Baseline correction for NMR spectroscopic metabolomics data analysis.

BackgroundWe propose a statistically principled baseline correction method, derived from a parametric smoothing model. It uses a score function to describe the key features of baseline distortion and constructs an optimal baseline curve to maximize it. The parameters are determined automatically by using LOWESS (locally weighted scatterplot smoothing) regression to estimate the noise variance.ResultsWe tested this method on 1D NMR spectra with different forms of baseline distortions, and demonstrated that it is effective for both regular 1D NMR spectra and metabolomics spectra with over-crowded peaks.ConclusionCompared with the automatic baseline correction function in XWINNMR 3.5, the penalized smoothing method provides more accurate baseline correction for high-signal density metabolomics spectra

On the cumulants of affine equivariant estimators in elliptical families

AbstractGiven a statistical model for data which take values in Rd and have elliptically distributed errors, and affine equivariant estimators μ̂ and μ̂ of a mean vector in Rd⊗Rn and a d × d scatter matrix, expressions are given for the covarances of the estimators in terms of their expectations and some unknown constants that depend on the model and the estimator. Higher order cumulants are also developed. These results place considerable constraints on the possible cumulants of μ̂ and μ̂, as wel as those of estimators of higher order behavior such as multivariate skewness and kurtosis. These expressions are obtained using tensor methods

Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

During course of this project, we have worked in several areas relevant to low-dose ionizing radiation. Using gene expression to measure biological response, we have examined the response of human skin exposed in-vivo to radation, human skin exposed ex-vivo to radiation, and a human-skin model exposed to radiation. We have learned a great deal about the biological response of human skin to low-dose ionizing radiation

Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes.

ObjectiveWe examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD).Research design and methodsUsing targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses.ResultsAt baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m2 and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29-0.87]) and death (HR [95% CI] 0.56 [0.34-0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41-0.79] and 0.66 [0.44-0.97], respectively); higher urine factor H-related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05-2.48]) in fully adjusted models.ConclusionsIn a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death

Deducing signaling pathways from parallel actions of arsenite and antimonite in human epidermal keratinocytes.

Inorganic arsenic oxides have been identified as carcinogens in several human tissues, including epidermis. Due to the chemical similarity between trivalent inorganic arsenic (arsenite) and antimony (antimonite), we hypothesized that common intracellular targets lead to similarities in cellular responses. Indeed, transcriptional and proteomic profiling revealed remarkable similarities in differentially expressed genes and proteins resulting from exposure of cultured human epidermal keratinocytes to arsenite and antimonite in contrast to comparisons of arsenite with other metal compounds. These data were analyzed to predict upstream regulators and affected signaling pathways following arsenite and antimonite treatments. A majority of the top findings in each category were identical after treatment with either compound. Inspection of the predicted upstream regulators led to previously unsuspected roles for oncostatin M, corticosteroids and ephrins in mediating cellular response. The influence of these predicted mediators was then experimentally verified. Together with predictions of transcription factor effects more generally, the analysis has led to model signaling networks largely accounting for arsenite and antimonite action. The striking parallels between responses to arsenite and antimonite indicate the skin carcinogenic risk of exposure to antimonite merits close scrutiny