Comparison of normalisation methods for surface-enhanced laser desorption and ionisation (SELDI) time-of-flight (TOF) mass spectrometry data

Background  

Mass spectrometry for biological data analysis is an active field of research, providing an efficient way of high-throughput proteome screening. A popular variant of mass spectrometry is SELDI, which is often used to measure sample populations with the goal of developing (clinical) classifiers. Unfortunately, not only is the data resulting from such measurements quite noisy, variance between replicate measurements of the same sample can be high as well. Normalisation of spectra can greatly reduce the effect of this technical variance and further improve the quality and interpretability of the data. However, it is unclear which normalisation method yields the most informative result.     

HAT: Hypergeometric Analysis of Tiling-arrays with application to promoter-GeneChip data

Background  

Tiling-arrays are applicable to multiple types of biological research questions. Due to its advantages (high sensitivity, resolution, unbiased), the technology is often employed in genome-wide investigations. A major challenge in the analysis of tiling-array data is to define regions-of-interest, i.e., contiguous probes with increased signal intensity (as a result of hybridization of labeled DNA) in a region. Currently, no standard criteria are available to define these regions-of-interest as there is no single probe intensity cut-off level, different regions-of-interest can contain various numbers of probes, and can vary in genomic width. Furthermore, the chromosomal distance between neighboring probes can vary across the genome among different arrays.     

Indocyanine green pharmacokinetics in the rabbit

In a Latin square design, nine New Zealand white male rabbits (2.8-4.8 kg) each received intravenous indocyanine green (ICG) in doses of 2.5, 12.5, and 25 mg/kg. A period of 4 weeks separated consecutive experiments. A specific high-pressure liquid chromatographic (HPLC) assay and the traditional spectrophotometric (SPEC) method were used to monitor plasma ICG. The analyses demonstrated the ambiguous nature of the SPEC assay, and the HPLC procedure pointed to the presence of an unidentified ICG metabolite. Dose-dependent ICG disposition was evident from the ANOVA of the mean (+/- SD) clearances, namely, 17.09 (7.35), 4.50 (0.82), and 2.27 (0.57) mL X min-1 X kg-1 for the aforementioned doses, respectively. Analysis of variance of the clearances also demonstrated a significant ordering effect suggesting cumulative ICG toxicity. The mean ICG profiles for the three doses accorded with a novel three-compartment model containing two ICG distributional spaces in addition to a compartment (liver) responsible for ICG elimination from the circulation. A saturable uptake process into the eliminating compartment (Vmax = 0.93 mg X kg-1 X min-1; Km = 31.9 mg/L) accounted for the dose-dependent features. Additional studies in four unanesthetized rabbits with chronically catheterized bile ducts revealed no disparity between the SPEC and HPLC analyses of biliary ICG. The mean (+/- SD) ICG recovery in bile following an intravenous dose of about 12.5 mg/kg was 59.8 (16.3)%.