Defining protein complexes is critical to virtually all aspects of cell biology. Two recent affinity purification/mass spectrometry studies in Saccharomyces cerevisiae have vastly increased the available protein interaction data. The practical utility of such high throughput interaction sets, however, is substantially decreased by the presence of false positives. Here we created a novel probabilistic metric that takes advantage of the high density of these data, including both the presence and absence of individual associations, to provide a measure of the relative confidence of each potential protein-protein interaction. This analysis largely overcomes the noise inherent in high throughput immunoprecipitation experiments. For example, of the 12,122 binary interactions in the general repository of interaction data (BioGRID) derived from these two studies, we marked 7504 as being of substantially lower confidence. Additionally, applying our metric and a stringent cutoff we identified a set of 9074 interactions (including 4456 that were not among the 12,122 interactions) with accuracy comparable to that of conventional small scale methodologies. Finally we organized proteins into coherent multisubunit complexes using hierarchical clustering. This work thus provides a highly accurate physical inter-
Purpose
To investigate the saturation-power dependence of amide proton transfer (APT)-weighted and nuclear Overhauser enhancement (NOE)-weighted image contrasts in a rat glioma model at 4.7 T.
Methods
9L tumor-bearing rats (n = 8) and fresh eggs (n = 4) were scanned on a 4.7-T animal MRI scanner. Z-spectra over an offset range of ±6 ppm were acquired with different saturation powers, followed by the magnetization transfer-ratio (MTR) asymmetry analyses around the water resonance.
Results
The NOE signal upfield from the water resonance (−2.5 to −5 ppm) was clearly visible at lower saturation powers (e.g., 0.6 μT) and was larger in the contralateral normal brain tissue than in the tumor. Conversely, the APT effect downfield from the water resonance was observed at relatively higher saturation powers (e.g., 2.1 μT) and was larger in the tumor than in the contralateral normal brain tissue. The NOE decreased the APT-weighted image signal, based on the MTR asymmetry analysis, but increased the APT-weighted image contrast between the tumor and contralateral normal brain tissue.
Conclusion
The APT and NOE image signals in tumor are maximized at different saturation powers. The saturation power of roughly 2 μT is ideal for APT-weighted imaging at clinical B0 field strengths.
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