Purpose
In mass spectrometry (MS)‐based studies to discover urinary protein biomarkers, an important question is how to analyze the data to find the most promising potential biomarkers to be advanced ...to large‐scale validation studies. Here, we describe a “systems biology‐based” approach to address this question.
Experimental design
We analyzed large‐scale liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) data of urinary exosomes from renal allograft recipients with biopsy‐proven evidence of immunological rejection or tubular injury (TI). We asked whether bioinformatic analysis of urinary exosomal proteins can identify biological‐process based protein groups that correlate with biopsy findings and whether the protein groups fit with general knowledge of the pathophysiological mechanisms involved.
Results
LC‐MS/MS analysis of urinary exosomal proteomes identified more than 1000 proteins in each pathologic group. These protein lists were analyzed computationally to identify the Biological Process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway terms that are significantly associated with each pathological group. Among the most informative terms for each group were: “sodium ion transport” for TI; “immune response” for all rejection; “epithelial cell differentiation” for cell‐mediated rejection; and “acute inflammatory response” for antibody‐mediated rejection. Based on these terms, candidate biomarkers were identified using a novel strategy to allow a dichotomous classification between different pathologic categories.
Conclusions and clinical relevance
The terms and candidate biomarkers identified make rational connections to pathophysiological mechanisms, suggesting that the described bioinformatic approach will be useful in advancing large‐scale biomarker identification studies toward a validation phase.
Urea recycling and counter-current exchange within the renal tubular, vascular and interstitial compartments help maintain high levels of this solute in the renal medulla, that are crucial for the ...production of concentrated urine. The role of urea in physiological and pathological conditions is still unclear, although new information is becoming available. Several urea transporters have been identified that mediate facilitated transport of urea across biological membranes in the mammalian kidney, in amphibians, and in elasmobranchs. Evidence that urea transporters may be expressed in other mammalian organs is also beginning to emerge. The mechanisms involved in the regulation of urea transport are incompletely understood. In this respect, the structural and functional characterization of individual transporters is providing the basis to identify specific regulatory factors. Urea can be viewed as a perturbing osmolyte in the renal inner medulla, and the mechanisms of adaptation of renal cells to high concentration of this destabilizing solute are being investigated. Urea-specific signaling pathways have been identified, that could contribute to clarify how cells handle urea.
The next generation of high energy physics (HEP) experiments requires a GRID approach to a distributed computing system: the key concept is the Virtual ORGANISATION (VO), a group of distributed users ...with a common goal and the will to share their resources.
A similar approach, applied to a group of hospitals that joined the GPCALMA project (Grid Platform for Computer Assisted Library for MAmmography), will allow common screening programs for early diagnosis of breast and, in the future, lung cancer. The application code makes use of neural networks for the image analysis and is useful in improving the radiologists' diagnostic performance. GRID services allow remote image analysis and interactive online diagnosis, with a potential for a relevant reduction of the delays presently associated with screening programs.
A prototype of the system, based on AliEn GRID Services 1, is already available, with a central server running common services 2 and several clients connecting to it. Mammograms can be acquired in any location; the related information required to select and access them at any time is stored in a common service called Data Catalogue, which can be queried by any client. Thanks to the PROOF facility 3, the result of a query can be used as input for analysis algorithms, which are executed on the nodes where the input images are stored,. The selected approach avoids data transfers for all the images with a negative diagnosis and allows an almost real time diagnosis for the set of images with high cancer probability.
Experiment E835 at Fermilab Garzoglio, G.; Gollwitzer, K.; Hahn, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2004, Letnik:
519, Številka:
3
Journal Article
Recenzirano
We provide a comprehensive description of experiment E835 at Fermilab, a high-precision experimental study of charmonium bound states. The
c
̄
c
states are formed in
p
̄
p
annihilations of cooled ...antiprotons stored in the Fermilab Antiproton Accumulator using a dense internal hydrogen gas-jet target. We describe the experimental strategies adopted for detecting the tiny
c
̄
c
resonant signals in the huge non-resonant hadronic background, and for measuring resonance parameters with high precision.
GPCALMA: a grid approach to mammographic screening Bagnasco, S.; Bottigli, U.; Cerello, P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2004, Letnik:
518, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The next generation of High Energy Physics (HEP) experiments requires a GRID approach to a distributed computing system and the associated data management: the key concept is the Virtual ...Organisation, a group of geographically distributed users with a common goal and the will to share their resources. A similar approach is being applied to a group of Hospitals which joined the GPCALMA project which will allow common screening programs for early diagnosis of breast and, in the future, lung cancer. HEP techniques come into play in writing the application code, which makes use of neural networks for the image analysis and shows performances similar to radiologists in the diagnosis. GRID technologies will allow remote image analysis and interactive online diagnosis, with a relevant reduction of the delays presently associated with screening programs.
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