Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Local Renyi entropic profiles of DNA sequences

<p>Abstract</p> <p>Background</p> <p>In a recent report the authors presented a new measure of continuous entropy for DNA sequences, which allows the estimation of their randomness level. The definition therein explored was based on the Rényi entropy of probability density estimation (pdf) using the Parzen's window method and applied to Chaos Game Representation/Universal Sequence Maps (CGR/USM). Subsequent work proposed a fractal pdf kernel as a more exact solution for the iterated map representation. This report extends the concepts of continuous entropy by defining DNA sequence entropic profiles using the new pdf estimations to refine the density estimation of motifs.</p> <p>Results</p> <p>The new methodology enables two results. On the one hand it shows that the entropic profiles are directly related with the statistical significance of motifs, allowing the study of under and over-representation of segments. On the other hand, by spanning the parameters of the kernel function it is possible to extract important information about the scale of each conserved DNA region. The computational applications, developed in Matlab m-code, the corresponding binary executables and additional material and examples are made publicly available at <url>http://kdbio.inesc-id.pt/~svinga/ep/</url>.</p> <p>Conclusion</p> <p>The ability to detect local conservation from a scale-independent representation of symbolic sequences is particularly relevant for biological applications where conserved motifs occur in multiple, overlapping scales, with significant future applications in the recognition of foreign genomic material and inference of motif structures.</p

Post-translational modifications and mass spectrometry detection

In this review, we provide a comprehensive bibliographic overview of the role of mass spectrometry and the recent technical developments in the detection of post-translational modifications (PTMs). We briefly describe the principles of mass spectrometry for detecting PTMs and the protein and peptide enrichment strategies for PTM analysis, including phosphorylation, acetylation and oxidation. This review presents a bibliographic overview of the scientific achievements and the recent technical development in the detection of PTMs is provided. In order to ascertain the state of the art in mass spectrometry and proteomics methodologies for the study of PTMs, we analyzed all the PTM data introduced in the Universal Protein Resource (UniProt) and the literature published in the last three years. The evolution of curated data in UniProt for proteins annotated as being post-translationally modified is also analyzed. Additionally, we have undertaken a careful analysis of the research articles published in the years 2010 to 2012 reporting the detection of PTMs in biological samples by mass spectrometry. © 2013 Elsevier Inc

No age limit for radical radiotherapy in head and neck tumours

The elderly are often treated less aggressively in an attempt to preserve their quality of Life with regards to toxicity. However, there are few data regarding the acute and late toxicity of radiotherapy (RT) in elderly patients. From February 1980 to March 1995, 1589 patients with head and neck cancers who enrolled in EORTC trials received RT and were available for analysis on RT toxicity. Patients over 65 years of age were in excess of 20%. Data regarding age and acute objective mucosal reactions were available for 1307 patients and 1288 had toxicity greater than or equal to grade 1. Age and acute functional mucosal reactions were registered for 838 patients and 824 patients had toxicity greater than or equal to grade 1. Bodyweight alteration during treatment was available in 1252 patients; it increased in 153 patients and decreased in 1099 patients. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first- and second-line treatments. 749 patients were available for analysis of which 646 had late toxicity grade greater than or equal to 1. Survival and toxicity were examined in different age ranges from 50 to 75 years and over. There was no significant difference in survival between each age group. A trend test was performed to assess any correlation between age and the acute occurring toxicity. There was no significant difference in acute objective mucosal reactions (P = 0.1) and in weight loss > 10% (P = 0.441). In contrast, older patients had more severe (grade 3 and 4) functional acute toxicity (P < 0.001) than younger patients. We evaluated the probability of late toxicity occurrence in relation to time with the Kaplan-Meier method and the logrank test in each age group. Eighteen per cent of patients were free of late effects at 5 years, the logrank test showing no significant difference between ages (P = 0.84). In conclusion, chronological age is irrelevant for therapeutic decisions. Copyright (C) 1996 Elsevier Science Lt

Associated average charged particle multiplicities in K+pK^+p interactions at 32 GeV/c

The average charged particle multiplicities, 〈nR(MX2)〉, in the reactions K+p → π-X and K+p → K0X at 32 GeV/c are studied as functions of the mass squared MX2 of the "associated" system X. A comparison with the corresponding results obtained at lower incident momenta is presented. © 1976.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Critical assessment of alignment procedures for LC-MS proteomics and metabolomics measurements

<p>Abstract</p> <p>Background</p> <p>Liquid chromatography coupled to mass spectrometry (LC-MS) has become a prominent tool for the analysis of complex proteomics and metabolomics samples. In many applications multiple LC-MS measurements need to be compared, e. g. to improve reliability or to combine results from different samples in a statistical comparative analysis. As in all physical experiments, LC-MS data are affected by uncertainties, and variability of retention time is encountered in all data sets. It is therefore necessary to estimate and correct the underlying distortions of the retention time axis to search for corresponding compounds in different samples. To this end, a variety of so-called <it>LC-MS map alignment algorithms </it>have been developed during the last four years. Most of these approaches are well documented, but they are usually evaluated on very specific samples only. So far, no publication has been assessing different alignment algorithms using a standard LC-MS sample along with commonly used quality criteria.</p> <p>Results</p> <p>We propose two LC-MS proteomics as well as two LC-MS metabolomics data sets that represent typical alignment scenarios. Furthermore, we introduce a new quality measure for the evaluation of LC-MS alignment algorithms. Using the four data sets to compare six freely available alignment algorithms proposed for the alignment of metabolomics and proteomics LC-MS measurements, we found significant differences with respect to alignment quality, running time, and usability in general.</p> <p>Conclusion</p> <p>The multitude of available alignment methods necessitates the generation of standard data sets and quality measures that allow users as well as developers to benchmark and compare their map alignment tools on a fair basis. Our study represents a first step in this direction. Currently, the installation and evaluation of the "correct" parameter settings can be quite a time-consuming task, and the success of a particular method is still highly dependent on the experience of the user. Therefore, we propose to continue and extend this type of study to a community-wide competition. All data as well as our evaluation scripts are available at <url>http://msbi.ipb-halle.de/msbi/caap</url>.</p