Highlights of B/D‐HPP and HPP Resource Pillar Workshops at 12th Annual HUPO World Congress of Proteomics

At the 12th Annual HUPO World Congress of Proteomics in Japan, the Human Proteome Project (HPP) presented 16 scientific workshop sessions. Here we summarize highlights of ten workshops from the Biology and Disease‐driven HPP (B/D‐HPP) teams and three from the HPP Resource Pillars. Highlights of the three Chromosome‐centric HPP sessions appeared in the many articles of the 2014 C‐HPP special issue of the Journal of Proteome Research 1 .     

New modes of data partitioning based on PARS peak alignment for improved multivariate biomarker/biopattern detection in 1H-NMR spectroscopic metabolic profiling of urine

This paper addresses the possibility of mathematically partition and process urine ¹H-NMR spectra to enhance the efficiency of the subsequent multivariate data analysis in the context of metabolic profiling of a toxicity study. We show that by processing the NMR data with the peak alignment using reduced set mapping (PARS) algorithm and the use of sparse representation of the data results in the information contained in the original NMR data being preserved with retained resolution but free of the problem of peak shifts. We can now describe a method for differential expression analysis of NMR spectra by using prior knowledge, i.e., the onset of dosing, a partitioning not possible to achieve using raw or bucketed data. In addition we also outline a scheme for soft removal of “biological noise” from the aligned data: exhaustive bio-noise subtraction (EBS). The result is a straightforward protocol for detection of peaks that appear as a consequence of the drug response. In other words, it is possible to elucidate peak origin, either from endogenous substances or from the administered drug/biomarkers. The partition of data originating from the normally regulating metabolome can, furthermore, be analyzed free of the superimposed biological noise. The proposed protocol results in enhanced interpretability of the processed data, i.e., a more refined metabolic trace, simplification of detection of consistent biomarkers, and a simplified search for metabolic end products of the administered drug.     

Characterization of the biochemical effects of 1-nitronaphthalene in rats using global metabolic profiling by NMR spectroscopy and pattern recognition

Abstract

Metabolic fingerprints, in the form of patterns of high-concentration endogenous metabolites, of 1-nitronaphthalene (NN)-induced lung toxicity have been elucidated in bronchoalveolar lavage fluid (BALF), urine, blood plasma, and intact lung and liver tissue using NMR spectroscopy-based metabolic profiling. A single dose of NN (75?mg?kg^?1) was administered orally to Sprague–Dawley rats. BALF and lung tissue were obtained 24?h after dosing from these animals and matched control rats post-mortem. High-resolution ¹H-NMR spectroscopy of BALF samples indicated that NN caused increases in concentrations of choline, amino acids (leucine, isoleucine and alanine) and lactate together with decreased concentrations of succinate, citrate, creatine, creatinine and glucose. In addition, the intact lung weights were higher in the NN-treated group (p<0.01), consistent with pulmonary oedema. The NMR-detected perturbations indicated that NN induces a perturbation in energy metabolism in both lung and liver tissue, as well as surfactant production and osmolyte levels in the lungs. As well as reporting the first NMR spectroscopic combined examination of BALF and intact lung, this study indicates that such holistic approaches to investigating mechanisms of lung toxicity may be of value in evaluating disease progression or the effects of therapeutic intervention in pulmonary conditions such as surfactant disorders or asthma.     

Electronic circular dichroism for the detection of microalbuminuria

Over the past decades, chiroptical spectroscopy has proved its incomparable ability to elucidate the structure and spatial arrangement of chiral molecules. Systematic analysis of biomolecules in the natural environment of biofluids, however, remains challenging. In this study, we used chiroptical spectroscopy to monitor urinary levels of human serum albumin. Not only severe proteinuria but even just a slightly increased urinary excretion of albumin (microalbuminuria) may indicate serious health complications, especially for diabetic individuals. Given the chiral nature of albumin and its typical spectral pattern, it may be easily observable by chiroptical spectroscopy, particularly electronic circular dichroism. The performed chiroptical analysis of urine not only allowed the detection of clinically confirmed microalbuminuria but was also able to reveal this pathological condition in cases beyond the diagnostic capability of common clinical procedures. Thus, our approach suggests that electronic circular dichroism is a useful tool for the fast and reliable qualitative monitoring of microalbuminuria with the potential for a quantitative analysis in the future.     

Simulation of Fluid Flow in a Channel Induced by Three Types of Fin-Like Motion

One of many interesting research activities in biofluidmechanics is dedicated to investigations of locomotion in water. Some of propulsion mechanisms observed in the underwater world are used in the development process of underwater autonomic vehicles （AUV）. In order to characterise several solutions according to their manoeuvrability, influence on the surrounding fluid and energetic efficiency, a detailed analysis of fin-like movement is indispensable. In the current paper an analysis of undulatory, oscillatory and combined fin-like movements by means of numerical simulation is carried out. The conservation equation of mass and the conservation equation of momentum axe solved with the Finite Volume Method （FWM） by use of the software CFX-10.0. The undulatory and oscillatory fin movements axe modelled with an equation that is implemented within an additional subroutine and joined with the main solver. N carried out in the computational domain, in which one fin is fixed in a flow-through water duct. Simulations axe carded out in the range of the Re number up to 105. The results show significant influence of applied fin motion on the velocity distribution in the surrounding fluid.     

Design of cellular porous biomaterials for wall shear stress criterion

The microfluidic environment provided by implanted prostheses has a decisive influence on the viability, proliferation and differentiation of cells. In bone tissue engineering, for instance, experiments have confirmed that a certain level of wall shear stress (WSS) is more advantageous to osteoblastic differentiation. This paper proposes a level‐set‐based topology optimization method to regulate fluidic WSS distribution for design of cellular biomaterials. The topological boundary of fluid phase is represented by a level‐set model embedded in a higher‐dimensional scalar function. WSS is determined by the computational fluid dynamics analysis in the scale of cellular base cells. To achieve a uniform WSS distribution at the solid–fluid interface, the difference between local and target WSS is taken as the design criterion, which determines the speed of the boundary evolution in the level‐set model. The examples demonstrate the effectiveness of the presented method and exhibit a considerable potential in the design optimization and fabrication of new prosthetic cellular materials for bioengineering applications. Biotechnol. Bioeng. 2010;107:737–746. © 2010 Wiley Periodicals, Inc.