Comparison of multiplex meta analysis techniques for understanding the acute rejection of solid organ transplants

<p>Abstract</p> <p>Background</p> <p>Combining the results of studies using highly parallelized measurements of gene expression such as microarrays and RNAseq offer unique challenges in meta analysis. Motivated by a need for a deeper understanding of organ transplant rejection, we combine the data from five separate studies to compare acute rejection versus stability after solid organ transplantation, and use this data to examine approaches to multiplex meta analysis.</p> <p>Results</p> <p>We demonstrate that a commonly used parametric effect size estimate approach and a commonly used non-parametric method give very different results in prioritizing genes. The parametric method providing a meta effect estimate was superior at ranking genes based on our gold-standard of identifying immune response genes in the transplant rejection datasets.</p> <p>Conclusion</p> <p>Different methods of multiplex analysis can give substantially different results. The method which is best for any given application will likely depend on the particular domain, and it remains for future work to see if any one method is consistently better at identifying important biological signal across gene expression experiments.</p

Lymphotoxin expression in human and murine renal allografts

The kidney is the most frequently transplanted solid organ. Recruitment of inflammatory cells, ranging from diffuse to nodular accumulations with defined microarchitecture, is a hallmark of acute and chronic renal allograft injury. Lymphotoxins (LTs) mediate the communication of lymphocytes and stromal cells and play a pivotal role in chronic inflammation and formation of lymphoid tissue. The aim of this study was to assess the expression of members of the LT system in acute rejection (AR) and chronic renal allograft injury such as transplant glomerulopathy (TG) and interstitial fibrosis/tubular atrophy (IFTA). We investigated differentially regulated components in transcriptomes of human renal allograft biopsies. By microarray analysis, we found the upregulation of LT beta, LIGHT, HVEM and TNF receptors 1 and 2 in AR and IFTA in human renal allograft biopsies. In addition, there was clear evidence for the activation of the NF kappa B pathway, most likely a consequence of LT beta receptor stimulation. In human renal allograft biopsies with transplant glomerulopathy (TG) two distinct transcriptional patterns of LT activation were revealed. By quantitative RT-PCR robust upregulation of LTa, LT beta and LIGHT was shown in biopsies with borderline lesions and AR. Immunohistochemistry revealed expression of LT beta in tubular epithelial cells and inflammatory infiltrates in transplant biopsies with AR and IFTA. Finally, activation of LT signaling was reproduced in a murine model of renal transplantation with AR. In summary, our results indicate a potential role of the LT system in acute renal allograft rejection and chronic transplant injury. Activation of the LT system in allograft rejection in rodents indicates a species independent mechanism. The functional role of the LT system in acute renal allograft rejection and chronic injury remains to be determined

High environmental niche overlap between the fungus Batrachochytrium dendrobatidis and invasive bullfrogs (Lithobates catesbeianus) enhance the potential of disease transmission in the Americas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Chytridiomycosis is linked to several amphibian population declines, including local extinctions. Besides this, it is already widespread over the globe, and one of the possible carriers is believed to be the American bullfrog. In order to assess whether the successful establishment of invasive bullfrog populations is associated with environmental suitability for Batrachochytrium dendrobatidis (Bd), we evaluated the close linkage between the fungus (Bd) and bullfrogs by measuring their environmental niche overlap. Our results indicate that Bd and bullfrogs largely overlap in their realized niches, wherein Bd occupies a larger climate space in which the bullfrogs' niche is nested. Therefore, our results strengthen the bullfrog carrier hypothesis. Besides this, we suggest that Bd can colonize areas adjacent to the bullfrogs' realized niche, infecting other species of native wild frogs. Central and South American governments must be aware of such problem and the international frog trade must be controlled to avoid further disease spreading.91178184Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Science Foundation (NSF)US Fish and Wildlife Service (USFWS)'Deutsche Bundesstiftung Umwelt' (DBU)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP