An expert-based system to predict population survival rate from health data.

Timely detection and understanding of causes for population decline are essential for effective wildlife management and conservation. Assessing trends in population size has been the standard approach, but we propose that monitoring population health could prove more effective. We collated data from 7 bottlenose dolphin (Tursiops truncatus) populations in the southeastern United States to develop a method for estimating survival probability based on a suite of health measures identified by experts as indices for inflammatory, metabolic, pulmonary, and neuroendocrine systems.

Spatial distributions of phosphorylated membrane proteins aquaporin 0 and MP20 across young and aged human lenses.

In the human ocular lens it is now realized that post-translational modifications can alter protein function and/or localization in fiber cells that no longer synthesize proteins. The specific sites of post-translational modification to the abundant ocular lens membrane proteins AQP0 and MP20 have been previously identified and their functional effects are emerging. To further understand how changes in protein function and/or localization induced by these modifications alter lens homeostasis, it is necessary to determine the spatial distributions of these modifications across the lens.

The application of Gaussian mixture models for signal quantification in MALDI-TOF mass spectrometry of peptides.

Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled with stable isotope standards (SIS) has been used to quantify native peptides. This peptide quantification by MALDI-TOF approach has difficulties quantifying samples containing peptides with ion currents in overlapping spectra. In these overlapping spectra the currents sum together, which modify the peak heights and make normal SIS estimation problematic.

Imbalanced expression of Vcan mRNA splice form proteins alters heart morphology and cellular protein profiles.

The fundamental importance of the proteoglycan versican to early heart formation was clearly demonstrated by the Vcan null mouse called heart defect (hdf). Total absence of the Vcan gene halts heart development at a stage prior to the heart's pulmonary/aortic outlet segment growth. This creates a problem for determining the significance of versican's expression in the forming valve precursors and vascular wall of the pulmonary and aortic roots.

Revealing functionally coherent subsets using a spectral clustering and an information integration approach.

Background: Contemporary high-throughput analyses often produce lengthy lists of genes or proteins. It is desirable to divide the genes into functionally coherent subsets for further investigation, by integrating heterogeneous information regarding the genes. Here we report a principled approach for managing and integrating multiple data sources within the framework of graph-spectrum analysis in order to identify coherent gene subsets.

Network modeling reveals steps in angiotensin peptide processing.

New insights into the intrarenal renin-angiotensin (Ang) system have modified our traditional view of the system. However, many finer details of this network of peptides and associated peptidases remain unclear. We hypothesized that a computational systems biology approach, applied to peptidomic data, could help to unravel the network of enzymatic conversions.

Forensic identification of seal oils using lipid profiles and statistical models.

Seal blubber oils are used as a source of omega-3 polyunsaturated fatty acids in Canada but prohibited in the United States and (FA) European Union. Thus, a reliable method is needed to identify oils originating from seals versus fish. Two lipid profiling methods, fatty acid analysis using gas chromatography and triacylglycerol (TAG) analysis using liquid chromatography and mass spectrometry, were applied with statistical models to discriminate commercial oils and blubber samples harvested from marine fish and seals.

AKAP signaling in reinstated cocaine seeking revealed by iTRAQ proteomic analysis.

To identify candidate proteins in the nucleus accumbens (NAc) as potential pharmacotherapeutic targets for treating cocaine addition, an 8-plex iTRAQ (isobaric tag for relative and absolute quantitation) proteomic screen was performed using NAc tissue obtained from rats trained to self-administer cocaine followed by extinction training. Compared with yoked-saline controls, 42 proteins in a postsynaptic density (PSD)-enriched subfraction of the NAc from cocaine-trained animals were identified as significantly changed. Among proteins of interest whose levels were identified as increased was AKAP79/150, the rat ortholog of human AKAP5, a PSD scaffolding protein that localizes signaling molecules to the synapse.

Biochemical systems analysis of signaling pathways to understand fungal pathogenicity.

Over the past decade, researchers have recognized the need to study biological systems as integrated systems. While the reductionist approaches of the past century have made remarkable advances of our understanding of life, the next phase of understanding comes from systems-level investigations. Additionally, biology has become a data-intensive field of research.

Tight binding of proteins to membranes from older human cells.

The lens is an ideal model system for the study of macromolecular aging and its consequences for cellular function, since there is no turnover of lens fibre cells. To examine biochemical processes that take place in the lens and that may also occur in other long-lived cells, membranes were isolated from defined regions of human lenses that are synthesised at different times during life, and assayed for the presence of tightly bound cytosolic proteins using quantitative iTRAQ proteomics technology. A majority of lens beta crystallins and all gamma crystallins became increasingly membrane bound with age, however, the chaperone proteins alpha A and alpha B crystallin, as well as the thermally-stable protein, βB2 crystallin, did not.

Matrix-assisted laser desorption/ionization tissue profiling of secretoneurin in the nucleus accumbens shell from cocaine-sensitized rats.

Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging.

iQuantitator: a tool for protein expression inference using iTRAQ.

Background: Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) [Applied Biosystems] have seen increased application in differential protein expression analysis. To facilitate the growing need to analyze iTRAQ data, especially for cases involving multiple iTRAQ experiments, we have developed a modeling approach, statistical methods, and tools for estimating the relative changes in protein expression under various treatments and experimental conditions.

Results: This modeling approach provides a unified analysis of data from multiple iTRAQ experiments and links the observed quantity (reporter ion peak area) to the experiment design and the calculated quantity of interest (treatment-dependent protein and peptide fold change) through an additive model under log transformation.

Quantification of protein expression changes in the aging left ventricle of Rattus norvegicus.

As the heart ages, electrophysiological and biochemical changes can occur, and the ventricle in many cases loses distensibility, impairing diastolic function. How the proteomic signature of the aged ventricle is unique in comparison to young hearts is still under active investigation. We have undertaken a quantitative proteomics study of aging left ventricles (LVs) utilizing the isobaric Tagging for Relative and Absolute Quantification (iTRAQ) methodology.

A statistical model for iTRAQ data analysis.

We describe biological and experimental factors that induce variability in reporter ion peak areas obtained from iTRAQ experiments. We demonstrate how these factors can be incorporated into a statistical model for use in evaluating differential protein expression and highlight the benefits of using analysis of variance to quantify fold change. We demonstrate the model's utility based on an analysis of iTRAQ data derived from a spike-in study.

Concentration-dependent effects on the rapid and efficient activation of the MAP kinase signaling cascade.

Modern proteomic techniques are making it possible to identify and quantitate increasingly complex mixtures of cellular proteins. Translating the relative expression measurements collected in these experiments into an understanding of the associated physiological phenomena continues to be a challenge for the field of systems biology. We demonstrate how methods of mathematical and computational systems biology permit us to proffer explanations for the observed concentration ranges of signaling components found in the highly conserved mitogen-activated protein kinase (MAPK) cascade.

The potential for signal integration and processing in interacting MAP kinase cascades.

The cellular response to environmental stimuli requires biochemical information processing through which sensory inputs and cellular status are integrated and translated into appropriate responses by way of interacting networks of enzymes. One such network, the mitogen-activated protein (MAP) kinase cascade is a highly conserved signal transduction module that propagates signals from cell surface receptors to various cytosolic and nuclear targets by way of a phosphorylation cascade. We have investigated the potential for signal processing within a network of interacting feed-forward kinase cascades typified by the MAP kinase cascade.

Computation and analysis of time-dependent sensitivities in Generalized Mass Action systems.

Understanding biochemical system dynamics is becoming increasingly important for insights into the functioning of organisms and for biotechnological manipulations, and additional techniques and methods are needed to facilitate investigations of dynamical properties of systems. Extensions to the method of Ingalls and Sauro, addressing time-dependent sensitivity analysis, provide a new tool for executing such investigations. We present here the results of sample analyses using time-dependent sensitivities for three model systems taken from the literature, namely an anaerobic fermentation pathway in yeast, a negative feedback oscillator modeling cell-cycle phenomena, and the Mitogen Activated Protein (MAP) kinase cascade.

Improved methods for the mathematically controlled comparison of biochemical systems.

The method of mathematically controlled comparison provides a structured approach for the comparison of alternative biochemical pathways with respect to selected functional effectiveness measures. Under this approach, alternative implementations of a biochemical pathway are modeled mathematically, forced to be equivalent through the application of selected constraints, and compared with respect to selected functional effectiveness measures. While the method has been applied successfully in a variety of studies, we offer recommendations for improvements to the method that (1) relax requirements for definition of constraints sufficient to remove all degrees of freedom in forming the equivalent alternative, (2) facilitate generalization of the results thus avoiding the need to condition those findings on the selected constraints, and (3) provide additional insights into the effect of selected constraints on the functional effectiveness measures.