A strategy to incorporate prior knowledge into correlation network cutoff selection
NATURE COMMUNICATIONS
Authors: Benedetti, Elisa; Pucic-Bakovic, Maja; Keser, Toma; Gerstner, Nathalie; Bueyuekoezkan, Mustafa; Stambuk, Tamara; Selman, Maurice H. J.; Rudan, Igor; Polasek, Ozren; Hayward, Caroline; Al-Amin, Hassen; Suhre, Karsten; Kastenmueller, Gabi; Lauc, Gordan; Krumsiek, Jan
Abstract
Correlation networks are frequently used to statistically extract biological interactions between omics markers. Network edge selection is typically based on the statistical significance of the correlation coefficients. This procedure, however, is not guaranteed to capture biological mechanisms. We here propose an alternative approach for network reconstruction: a cutoff selection algorithm that maximizes the overlap of the inferred network with available prior knowledge. We first evaluate the approach on IgG glycomics data, for which the biochemical pathway is known and well-characterized. Importantly, even in the case of incomplete or incorrect prior knowledge, the optimal network is close to the true optimum. We then demonstrate the generalizability of the approach with applications to untargeted metabolomics and transcriptomics data. For the transcriptomics case, we demonstrate that the optimized network is superior to statistical networks in systematically retrieving interactions that were not included in the biological reference used for optimization.
Serum IgG2 levels predict long-term protection following pneumococcal vaccination in systemic lupus erythematosus (SLE)
VACCINE
Authors: Gerard, Anne-Laure; Goulenok, Tiphaine; Bahuaud, Mathilde; Francois, Chrystelle; Aucouturier, Pierre; Moins-Teisserenc, Helene; Batteux, Frederic; Papo, Thomas; Sacre, Karim
Abstract
Systemic lupus erythematosus (SLE) patients are at risk for pneumococcal infection. Twenty-one consecutive SLE patients (40[25-75] years) received the sequential PCV13/PPSV23 vaccine and factors associated with long-term protection were analyzed. Immune protection, defined by an antigen-specific IgG concentration >= 1.3 mu g/mL for at least 70% of 7 pneumococcal serotypes was assessed at baseline, 2, 6, 12 and 36 months defining long-term protection. Only 10 patients showed pneumococcal immune protection 36 months after vaccination. Eleven (52.4%) patients had no long-term protection with a seroconversion that never or only transiently occurred. SLE disease features, treatment received and immunological characteristics did not differ between protected and unprotected patients except for the pre-vaccination IgG2 serum levels. Serum IgG2 level >2.125 mu g/ml showed a sensitivity of 100% and a specificity of 90.9% for long-term protection. Sequential pneumococcal vaccination conferred poor immune protection in SLE. Baseline IgG2 serum level identified patients able to benefit from pneumococcal vaccination. (c) 2020 Elsevier Ltd. All rights reserved.