ProSight PTM 2.0: improved protein identification and characterization for top down mass spectrometry

ProSight PTM 2.0 (http://prosightptm2.scs.uiuc.edu) is the next generation of the ProSight PTM web-based system for the identification and characterization of proteins using top down tandem mass spectrometry. It introduces an entirely new data-driven interface, integrated Sequence Gazer for protein characterization, support for fixed modifications, terminal modifications and improved support for multiple precursor ions (multiplexing). Furthermore, it supports data import and export for local analysis and collaboration

Discovery of protein–DNA interactions by penalized multivariate regression

Discovering which regulatory proteins, especially transcription factors (TFs), are active under certain experimental conditions and identifying the corresponding binding motifs is essential for understanding the regulatory circuits that control cellular programs. The experimental methods used for this purpose are laborious. Computational methods have been proven extremely effective in identifying TF-binding motifs (TFBMs). In this article, we propose a novel computational method called MotifExpress for discovering active TFBMs. Unlike existing methods, which either use only DNA sequence information or integrate sequence information with a single-sample measurement of gene expression, MotifExpress integrates DNA sequence information with gene expression measured in multiple samples. By selecting TFBMs that are significantly associated with gene expression, we can identify active TFBMs under specific experimental conditions and thus provide clues for the construction of regulatory networks. Compared with existing methods, MotifExpress substantially reduces the number of spurious results. Statistically, MotifExpress uses a penalized multivariate regression approach with a composite absolute penalty, which is highly stable and can effectively find the globally optimal set of active motifs. We demonstrate the excellent performance of MotifExpress by applying it to synthetic data and real examples of Saccharomyces cerevisiae. MotifExpress is available at http://www.stat.illinois.edu/~pingma/MotifExpress.htm

Review of advanced catheter technologies in radiation oncology brachytherapy procedures

Jun Zhou,1,2 Leonid Zamdborg,1 Evelyn Sebastian1 1Department of Radiation Oncology, Beaumont Health System, 2Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA Abstract: The development of new catheter and applicator technologies in recent years has significantly improved treatment accuracy, efficiency, and outcomes in brachytherapy. In this paper, we review these advances, focusing on the performance of catheter imaging and reconstruction techniques in brachytherapy procedures using magnetic resonance images and electromagnetic tracking. The accuracy of catheter reconstruction, imaging artifacts, and other notable properties of plastic and titanium applicators in gynecologic treatments are reviewed. The accuracy, noise performance, and limitations of electromagnetic tracking for catheter reconstruction are discussed. Several newly developed applicators for accelerated partial breast irradiation and gynecologic treatments are also reviewed. New hypofractionated high dose rate treatment schemes in prostate cancer and accelerated partial breast irradiation are presented. Keywords: catheter technologies, catheter reconstruction, electromagnetic tracking, hypofractionated high dose rate treatment, accelerated partial breast irradiatio

Quantitative Peptidomics for Discovery of Circadian-Related Peptides from the Rat Suprachiasmatic Nucleus

In mammals the suprachiasmatic nucleus (SCN), the master circadian clock, is sensitive to light input via the optic chiasm and synchronizes many daily biological rhythms. Here we explore variations in the expression levels of neuropeptides present in the SCN of rats using a label-free quantification approach that is based on integrating peak intensities between daytime, Zeitgeber time (ZT) 6, and nighttime, ZT 18. From nine analyses comparing the levels between these two time points, 10 endogenous peptides derived from eight prohormones exhibited significant differences in their expression levels (adjusted <i>p</i>-value <0.05). Of these, seven peptides derived from six prohormones, including GRP, PACAP, and CART, exhibited ≥30% increases at ZT 18, and the VGRPE­WWMDYQ peptide derived from proenkephalin A showed a >50% increase at nighttime. Several endogenous peptides showing statistically significant changes in this study have not been previously reported to alter their levels as a function of time of day, nor have they been implicated in prior functional SCN studies. This information on peptide expression changes serves as a resource for discovering unknown peptide regulators that affect circadian rhythms in the SCN

Comparing Label-Free Quantitative Peptidomics Approaches to Characterize Diurnal Variation of Peptides in the Rat Suprachiasmatic Nucleus

Mammalian circadian rhythm is maintained by the suprachiasmatic nucleus (SCN) via an intricate set of neuropeptides and other signaling molecules. In this work, peptidomic analyses from two times of day were examined to characterize variation in SCN peptides using three different label-free quantitation approaches: spectral count, spectra index and SIEVE. Of the 448 identified peptides, 207 peptides were analyzed by two label-free methods, spectral count and spectral index. There were 24 peptides with significant (adjusted <i>p</i>-value < 0.01) differential peptide abundances between daytime and nighttime, including multiple peptides derived from secretogranin II, cocaine and amphetamine regulated transcript, and proprotein convertase subtilisin/kexin type 1 inhibitor. Interestingly, more peptides were analyzable and had significantly different abundances between the two time points using the spectral count and spectral index methods than with a prior analysis using the SIEVE method with the same data. The results of this study reveal the importance of using the appropriate data analysis approaches for label-free relative quantitation of peptides. The detection of significant changes in so rich a set of neuropeptides reflects the dynamic nature of the SCN and the number of influences such as feeding behavior on circadian rhythm. Using spectral count and spectral index, peptide level changes are correlated to time of day, suggesting their key role in circadian function