems vor. Durch die Betrachtung der LC-MS Maps als zwei-dimensionale Punktmengen ist unser Algorithmus unabhängig vom Prozessierungsgrad der Maps. Wir verfolgen einen sternförmigen Alignmentansatz, bei dem alle Maps auf eine Referenzmap abgebildet werden. Die Überlagerung der Maps erfolgt hierbei mithilfe eines pose clustering basierten Algorithmus. Diese Überlagerung der Maps löst bereits das Rohmap Alignment Problem. Zur Lösung des multiplen Featuremap Alignment Problems implementieren wir einen zusätzlichen, effizienten Gruppierungsschritt, der zusammengehörige Peptidsignale in unterschiedlichen Maps einander zuordnet. Wir zeigen die Effizienz und Robustheit unseres Ansatzes auf zwei realen sowie auf drei künstlichen Datensätzen. Wir vergleichen hierbei die Güte sowie die Laufzeit unseres Algorithmus mit fünf weiteren frei verfügbaren Featuremap-Alignmentmethoden. In allen Experimenten überzeugte unser Algorithmus mit einer schnellen Laufzeit und den besten recall Werten

Ritualepisoden. Das Sedfest-Tor Osorkons II. in Bubastis

Eine Untersuchung zum königlichen Ritual des sogenannten Sedfestes im Alten Ägypten anhand der Sedfestreliefs vom Torbau Osorkons II. in Bubastis

EuroQoL in assessment of the effect of pulmonary rehabilitation COPD patients

SummaryBackgroundThe effect of pulmonary rehabilitation on EuroQol in COPD patients has not been investigated previously.Methods/materialsTwo hundred and twenty nine consecutive COPD patients who had completed a 7-week pulmonary rehabilitation programme were assessed with EuroQol five-dimension questionnaire (EQ-5D), endurance shuttle walk test (ESWT), and the St George's Respiratory Questionnaire (SGRQ) before and after the programme, and at the 3-month follow-up visit.ResultsTwo hundred and two (88.4%) patients had FEV1<50% predicted and all but four (1.7%) had dyspnoea score at least 3 on MRC scale. At completion of the programme, statistical significant improvements were seen for ESWT 157.3s; p<0.001, EQ-5D utility score −0.019; p=0.03, EQ-5D VAS −2.1; p=0.056, SGRQ total score −2.8units; p<0.001. The effects of rehabilitation on ESWT and SGRQ were maintained at 3-month follow-up (158.9s and −2.9units), while the effect on EQ-5 utility decreased (0.013; p=0.18). At baseline, there was a maximum score (“ceiling effect”) for EQ-5D utility and EQ VAS in 29 (12.7%) and five (2.2%) of the patients, respectively. After rehabilitation these number increased to 41 (17.9%) and seven (3.1%).ConclusionsIn COPD patients receiving rehabilitation, responsiveness of EQ-5D utility was poor. One explanation might be a “ceiling effect” of this instrument

Equilibria of oligomeric proteins under high pressure – A theoretical description

High pressure methods have become a useful tool for studying protein structure and stability. Using them, various physico-chemical processes including protein unfolding, aggregation, oligomer dissociation or enzyme-activity decrease were studied on many different proteins. Oligomeric protein dissociation is a process that can perfectly utilize the potential of high-pressure techniques, as the high pressure shifts the equilibria to higher concentrations making them better observable by spectroscopic methods. This can be especially useful when the oligomeric form is highly stable at atmospheric pressure. These applications may be, however, hindered by less intensive experimental response as well as interference of the oligomerization equilibria with unfolding or aggregation of the subunits, but also by more complex theoretical description. In this study we develop mathematical models describing different kinds of oligomerization equilibria, both closed (equilibrium of monomer and the highest possible oligomer without any intermediates) and consecutive. Closed homooligomer equilibria are discussed for any oligomerization degree, while the more complex heterooligomer equilibria and the consecutive equilibria in both homo- and heterooligomers are taken into account only for dimers and trimers. In all the cases, fractions of all the relevant forms are evaluated as functions of pressure and concentration. Significant points (inflection points and extremes) of the resulting transition curves, that can be determined experimentally, are evaluated as functions of pressure and/or concentration. These functions can be further used in order to evaluate the thermodynamic parameters of the system, i.e. atmospheric-pressure equilibrium constants and volume changes of the individual steps of the oligomer-dissociation processes. © 2016 Elsevier LtdP208-12-G016, GACR, Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P208-12-G016

Using a multi-level tailored design process to develop a customer satisfaction survey for university evaluation

A multi-level procedure is described in order to develop a total quality management survey tool in the field of engineering academia. As a first step a review of available evaluation tools for universities is conducted, resulting in over 150 items used for evaluation purposes. Secondly all dimensions of educational evaluation used in previous research are summarized, resulting in 15 dimensions. In a third step, items are assigned to the dimensions, overlapping items were combined or removed, and item content and dimensions were adjusted to the specific conditions of the target faculty. Fourthly, the resulting twelve dimensions were used in first, investigative interviews in the target population. Results indicate that eleven dimensions sufficiently mapped all aspects of evaluation. After revising the items to improve understanding in a fifth step cognitive pretests were conducted. The final revision resulted in 83 items assigned to eleven dimensions

Home-based exercise and support programme for people with dementia and their caregivers: study protocol of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Dementia affects the mood of people with dementia but also of their caregivers. In the coming years, the number of people with dementia will increase worldwide and most of them will continue to live in the community as long as possible. Home-based psychosocial interventions reducing the depressive symptoms of both people with dementia and their caregivers in their own home are highly needed.</p> <p>Methods/Design</p> <p>This manuscript describes the design of a Randomised Controlled Trial (RCT) of the effects of a home-based exercise and support programme for people with dementia and their caregivers. The aim is to randomly assign 156 dyads (caregiver and dementia diagnosed person) to an intervention group or a comparison group. The experimental group receives a home programme in which exercise and support for the people with dementia and their caregivers are combined and integrated. The comparison group receives a minimal intervention. Primary outcomes are physical health (people with dementia) and mood (people with dementia and caregivers). In addition, to get more insight in the working components of the intervention and the impact of the intervention on the relationship of the dyads a qualitative sub-study is carried out.</p> <p>Discussion</p> <p>This study aims to contribute to an evidence-based treatment to reduce depressive symptoms among people with dementia and their caregivers independently living in the community.</p> <p>Trial Registration</p> <p>The study has been registered at the Netherlands National Trial Register (NTR), which is connected to the International Clinical Trials Registry Platform of the WHO. Trial number: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2040">NTR1802</a>.</p