Identifying Biomarkers from Mass Spectrometry Data with Ordinal Outcome

In recent years, there has been an increased interest in using protein mass spectroscopy to identify molecular markers that discriminate diseased from healthy individuals. Existing methods are tailored towards classifying observations into nominal categories. Sometimes, however, the outcome of interest may be measured on an ordered scale. Ignoring this natural ordering results in some loss of information. In this paper, we propose a Bayesian model for the analysis of mass spectrometry data with ordered outcome. The method provides a unified approach for identifying relevant markers and predicting class membership. This is accomplished by building a stochastic search variable selection method within an ordinal outcome model. We apply the methodology to mass spectrometry data on ovarian cancer cases and healthy individuals. We also utilize wavelet-based techniques to remove noise from the mass spectra prior to analysis. We identify protein markers associated with being healthy, having low grade ovarian cancer, or being a high grade case. For comparison, we repeated the analysis using conventional classification procedures and found improved predictive accuracy with our method

Thrombosis is associated with inferior survival in multiple myeloma.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Patients with multiple myeloma are at an increased risk of venous thromboembolism and arterial thrombosis. We assessed the impact of venous and arterial thrombosis on survival in a population-based study of 9,399 multiple myeloma patients diagnosed in Sweden from 1987 to 2005. We found multiple myeloma patients with venous thromboembolism to have a higher mortality at 1-, 5-, and 10-years of follow up compared with those without, with hazard ratios of 2.9 (95% confidence interval (CI) 2.4-3.5), 1.6 (95% CI: 1.5-1.8), and 1.6 (95% CI: 1.4-1.7), respectively. There was an increase in risk of death among multiple myeloma patients with arterial thrombosis, with hazard ratios of 3.4 (95% CI: 3.0-3.8), 2.2 (95% CI: 2.0-2.3), and 2.1 (95% CI: 1.9-2.1), respectively. In landmark analyses at six months, early arterial but not venous thromboembolism was associated with a higher risk of death. Thus, in contrast to prior smaller studies, we found the development of thrombosis to be associated with significantly poorer survival. The prevention of thrombosis in multiple myeloma is an important goal in the management of these patients.regional agreement on medical training and clinical research (ALF) between Stockholm County Council regional agreement on medical training and clinical research (ALF) between Karolinska Institutet Cancer Society in Stockholm Intramural Research Program of the NIH, NC

Menopausal hormone therapy and risk of biliary tract cancers

Funding: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The funders had no role in the conduct of this research.Peer reviewedPostprintsupplementary_dat

A population-based study of Kaposi Sarcoma-associated herpesvirus seropositivity in Uganda using principal components analysis

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity is associated with sexual, environmental, and socioeconomic exposures. Whether these characteristics are independent risk factors is uncertain because of reliance on selected high-risk or hospital-based populations and incomplete adjustment for confounding. Therefore, we evaluated risk factors for KSHV seropositivity in a population-based study in Uganda using principal components analysis (PCA). METHODS: The study population comprised 2,681 individuals randomly selected from a nationally-representative population-based HIV/AIDS sero-behavioral survey conducted in 2004/05. Questionnaire and laboratory data (97 variables) were transformed into a smaller set of uncorrelated variables using PCA. Multivariable logistic regression models were fitted to estimate odds ratios and 95% confidence intervals for the association between components and KSHV seropositivity. RESULTS: Data were reduced to three principal components (PCs) labeled as Sexual behavioral, Socioeconomic, and Knowledge PCs. In crude analysis, KSHV seropositivity was associated with the Knowledge (p(trend) = 0.012) and Socioeconomic components (p(trend) = 0.0001), but not with the Sexual-behavioral component (p(trend) = 0.066). KSHV seropositivity was associated with the Socioeconomic PC (p(trend) = 0.037), but not with the Sexual-behavioral and Knowledge PCs, in the models including PCs, age, gender and geographic region. CONCLUSIONS: Our results fit with the view that in Uganda socioeconomic characteristic may influence KSHV seropositivity. Conversely, the results fit with the interpretation that in Uganda sexual-behavioral characteristics, if relevant, contribute minimally

A population-based study of Kaposi Sarcoma-associated herpesvirus seropositivity in Uganda using principal components analysis

Abstract Background Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity is associated with sexual, environmental, and socioeconomic exposures. Whether these characteristics are independent risk factors is uncertain because of reliance on selected high-risk or hospital-based populations and incomplete adjustment for confounding. Therefore, we evaluated risk factors for KSHV seropositivity in a population-based study in Uganda using principal components analysis (PCA). Methods The study population comprised 2,681 individuals randomly selected from a nationally-representative population-based HIV/AIDS sero-behavioral survey conducted in 2004/05. Questionnaire and laboratory data (97 variables) were transformed into a smaller set of uncorrelated variables using PCA. Multivariable logistic regression models were fitted to estimate odds ratios and 95% confidence intervals for the association between components and KSHV seropositivity. Results Data were reduced to three principal components (PCs) labeled as Sexual behavioral, Socioeconomic, and Knowledge PCs. In crude analysis, KSHV seropositivity was associated with the Knowledge (p trend  = 0.012) and Socioeconomic components (p trend  = 0.0001), but not with the Sexual-behavioral component (p trend  = 0.066). KSHV seropositivity was associated with the Socioeconomic PC (p trend  = 0.037), but not with the Sexual-behavioral and Knowledge PCs, in the models including PCs, age, gender and geographic region. Conclusions Our results fit with the view that in Uganda socioeconomic characteristic may influence KSHV seropositivity. Conversely, the results fit with the interpretation that in Uganda sexual-behavioral characteristics, if relevant, contribute minimally.http://deepblue.lib.umich.edu/bitstream/2027.42/112399/1/13027_2012_Article_423.pd

Association between aspirin use and biliary tract cancer survival

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Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men